Langbahn Team – Weltmeisterschaft

5-HT2A receptor

HTR2A
Identifiers
AliasesHTR2A, 5-HT2A, HTR2, 5-hydroxytryptamine receptor 2A
External IDsOMIM: 182135; MGI: 109521; HomoloGene: 68073; GeneCards: HTR2A; OMA:HTR2A - orthologs
Orthologs
SpeciesHumanMouse
Entrez

3356

15558

Ensembl

ENSG00000102468

ENSMUSG00000034997

UniProt

P28223

P35363

RefSeq (mRNA)

NM_001165947
NM_000621
NM_001378924

NM_172812

RefSeq (protein)

NP_000612
NP_001159419
NP_001365853

NP_766400

Location (UCSC)Chr 13: 46.83 – 46.9 Mbn/a
PubMed search[2][3]
Wikidata
View/Edit HumanView/Edit Mouse

The 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor (GPCR).[4] The 5-HT2A receptor is a cell surface receptor,[5] but has several intracellular locations.[6]

Like all 5-HT2 receptors, the 5-HT2A receptor is Gq/G11-protein coupled. This is the main excitatory receptor subtype among the GPCRs for serotonin, although 5-HT2A may also have an inhibitory effect[7] on certain areas such as the visual cortex and the orbitofrontal cortex.[8] This receptor was first noted for its importance as a target of serotonergic psychedelic drugs such as LSD and psilocybin mushrooms. Later it came back to prominence because it was also found to be mediating, at least partly, the action of many antipsychotic drugs, especially atypical antipsychotics.

Downregulation of post-synaptic 5-HT2A receptor is an adaptive process provoked by chronic administration of selective serotonin reuptake inhibitors (SSRIs) and atypical antipsychotics. Suicidal and otherwise depressed patients have had more 5-HT2A receptors than normal patients. These findings suggest that post-synaptic 5-HT2A overdensity is involved in the pathogenesis of depression.[9]

Paradoxical down-regulation of 5-HT2A receptors can be observed with several 5-HT2A antagonists.[10] Thus, instead of tolerance, reverse-tolerance would be expected from 5-HT2A antagonists. However, there is at least one antagonist at this site which has been shown to up-regulate 5-HT2A receptors.[10][11] Additionally, a couple of other antagonists may have no effect on 5-HT2A receptor number.[12] Nevertheless, upregulation is the exception rather than the rule. Neither tolerance nor rebound is observed in humans with regard to the slow-wave sleep (SWS) promoting effects of 5-HT2A antagonists.[13]

Signaling cascade

The 5-HT2A receptor is known primarily to couple to the Gαq signal transduction pathway. Upon receptor stimulation with agonist, Gαq and β-γ subunits dissociate to initiate downstream effector pathways. Gαq stimulates phospholipase C (PLC) activity, which subsequently promotes the release of diacylglycerol (DAG) and inositol triphosphate (IP3), which in turn stimulate protein kinase C (PKC) activity and Ca2+ release.[14]

History

5-HT receptors were split into two classes by John Gaddum and Picarelli when it was discovered that some of the serotonin-induced changes in the gut could be blocked by morphine, while the remainder of the response was inhibited by dibenzyline, leading to the naming of M and D receptors, respectively. 5-HT2A is thought to correspond to what was originally described as D subtype of 5-HT receptors by Gaddum and Picarelli.[15] In the era before molecular cloning, when radioligand binding and displacement was the only major tool, spiperone and LSD were shown to label two different 5-HT receptors, and neither of them displaced morphine, leading to naming of the 5-HT1, 5-HT2 and 5-HT3 receptors, corresponding to high affinity sites from LSD, spiperone and morphine, respectively.[16] Later it was shown that the 5-HT2 was very close to 5-HT1C and thus were grouped together, renaming the 5-HT2 into 5-HT2A. Thus, the 5-HT2 receptor family is composed of three separate molecular entities: the 5-HT2A (formerly known as 5-HT2 or D), the 5-HT2B (formerly known as 5-HT2F) and the 5-HT2C (formerly known as 5-HT1C) receptors.[17]

Distribution

5-HT2A is expressed widely throughout the central nervous system (CNS).[18] It is expressed near most of the serotonergic terminal rich areas, including neocortex (mainly prefrontal, parietal, and somatosensory cortex) and the olfactory tubercle [citation needed]. Especially high concentrations of this receptor on the apical dendrites of pyramidal cells in layer V of the cortex may modulate cognitive processes, working memory, and attention[19][20][21] by enhancing glutamate release followed by a complex range of interactions with the 5-HT1A,[22] GABAA,[23] adenosine A1,[24] AMPA,[25] mGluR2/3,[26] mGlu5,[27] and OX2 receptors.[28][29] In the rat cerebellum, the protein has also been found in the Golgi cells of the granular layer,[30] and in the Purkinje cells.[31][32]

In the periphery, it is highly expressed in platelets and many cell types of the cardiovascular system, in fibroblasts, and in neurons of the peripheral nervous system. Additionally, 5-HT2A mRNA expression has been observed in human monocytes.[33] Whole-body distribution of the 5-HT2A/2C receptor agonist, [11C]Cimbi-36 show uptake in several internal organs and brown adipose tissue (BAT), but it is not clear if this represents specific 5-HT2A receptor binding.[34]

Effects

Physiological processes mediated by the receptor include:

Ligands

Agonists

Further information: List of miscellaneous 5HT2A agonists

Activation of the 5-HT2A receptor is necessary for the effects of the "classic" psychedelics like LSD, psilocin and mescaline, which act as full or partial agonists at this receptor, and represent the three main classes of 5-HT2A agonists, the ergolines, tryptamines and phenethylamines, respectively. A very large family of derivatives from these three classes has been developed, and their structure-activity relationships have been extensively researched.[48][49] Agonists acting at 5-HT2A receptors located on the apical dendrites of pyramidal cells within regions of the prefrontal cortex are believed to mediate hallucinogenic activity. Some findings reveal that psychoactive effects of classic psychedelics are mediated by the receptor heterodimer 5-HT2A–mGlu2 and not by monomeric 5-HT2A receptors.[50][51][35] However, newer research suggests that 5HT2A and mGlu2 receptors do not physically associate with each other, so the former findings have questionable relevance.[52] Agonists enhance dopamine in PFC,[21] enhance memory and play an active role in attention and learning.[53][54]

Full agonists

  • 25I-NBOH and its 2-methoxy-analog 25I-NBOMe[55]
  • BMB-202 – highly selective[56]
  • 18F FECIMBI-36 – radiolabelled agonist ligand for mapping 5-HT2A / 5-HT2C receptor distribution[57]
  • TCB-2[58]
  • Mexamine (5-methoxytryptamine) – full agonist to several serotonin receptors.
  • O-4310 – 5-HT2A selective, claimed to have 100× selectivity over 5-HT2C and be inactive at 5-HT2B
  • PHA-57378 – dual 5-HT2A / 5-HT2C agonist, anxiolytic effects in animal studies.[59]
  • 25B-NBOMe – also known as Cimbi-36; used as a PET imaging tool for visualizing the 5-HT2A receptor[60]

Partial agonists

Selective agonists

Peripherally selective agonists

One effect of 5-HT2A receptor activation is a reduction in intraocular pressure, and so 5-HT2A agonists can be useful for the treatment of glaucoma. This has led to the development of compounds such as AL-34662 that are hoped to reduce pressure inside the eyes but without crossing the blood–brain barrier and producing hallucinogenic side effects.[91] Animal studies with this compound showed it to be free of hallucinogenic effects at doses up to 30 mg/kg, although several of its more lipophilic analogues did produce the head-twitch response known to be characteristic of hallucinogenic effects in rodents.[92]

Antagonists

Peripherally selective antagonists

Antagonists and cardiovascular disease

Increased 5-HT2A expression is observed in patients with coronary thrombosis, and the receptor has been associated with processes that influence atherosclerosis.[104] As the receptor is present in coronary arteries[105] and capable of mediating vasoconstriction, 5-HT2A has also been linked to coronary artery spasms.[106] 5-HT antagonism, therefore, has potential in the prevention of cardiovascular disease, however, no studies have been published so far.[104]

Inverse agonists

Functional selectivity

5-HT2A-receptor ligands may differentially activate the transductional pathways (see above). Studies evaluated the activation of two effectors, PLC and PLA2, by means of their second messengers. Compounds displaying more pronounced functional selectivity are 2,5-DMA and 2C-N. The former induces IP accumulation without activating the PLA2 mediated response, while the latter elicits AA release without activating the PLC mediated response.[115]

Recent research has suggested potential signaling differences within the somatosensory cortex between 5-HT2A agonists that produce headshakes in the mouse and those that do not, such as lisuride, as these agents are also non-hallucinogenic in humans despite being active 5-HT2A agonists.[116][117] One known example of differences in signal transduction is between the two 5-HT2A agonists serotonin and DOI that involves differential recruitment of intracellular proteins called β-arrestins, more specifically arrestin beta 2.[118][119] Cyclopropylmethanamine derivatives such as (−)-19 have also been shown to act as 5-HT2A/2C agonists with functional selectivity for Gq-mediated signaling compared with β-arrestin recruitment.[120]

Genetics

Chromosome 13.

The 5-HT2A receptors is coded by the HTR2A gene. In humans the gene is located on chromosome 13. The gene has previously been called just HTR2 until the description of two related genes HTR2B and HTR2C. Several interesting polymorphisms have been identified for HTR2A: A-1438G (rs6311), C102T (rs6313) and His452Tyr (rs6314). Many more polymorphisms exist for the gene. A 2006 paper listed 255.[121][64]

Probable role in fibromyalgia as the T102C polymorphisms of the gene 5HT2A were common in fibromyalgia patients.[122]

Human HTR2A gene is thought to consist of 3 introns and 4 exons and to overlap with human gene HTR2A-AS1 which consists of 18 exons.[123] There are over 200 organisms that have orthologs with the human HTR2A. Currently, the best documented orthologs for HTR2A gene are the mouse,[124] and zebrafish.[125] There are 8 paralogs for the HTR2A gene. The HTR2A gene is known to interact and activate G-protein genes such as GNA14, GNAI1, GNAI3, GNAQ, and GNAZ.[126] These interactions are critical for cell signaling[127][128] and homeostasis [129] in many organisms.[130]

In human brain tissue, regulation of HTR2A varies depending on the region:[123] frontal cortex, amygdala, thalamus, brain stem and cerebellum. In a paper from 2016, they found that HTR2A undergoes a variety of different splicing events, including utilization of alternative splice acceptor sites, exon skipping, rare exon usage, and intron retention.[123]

Mechanisms of regulation

There are a few mechanisms of regulation for HTR2A gene such regulated by DNA methylation at particular transcript binding sites.[131][132] Another mechanism for the correct regulation of gene expression is achieved through alternative splicing. This is a co-transcriptional process, which allows the generation of multiple forms of mRNA transcript from a single coding unit and is emerging as an important control point for gene expression. In this process, exons or introns can be either included or excluded from precursor-mRNA resulting in multiple mature mRNA variants.[133] These mRNA variants result in different isoforms which may have antagonistic functions or differential expression patterns, yielding plasticity and adaptability to the cells.[134] One study found that the common genetic variant rs6311 regulates expression of HTR2A transcripts containing the extended 5' UTR.[123]

Associations with psychiatric disorders

Several studies have seen links between the -1438G/A polymorphism and mood disorders, such as major depressive disorder.[135] and a strong link with an odds ratio of 1.3 has been found between the T102C polymorphism and schizophrenia.[136] This polymorphism has also been studied in relation to suicide attempts, with a study finding excess of the G/G and G/A genotypes among the suicide attempters.[137] A number of other studies were devoted to finding an association of the gene with schizophrenia, with diverging results.[138]

These individual studies may, however, not give a full picture: A review from 2007 looking at the effect of different SNPs reported in separate studies stated that "genetic association studies [of HTR2A gene variants with psychiatric disorders] report conflicting and generally negative results" with no involvement, small or a not replicated role for the genetic variant of the gene.[139]

Polymorphisms in the promoter gene coding Early growth response 3 (EGR3) are associated with schizophrenia. Studies have demonstrated a relationship between EGR3 and HTR2A, and schizophrenia-like behaviors in transgenic animals.[140][141] Exactly how these results translate over to further biopsychological understanding of schizophrenia is still widely debated.[142][143] There is some evidence that dysfunction of HTR2A can impact pharmacological interventions.[144]

Several studies have assessed a relationship between 5-hydroxytryptamine (serotonin) 2A receptor (5-HTR2A) gene polymorphisms with an increased risk of suicidal behavior. One study revealed that T102C polymorphism is associated with suicidal behavior [145] but other studies failed to replicate these findings and found no association between polymorphism and suicidal behavior.[146]

Treatment response

Genetics seems also to be associated to some extent with the amount of adverse events in treatment of major depression disorder.[147]

Associations with substance abuse

Polymorphisms in the 5-HT2A receptor coding gene HTR2A (rs6313 and s6311) have been shown to have conflicting associations with alcohol misuse. For example, A polymorphism in the 5-HT2A receptor coding gene HTR2A (rs6313) was reported to predict lower positive alcohol expectancy, higher refusal self-efficacy, and lower alcohol misuse in a sample of 120 young adults. However, this polymorphism did not moderate the linkages between impulsivity, cognition, and alcohol misuse.[148] There are conflicting results as other studies have found associations between T102C polymorphisms alcohol misuse.[149][150]

Drug impact on gene expression

There is some evidence that methylation patterns may contribute to relapse behaviors in people who use stimulants.[151] In mice, psychotropic drugs such as DOI, LSD, DOM, and DOB which produced differing transcriptional patterns among several different brain regions.[141]

Methods to analyse the receptor

The receptor can be analysed by neuroimaging, radioligand, genetic analysis, measurements of ion flows, and in other ways.

Neuroimaging

The 5-HT2A receptors may be imaged with PET-scanners using the fluorine-18-altanserin,[152] MDL 100,907[153] or [11C]Cimbi-36[60][154] radioligands that binds to the neuroreceptor, e.g., one study reported a reduced binding of altanserin particularly in the hippocampus in patients with major depressive disorder.[155]

Altanserin uptake decreases with age reflecting a loss of specific 5-HT2A receptors with age.[156][157][158]

Other

Western blot with an affinity-purified antibody and examination of 5-HT2A receptor protein samples by electrophoresis has been described. Immunohistochemical staining of 5-HT2A receptors is also possible.[5]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000102468 – Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ Cook EH, Fletcher KE, Wainwright M, Marks N, Yan SY, Leventhal BL (August 1994). "Primary structure of the human platelet serotonin 5-HT2A receptor: identify with frontal cortex serotonin 5-HT2A receptor". Journal of Neurochemistry. 63 (2): 465–469. doi:10.1046/j.1471-4159.1994.63020465.x. PMID 8035173. S2CID 40207336.
  5. ^ a b c Kling A (2013). 5-HT2A: a serotonin receptor with a possible role in joint diseases (PDF). Umeå: Umeå Universitet. ISBN 978-91-7459-549-9.
  6. ^ Raote I (2007). "Serotonin 2A (5-HT2A) Receptor Function: Ligand-Dependent Mechanisms and Pathways". Ishier. Frontiers in Neuroscience. Press/Taylor & Francis. ISBN 9780849339776. PMID 21204452.
  7. ^ Martin P, Waters N, Schmidt CJ, Carlsson A, Carlsson ML (1998). "Rodent data and general hypothesis: antipsychotic action exerted through 5-HT2A receptor antagonism is dependent on increased serotonergic tone". Journal of Neural Transmission. 105 (4–5): 365–396. doi:10.1007/s007020050064. PMID 9720968. S2CID 20944107.
  8. ^ De Almeida RM, Rosa MM, Santos DM, Saft DM, Benini Q, Miczek KA (May 2006). "5-HT(1B) receptors, ventral orbitofrontal cortex, and aggressive behavior in mice". Psychopharmacology. 185 (4): 441–450. doi:10.1007/s00213-006-0333-3. PMID 16550387. S2CID 33274637.
  9. ^ Eison AS, Mullins UL (1996). "Regulation of central 5-HT2A receptors: a review of in vivo studies". Behavioural Brain Research. 73 (1–2): 177–181. doi:10.1016/0166-4328(96)00092-7. PMID 8788498. S2CID 4048975.
  10. ^ a b Yadav PN, Kroeze WK, Farrell MS, Roth BL (October 2011). "Antagonist functional selectivity: 5-HT2A serotonin receptor antagonists differentially regulate 5-HT2A receptor protein level in vivo". The Journal of Pharmacology and Experimental Therapeutics. 339 (1): 99–105. doi:10.1124/jpet.111.183780. PMC 3186284. PMID 21737536.
  11. ^ Rinaldi-Carmona M, Congy C, Simiand J, Oury-Donat F, Soubrie P, Breliere JC, et al. (January 1993). "Repeated administration of SR 46349B, a selective 5-hydroxytryptamine2 antagonist, up-regulates 5-hydroxytryptamine2 receptors in mouse brain". Molecular Pharmacology. 43 (1): 84–89. PMID 8423772.
  12. ^ Gray JA, Roth BL (November 2001). "Paradoxical trafficking and regulation of 5-HT(2A) receptors by agonists and antagonists". Brain Research Bulletin. 56 (5): 441–451. doi:10.1016/s0361-9230(01)00623-2. PMID 11750789. S2CID 271925.
  13. ^ Vanover KE, Davis RE (28 July 2010). "Role of 5-HT2A receptor antagonists in the treatment of insomnia". Nature and Science of Sleep. 2: 139–150. doi:10.2147/nss.s6849. PMC 3630942. PMID 23616706.
  14. ^ Urban JD, Clarke WP, von Zastrow M, Nichols DE, Kobilka B, Weinstein H, et al. (January 2007). "Functional selectivity and classical concepts of quantitative pharmacology". The Journal of Pharmacology and Experimental Therapeutics. 320 (1): 1–13. doi:10.1124/jpet.106.104463. PMID 16803859. S2CID 447937.
  15. ^ Sanders-Bush E, Mayer SE (2006). "Chapter 11: 5-Hydroxytryptamine (Serotonin): Receptor Agonists and Antagonists". In Brunton LL, Lazo JS, Parker K (eds.). Goodman & Gilman's the Pharmacological Basis of Therapeutics (11th ed.). New York: McGraw-Hill. ISBN 0-07-142280-3.
  16. ^ Siegel GJ, Albers RW (2005). Basic neurochemistry: molecular, cellular, and medical aspects. Vol. 1 (7th ed.). Academic Press. p. 241. ISBN 0-12-088397-X.
  17. ^ Hoyer D, Hannon JP, Martin GR (April 2002). "Molecular, pharmacological and functional diversity of 5-HT receptors". Pharmacology, Biochemistry, and Behavior. 71 (4): 533–554. doi:10.1016/S0091-3057(01)00746-8. PMID 11888546. S2CID 25543069.
  18. ^ Beliveau V, Ganz M, Feng L, Ozenne B, Højgaard L, Fisher PM, et al. (January 2017). "A High-Resolution In Vivo Atlas of the Human Brain's Serotonin System". The Journal of Neuroscience. 37 (1): 120–128. doi:10.1523/JNEUROSCI.2830-16.2016. PMC 5214625. PMID 28053035.
  19. ^ Aghajanian GK, Marek GJ (April 1999). "Serotonin, via 5-HT2A receptors, increases EPSCs in layer V pyramidal cells of prefrontal cortex by an asynchronous mode of glutamate release". Brain Research. 825 (1–2): 161–171. doi:10.1016/S0006-8993(99)01224-X. PMID 10216183. S2CID 20081913.
  20. ^ Marek GJ, Wright RA, Gewirtz JC, Schoepp DD (2001). "A major role for thalamocortical afferents in serotonergic hallucinogen receptor function in the rat neocortex". Neuroscience. 105 (2): 379–392. doi:10.1016/S0306-4522(01)00199-3. PMID 11672605. S2CID 19764312.
  21. ^ a b c Bortolozzi A, Díaz-Mataix L, Scorza MC, Celada P, Artigas F (December 2005). "The activation of 5-HT receptors in prefrontal cortex enhances dopaminergic activity". Journal of Neurochemistry. 95 (6): 1597–1607. doi:10.1111/j.1471-4159.2005.03485.x. hdl:10261/33026. PMID 16277612. S2CID 18350703.
  22. ^ Amargós-Bosch M, Bortolozzi A, Puig MV, Serrats J, Adell A, Celada P, et al. (March 2004). "Co-expression and in vivo interaction of serotonin1A and serotonin2A receptors in pyramidal neurons of prefrontal cortex". Cerebral Cortex. 14 (3): 281–299. doi:10.1093/cercor/bhg128. hdl:10261/34683. PMID 14754868.
  23. ^ Feng J, Cai X, Zhao J, Yan Z (September 2001). "Serotonin receptors modulate GABA(A) receptor channels through activation of anchored protein kinase C in prefrontal cortical neurons". The Journal of Neuroscience. 21 (17): 6502–6511. doi:10.1523/JNEUROSCI.21-17-06502.2001. PMC 6763081. PMID 11517239.
  24. ^ Marek GJ (June 2009). "Activation of adenosine(1) (A(1)) receptors suppresses head shakes induced by a serotonergic hallucinogen in rats". Neuropharmacology. 56 (8): 1082–1087. doi:10.1016/j.neuropharm.2009.03.005. PMC 2706691. PMID 19324062.
  25. ^ Zhang C, Marek GJ (January 2008). "AMPA receptor involvement in 5-hydroxytryptamine2A receptor-mediated pre-frontal cortical excitatory synaptic currents and DOI-induced head shakes". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 32 (1): 62–71. doi:10.1016/j.pnpbp.2007.07.009. PMID 17728034. S2CID 44889209.
  26. ^ Gewirtz JC, Marek GJ (November 2000). "Behavioral evidence for interactions between a hallucinogenic drug and group II metabotropic glutamate receptors". Neuropsychopharmacology. 23 (5): 569–576. doi:10.1016/S0893-133X(00)00136-6. PMID 11027922.
  27. ^ Marek GJ, Zhang C (September 2008). "Activation of metabotropic glutamate 5 (mGlu5) receptors induces spontaneous excitatory synaptic currents in layer V pyramidal cells of the rat prefrontal cortex". Neuroscience Letters. 442 (3): 239–243. doi:10.1016/j.neulet.2008.06.083. PMC 2677702. PMID 18621097.
  28. ^ Lambe EK, Liu RJ, Aghajanian GK (November 2007). "Schizophrenia, hypocretin (orexin), and the thalamocortical activating system". Schizophrenia Bulletin. 33 (6): 1284–1290. doi:10.1093/schbul/sbm088. PMC 2779889. PMID 17656637.
  29. ^ Liu RJ, Aghajanian GK (January 2008). "Stress blunts serotonin- and hypocretin-evoked EPSCs in prefrontal cortex: role of corticosterone-mediated apical dendritic atrophy". Proceedings of the National Academy of Sciences of the United States of America. 105 (1): 359–364. Bibcode:2008PNAS..105..359L. doi:10.1073/pnas.0706679105. PMC 2224217. PMID 18172209.
  30. ^ Geurts FJ, De Schutter E, Timmermans JP (June 2002). "Localization of 5-HT2A, 5-HT3, 5-HT5A and 5-HT7 receptor-like immunoreactivity in the rat cerebellum". Journal of Chemical Neuroanatomy. 24 (1): 65–74. doi:10.1016/S0891-0618(02)00020-0. PMID 12084412. S2CID 16510169.
  31. ^ Maeshima T, Shutoh F, Hamada S, Senzaki K, Hamaguchi-Hamada K, Ito R, et al. (August 1998). "Serotonin2A receptor-like immunoreactivity in rat cerebellar Purkinje cells". Neuroscience Letters. 252 (1): 72–74. doi:10.1016/S0304-3940(98)00546-1. PMID 9756362. S2CID 28549709.
  32. ^ Maeshima T, Shiga T, Ito R, Okado N (December 2004). "Expression of serotonin2A receptors in Purkinje cells of the developing rat cerebellum". Neuroscience Research. 50 (4): 411–417. doi:10.1016/j.neures.2004.08.010. PMID 15567478. S2CID 5772490.
  33. ^ Dürk T, Panther E, Müller T, Sorichter S, Ferrari D, Pizzirani C, et al. (May 2005). "5-Hydroxytryptamine modulates cytokine and chemokine production in LPS-primed human monocytes via stimulation of different 5-HTR subtypes". International Immunology. 17 (5): 599–606. doi:10.1093/intimm/dxh242. PMID 15802305.
  34. ^ Johansen A, Holm S, Dall B, Keller S, Kristensen JL, Knudsen GM, et al. (July 2019). "Human biodistribution and radiation dosimetry of the 5-HT2A receptor agonist Cimbi-36 labeled with carbon-11 in two positions". EJNMMI Research. 9 (1): 71. doi:10.1186/s13550-019-0527-4. PMC 6669221. PMID 31367837.
  35. ^ a b Moreno JL, Holloway T, Albizu L, Sealfon SC, González-Maeso J (April 2011). "Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists". Neuroscience Letters. 493 (3): 76–79. doi:10.1016/j.neulet.2011.01.046. PMC 3064746. PMID 21276828.
  36. ^ a b Jalal B (November 2018). "The neuropharmacology of sleep paralysis hallucinations: serotonin 2A activation and a novel therapeutic drug". Psychopharmacology. 235 (11): 3083–3091. doi:10.1007/s00213-018-5042-1. PMC 6208952. PMID 30288594.
  37. ^ Yu B, Becnel J, Zerfaoui M, Rohatgi R, Boulares AH, Nichols CD (November 2008). "Serotonin 5-hydroxytryptamine(2A) receptor activation suppresses tumor necrosis factor-alpha-induced inflammation with extraordinary potency". The Journal of Pharmacology and Experimental Therapeutics. 327 (2): 316–323. doi:10.1124/jpet.108.143461. PMID 18708586. S2CID 25374241.
  38. ^ Nau F, Yu B, Martin D, Nichols CD (2013). "Serotonin 5-HT2A receptor activation blocks TNF-α mediated inflammation in vivo". PLOS ONE. 8 (10): e75426. Bibcode:2013PLoSO...875426N. doi:10.1371/journal.pone.0075426. PMC 3788795. PMID 24098382.
  39. ^ Van de Kar LD, Javed A, Zhang Y, Serres F, Raap DK, Gray TS (May 2001). "5-HT2A receptors stimulate ACTH, corticosterone, oxytocin, renin, and prolactin release and activate hypothalamic CRF and oxytocin-expressing cells". The Journal of Neuroscience. 21 (10): 3572–3579. doi:10.1523/JNEUROSCI.21-10-03572.2001. PMC 6762485. PMID 11331386.
  40. ^ Zhang Y, Damjanoska KJ, Carrasco GA, Dudas B, D'Souza DN, Tetzlaff J, et al. (November 2002). "Evidence that 5-HT2A receptors in the hypothalamic paraventricular nucleus mediate neuroendocrine responses to (−)DOI". The Journal of Neuroscience. 22 (21): 9635–9642. doi:10.1523/JNEUROSCI.22-21-09635.2002. PMC 6758011. PMID 12417689.
  41. ^ Harvey JA (2003). "Role of the serotonin 5-HT(2A) receptor in learning". Learning & Memory. 10 (5): 355–362. doi:10.1101/lm.60803. PMC 218001. PMID 14557608.
  42. ^ Williams GV, Rao SG, Goldman-Rakic PS, Foresta M, Ropolo M, Degan P, et al. (March 2010). "Defective repair of 5-hydroxy-2'-deoxycytidine in Cockayne syndrome cells and its complementation by Escherichia coli formamidopyrimidine DNA glycosylase and endonuclease III". Free Radical Biology & Medicine. 48 (5): 681–690. doi:10.1016/j.freeradbiomed.2009.12.007. PMC 6758292. PMID 11923449.
  43. ^ Passier A, van Puijenbroek E (November 2005). "Mirtazapine-induced arthralgia". British Journal of Clinical Pharmacology. 60 (5): 570–572. doi:10.1111/j.1365-2125.2005.02481.x. PMC 1884949. PMID 16236049.
  44. ^ Adwan MH (August 2016). "An update on drug-induced arthritis". Rheumatology International. 36 (8): 1089–1097. doi:10.1007/s00296-016-3462-y. PMID 27000044. S2CID 25401280.
  45. ^ Herth MM, Knudsen GM (June 2015). "Current radiosynthesis strategies for 5-HT2A receptor PET tracers". Journal of Labelled Compounds & Radiopharmaceuticals. 58 (7): 265–273. doi:10.1002/jlcr.3288. PMID 25997728.
  46. ^ Beer R (13 June 2023). "Anblick von toten Fliegen lässt Fliegen altern". science.ORF.at (in German). Retrieved 14 June 2023.
  47. ^ Gendron CM, Chakraborty TS, Duran C, Dono T, Pletcher SD (June 2023). "Ring neurons in the Drosophila central complex act as a rheostat for sensory modulation of aging". PLOS Biology. 21 (6): e3002149. doi:10.1371/journal.pbio.3002149. PMC 10263353. PMID 37310911.
  48. ^ Nichols DE (February 2004). "Hallucinogens". Pharmacology & Therapeutics. 101 (2): 131–181. doi:10.1016/j.pharmthera.2003.11.002. PMID 14761703.
  49. ^ Blaazer AR, Smid P, Kruse CG (September 2008). "Structure-activity relationships of phenylalkylamines as agonist ligands for 5-HT(2A) receptors". ChemMedChem. 3 (9): 1299–1309. doi:10.1002/cmdc.200800133. PMID 18666267. S2CID 7537908.
  50. ^ Moreno JL, Muguruza C, Umali A, Mortillo S, Holloway T, Pilar-Cuéllar F, et al. (December 2012). "Identification of three residues essential for 5-hydroxytryptamine 2A-metabotropic glutamate 2 (5-HT2A·mGlu2) receptor heteromerization and its psychoactive behavioral function". The Journal of Biological Chemistry. 287 (53): 44301–44319. doi:10.1074/jbc.M112.413161. PMC 3531745. PMID 23129762.
  51. ^ González-Maeso J, Ang RL, Yuen T, Chan P, Weisstaub NV, López-Giménez JF, et al. (March 2008). "Identification of a serotonin/glutamate receptor complex implicated in psychosis". Nature. 452 (7183): 93–97. Bibcode:2008Natur.452...93G. doi:10.1038/nature06612. PMC 2743172. PMID 18297054.
  52. ^ Taddeucci A, Olivero G, Roggeri A, Milanese C, Giorgio FP, Grilli M, et al. (September 2022). "Presynaptic 5-HT2A-mGlu2/3 Receptor-Receptor Crosstalk in the Prefrontal Cortex: Metamodulation of Glutamate Exocytosis". Cells. 11 (19): 3035. doi:10.3390/cells11193035. PMC 9562019. PMID 36230998.
  53. ^ Wingen M, Kuypers KP, Ramaekers JG (February 2007). "The role of 5-HT1a and 5-HT2A receptors in attention and motor control: a mechanistic study in healthy volunteers". Psychopharmacology. 190 (3): 391–400. doi:10.1007/s00213-006-0614-x. PMID 17124621. S2CID 25125461.
  54. ^ Wingen M, Kuypers KP, Ramaekers JG (July 2007). "Selective verbal and spatial memory impairment after 5-HT1A and 5-HT2A receptor blockade in healthy volunteers pre-treated with an SSRI". Journal of Psychopharmacology. 21 (5): 477–485. doi:10.1177/0269881106072506. PMID 17092965. S2CID 19575488.
  55. ^ Braden MR, Parrish JC, Naylor JC, Nichols DE (December 2006). "Molecular interaction of serotonin 5-HT2A receptor residues Phe339(6.51) and Phe340(6.52) with superpotent N-benzyl phenethylamine agonists". Molecular Pharmacology. 70 (6): 1956–1964. doi:10.1124/mol.106.028720. PMID 17000863. S2CID 15840304.
  56. ^ a b Vasilkevich A, Halberstadt AL, Duan J, Merritt CR, Cunningham KA, McCorvy J, et al. (October 2024). Novel 5-HT2A selective agonists with well-characterized PK profile and short duration of action (PDF). Society for Neuroscience 2024 Annual Meeting (Chicago), October 5-9.
  57. ^ Prabhakaran J, Solingapuram Sai KK, Zanderigo F, Rubin-Falcone H, Jorgensen MJ, Kaplan JR, et al. (January 2017). "In vivo evaluation of [18F]FECIMBI-36, an agonist 5-HT2A/2C receptor PET radioligand in nonhuman primate". Bioorganic & Medicinal Chemistry Letters. 27 (1): 21–23. doi:10.1016/j.bmcl.2016.11.043. PMC 5348621. PMID 27889455.
  58. ^ McLean TH, Parrish JC, Braden MR, Marona-Lewicka D, Gallardo-Godoy A, Nichols DE (September 2006). "1-Aminomethylbenzocycloalkanes: conformationally restricted hallucinogenic phenethylamine analogues as functionally selective 5-HT2A receptor agonists". Journal of Medicinal Chemistry. 49 (19): 5794–5803. doi:10.1021/jm060656o. PMID 16970404.
  59. ^ Ennis MD, Hoffman RL, Ghazal NB, Olson RM, Knauer CS, Chio CL, et al. (July 2003). "2,3,4,5-tetrahydro- and 2,3,4,5,11,11a-hexahydro-1H-[1,4]diazepino[1,7-a]indoles: new templates for 5-HT(2C) agonists". Bioorganic & Medicinal Chemistry Letters. 13 (14): 2369–2372. doi:10.1016/S0960-894X(03)00403-7. PMID 12824036.
  60. ^ a b Ettrup A, da Cunha-Bang S, McMahon B, Lehel S, Dyssegaard A, Skibsted AW, et al. (July 2014). "Serotonin 2A receptor agonist binding in the human brain with [¹¹C]Cimbi-36". Journal of Cerebral Blood Flow and Metabolism. 34 (7): 1188–1196. doi:10.1038/jcbfm.2014.68. PMC 4083382. PMID 24780897.
  61. ^ "Design and Synthesis of Selective Serotonin Receptor Agonists for Positron Emission Tomography Imaging of the Brain (Revised, Duplex print).pdf". Google Docs.
  62. ^ Dong C, Ly C, Dunlap LE, Vargas MV, Sun J, Hwang IW, et al. (May 2021). "Psychedelic-inspired drug discovery using an engineered biosensor". Cell. 184 (10): 2779–2792.e18. doi:10.1016/j.cell.2021.03.043. PMC 8122087. PMID 33915107.
  63. ^ Vasilkevich A, Duan J, Lovera A, McCorvy J, Pedersen JT (October 2024). Novel 5-HT2A/2C mixed and partial agonist and its efficacy in preclinical pain models (PDF). Society for Neuroscience 2024 Annual Meeting, Chicago, October 5-9.
  64. ^ a b Chambers JJ, Kurrasch-Orbaugh DM, Parker MA, Nichols DE (March 2001). "Enantiospecific synthesis and pharmacological evaluation of a series of super-potent, conformationally restricted 5-HT(2A/2C) receptor agonists". Journal of Medicinal Chemistry. 44 (6): 1003–1010. doi:10.1021/jm000491y. PMID 11300881.
  65. ^ Canal CE, Morgan D (July 2012). "Head-twitch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine: a comprehensive history, a re-evaluation of mechanisms, and its utility as a model". Drug Testing and Analysis. 4 (7–8): 556–576. doi:10.1002/dta.1333. PMC 3722587. PMID 22517680.
  66. ^ Gatch MB, Kozlenkov A, Huang RQ, Yang W, Nguyen JD, González-Maeso J, et al. (November 2013). "The HIV antiretroviral drug efavirenz has LSD-like properties". Neuropsychopharmacology. 38 (12): 2373–2384. doi:10.1038/npp.2013.135. PMC 3799056. PMID 23702798.
  67. ^ Juncosa JI, Hansen M, Bonner LA, Cueva JP, Maglathlin R, McCorvy JD, et al. (January 2013). "Extensive rigid analogue design maps the binding conformation of potent N-benzylphenethylamine 5-HT2A serotonin receptor agonist ligands". ACS Chemical Neuroscience. 4 (1): 96–109. doi:10.1021/cn3000668. PMC 3547484. PMID 23336049.
  68. ^ Egan CT, Herrick-Davis K, Miller K, Glennon RA, Teitler M (April 1998). "Agonist activity of LSD and lisuride at cloned 5HT2A and 5HT2C receptors". Psychopharmacology. 136 (4): 409–414. doi:10.1007/s002130050585. PMID 9600588. S2CID 3021798.
  69. ^ Hofmann C, Penner U, Dorow R, Pertz HH, Jähnichen S, Horowski R, et al. (2006). "Lisuride, a dopamine receptor agonist with 5-HT2B receptor antagonist properties: absence of cardiac valvulopathy adverse drug reaction reports supports the concept of a crucial role for 5-HT2B receptor agonism in cardiac valvular fibrosis". Clinical Neuropharmacology. 29 (2): 80–86. doi:10.1097/00002826-200603000-00005. PMID 16614540. S2CID 33849447.
  70. ^ Janowsky A, Eshleman AJ, Johnson RA, Wolfrum KM, Hinrichs DJ, Yang J, et al. (July 2014). "Mefloquine and psychotomimetics share neurotransmitter receptor and transporter interactions in vitro". Psychopharmacology. 231 (14): 2771–2783. doi:10.1007/s00213-014-3446-0. PMC 4097020. PMID 24488404.
  71. ^ de la Fuente Revenga M, Shah UH, Nassehi N, Jaster AM, Hemanth P, Sierra S, et al. (March 2021). "Psychedelic-like Properties of Quipazine and Its Structural Analogues in Mice". ACS Chemical Neuroscience. 12 (5): 831–844. doi:10.1021/acschemneuro.0c00291. PMC 7933111. PMID 33400504.
  72. ^ Åstrand A, Guerrieri D, Vikingsson S, Kronstrand R, Green H (December 2020). "In vitro characterization of new psychoactive substances at the μ-opioid, CB1, 5HT1A, and 5-HT2A receptors-On-target receptor potency and efficacy, and off-target effects". Forensic Science International. 317: 110553. doi:10.1016/j.forsciint.2020.110553. PMID 33160102.
  73. ^ Ennis MD, Hoffman RL, Ghazal NB, Olson RM, Knauer CS, Chio CL, et al. (July 2003). "2,3,4,5-tetrahydro- and 2,3,4,5,11,11a-hexahydro-1H-[1,4]diazepino[1,7-a]indoles: new templates for 5-HT(2C) agonists". Bioorganic & Medicinal Chemistry Letters. 13 (14): 2369–2372. doi:10.1016/s0960-894x(03)00403-7. PMID 12824036.
  74. ^ Smith BM, Smith JM, Tsai JH, Schultz JA, Gilson CA, Estrada SA, et al. (March 2005). "Discovery and SAR of new benzazepines as potent and selective 5-HT(2C) receptor agonists for the treatment of obesity". Bioorganic & Medicinal Chemistry Letters. 15 (5): 1467–1470. doi:10.1016/j.bmcl.2004.12.080. PMID 15713408.
  75. ^ WO WO2007149728, Mohapatra S, Hellberg MR, Feng Z, "Aryl and heteroaryl tetrahydrobenzazepine derivatives and their use for treating glaucoma", assigned to Alcon Manufacturing, Ltd. 
  76. ^ Smith BM, Smith JM, Tsai JH, Schultz JA, Gilson CA, Estrada SA, et al. (January 2008). "Discovery and structure-activity relationship of (1R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3-benzazepine (Lorcaserin), a selective serotonin 5-HT2C receptor agonist for the treatment of obesity". Journal of Medicinal Chemistry. 51 (2): 305–313. doi:10.1021/jm0709034. PMID 18095642.
  77. ^ Jensen AA, Plath N, Pedersen MH, Isberg V, Krall J, Wellendorph P, et al. (February 2013). "Design, synthesis, and pharmacological characterization of N- and O-substituted 5,6,7,8-tetrahydro-4H-isoxazolo[4,5-d]azepin-3-ol analogues: novel 5-HT(2A)/5-HT(2C) receptor agonists with pro-cognitive properties". Journal of Medicinal Chemistry. 56 (3): 1211–1227. doi:10.1021/jm301656h. PMID 23301527.
  78. ^ Cao D, Yu J, Wang H, Luo Z, Liu X, He L, et al. (January 2022). "Structure-based discovery of nonhallucinogenic psychedelic analogs". Science. 375 (6579): 403–411. Bibcode:2022Sci...375..403C. doi:10.1126/science.abl8615. PMID 35084960. S2CID 246360313.
  79. ^ Kaplan AL, Confair DN, Kim K, Barros-Álvarez X, Rodriguiz RM, Yang Y, et al. (October 2022). "Bespoke library docking for 5-HT2A receptor agonists with antidepressant activity". Nature. 610 (7932): 582–591. Bibcode:2022Natur.610..582K. doi:10.1038/s41586-022-05258-z. PMC 9996387. PMID 36171289. S2CID 252598838.
  80. ^ Lyu J, Kapolka N, Gumpper R, Alon A, Wang L, Jain MK, et al. (December 2023). "AlphaFold2 structures template ligand discovery". bioRxiv. doi:10.1101/2023.12.20.572662. PMC 10769324. PMID 38187536.
  81. ^ Orr MJ, Cao AB, Wang CT, Gaisin A, Csakai A, Friswold AP, et al. (April 2022). "Discovery of Highly Potent Serotonin 5-HT2 Receptor Agonists Inspired by Heteroyohimbine Natural Products". ACS Medicinal Chemistry Letters. 13 (4): 648–657. doi:10.1021/acsmedchemlett.1c00694. PMC 9014500. PMID 35450369.
  82. ^ Märcher Rørsted E, Jensen AA, Kristensen JL (November 2021). "25CN-NBOH: A Selective Agonist for in vitro and in vivo Investigations of the Serotonin 2A Receptor". ChemMedChem. 16 (21): 3263–3270. doi:10.1002/cmdc.202100395. PMID 34288515.
  83. ^ a b c Duan W, Cao D, Wang S, Cheng J (January 2024). "Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants". Chem Rev. 124 (1): 124–163. doi:10.1021/acs.chemrev.3c00375. PMID 38033123.
  84. ^ Juncosa JI, Hansen M, Bonner LA, Cueva JP, Maglathlin R, McCorvy JD, et al. (January 2013). "Extensive rigid analogue design maps the binding conformation of potent N-benzylphenethylamine 5-HT2A serotonin receptor agonist ligands". ACS Chem Neurosci. 4 (1): 96–109. doi:10.1021/cn3000668. PMC 3547484. PMID 23336049.
  85. ^ M Ro Rsted E, Jensen AA, Smits G, Frydenvang K, Kristensen JL (May 2024). "Discovery and Structure-Activity Relationships of 2,5-Dimethoxyphenylpiperidines as Selective Serotonin 5-HT2A Receptor Agonists". Journal of Medicinal Chemistry. 67 (9): 7224–7244. doi:10.1021/acs.jmedchem.4c00082. PMC 11089506. PMID 38648420.
  86. ^ Jensen AA, Cecchi CR, Hibicke M, Bach AH, Kaadt E, Marcher-Rorsted E, et al. (22 April 2024). "The selective 5-HT 2A receptor agonist LPH-5 induces persistent and robust antidepressant-like effects in rodents". bioRxiv. doi:10.1101/2024.04.19.590212.
  87. ^ "LPH 48". AdisInsight. 22 May 2024. Retrieved 30 October 2024.
  88. ^ Yuan H, Guo Z, Luo T (February 2017). "Synthesis of (+)-Lysergol and Its Analogues To Assess Serotonin Receptor Activity". Org Lett. 19 (3): 624–627. doi:10.1021/acs.orglett.6b03779. PMID 28106398.
  89. ^ US 7655691, Kumaran G, Morency C, Roth B, Sard HP, Shuster L Xu L, "Indole compounds useful as serotonin selective agents.", published 11 May 2006, assigned to Organix Inc 
  90. ^ Motaghinejad O, Motaghinejad M, Motevalian M, Rahimi-Sharbaf F, Beiranvand T (October 2017). "The effect of maternal forced exercise on offspring pain perception, motor activity and anxiety disorder: the role of 5-HT2 and D2 receptors and CREB gene expression". Journal of Exercise Rehabilitation. 13 (5): 514–525. doi:10.12965/jer.1734992.496. PMC 5667597. PMID 29114525.
  91. ^ Sharif NA, McLaughlin MA, Kelly CR (February 2007). "AL-34662: a potent, selective, and efficacious ocular hypotensive serotonin-2 receptor agonist". Journal of Ocular Pharmacology and Therapeutics. 23 (1): 1–13. doi:10.1089/jop.2006.0093. PMID 17341144.
  92. ^ May JA, Dantanarayana AP, Zinke PW, McLaughlin MA, Sharif NA (January 2006). "1-((S)-2-aminopropyl)-1H-indazol-6-ol: a potent peripherally acting 5-HT2 receptor agonist with ocular hypotensive activity". Journal of Medicinal Chemistry. 49 (1): 318–328. doi:10.1021/jm050663x. PMID 16392816.
  93. ^ Marek GJ, Martin-Ruiz R, Abo A, Artigas F (December 2005). "The selective 5-HT2A receptor antagonist M100907 enhances antidepressant-like behavioral effects of the SSRI fluoxetine". Neuropsychopharmacology. 30 (12): 2205–2215. doi:10.1038/sj.npp.1300762. PMID 15886717.
  94. ^ Ishima T, Futamura T, Ohgi Y, Yoshimi N, Kikuchi T, Hashimoto K (April 2015). "Potentiation of neurite outgrowth by brexpiprazole, a novel serotonin-dopamine activity modulator: a role for serotonin 5-HT1A and 5-HT2A receptors". European Neuropsychopharmacology. 25 (4): 505–511. doi:10.1016/j.euroneuro.2015.01.014. PMID 25687838.
  95. ^ Das S, Barnwal P, Winston AB, Mondal S, Saha I (February 2016). "Brexpiprazole: so far so good". Therapeutic Advances in Psychopharmacology. 6 (1): 39–54. doi:10.1177/2045125315614739. PMC 4749739. PMID 26913177.
  96. ^ a b Pälvimäki EP, Roth BL, Majasuo H, Laakso A, Kuoppamäki M, Syvälahti E, et al. (August 1996). "Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c receptor". Psychopharmacology. 126 (3): 234–240. doi:10.1007/bf02246453. PMID 8876023. S2CID 24889381.
  97. ^ Rang HP (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 187
  98. ^ Shireman BT, Dvorak CA, Rudolph DA, Bonaventure P, Nepomuceno D, Dvorak L, et al. (March 2008). "2-Alkyl-4-aryl-pyrimidine fused heterocycles as selective 5-HT2A antagonists". Bioorganic & Medicinal Chemistry Letters. 18 (6): 2103–2108. doi:10.1016/j.bmcl.2008.01.090. PMID 18282705.
  99. ^ Westkaemper RB, Runyon SP, Bondarev ML, Savage JE, Roth BL, Glennon RA (September 1999). "9-(Aminomethyl)-9,10-dihydroanthracene is a novel and unlikely 5-HT2A receptor antagonist". European Journal of Pharmacology. 380 (1): R5–R7. doi:10.1016/S0014-2999(99)00525-7. PMID 10513561.
  100. ^ Westkaemper RB, Glennon RA (June 2002). "Application of ligand SAR, receptor modeling and receptor mutagenesis to the discovery and development of a new class of 5-HT(2A) ligands". Current Topics in Medicinal Chemistry. 2 (6): 575–598. doi:10.2174/1568026023393741. PMID 12052195. S2CID 23576058.
  101. ^ Peddi S, Roth BL, Glennon RA, Westkaemper RB (December 2003). "Spiro[9,10-dihydroanthracene]-9,3'-pyrrolidine-a structurally unique tetracyclic 5-HT2A receptor antagonist". European Journal of Pharmacology. 482 (1–3): 335–337. doi:10.1016/j.ejphar.2003.09.059. PMID 14660041.
  102. ^ Runyon SP, Mosier PD, Roth BL, Glennon RA, Westkaemper RB (November 2008). "Potential modes of interaction of 9-aminomethyl-9,10-dihydroanthracene (AMDA) derivatives with the 5-HT2A receptor: a ligand structure-affinity relationship, receptor mutagenesis and receptor modeling investigation". Journal of Medicinal Chemistry. 51 (21): 6808–6828. doi:10.1021/jm800771x. PMC 3088499. PMID 18847250.
  103. ^ Wilson KJ, van Niel MB, Cooper L, Bloomfield D, O'Connor D, Fish LR, et al. (May 2007). "2,5-Disubstituted pyridines: the discovery of a novel series of 5-HT2A ligands". Bioorganic & Medicinal Chemistry Letters. 17 (9): 2643–2648. doi:10.1016/j.bmcl.2007.01.098. PMID 17314044.
  104. ^ a b Marcinkowska M, Kubacka M, Zagorska A, Jaromin A, Fajkis-Zajaczkowska N, Kolaczkowski M (January 2022). "Exploring the antiplatelet activity of serotonin 5-HT2A receptor antagonists bearing 6-fluorobenzo[d]isoxazol-3-yl)propyl) motif- as potential therapeutic agents in the prevention of cardiovascular diseases". Biomedicine & Pharmacotherapy. 145: 112424. doi:10.1016/j.biopha.2021.112424. PMID 34785417. S2CID 244111116.
  105. ^ Nilsson T, Longmore J, Shaw D, Pantev E, Bard JA, Branchek T, et al. (May 1999). "Characterisation of 5-HT receptors in human coronary arteries by molecular and pharmacological techniques". European Journal of Pharmacology. 372 (1): 49–56. doi:10.1016/S0014-2999(99)00114-4. PMID 10374714.
  106. ^ Nagatomo T, Rashid M, Abul Muntasir H, Komiyama T (October 2004). "Functions of 5-HT2A receptor and its antagonists in the cardiovascular system". Pharmacology & Therapeutics. 104 (1): 59–81. doi:10.1016/j.pharmthera.2004.08.005. PMID 15500909.
  107. ^ Weiner DM, Burstein ES, Nash N, Croston GE, Currier EA, Vanover KE, et al. (October 2001). "5-hydroxytryptamine2A receptor inverse agonists as antipsychotics". The Journal of Pharmacology and Experimental Therapeutics. 299 (1): 268–276. PMID 11561089.
  108. ^ Vanover KE, Harvey SC, Son T, Bradley SR, Kold H, Makhay M, et al. (September 2004). "Pharmacological characterization of AC-90179 [2-(4-methoxyphenyl)-N-(4-methyl-benzyl)-N-(1-methyl-piperidin-4-yl)-acetamide hydrochloride]: a selective serotonin 2A receptor inverse agonist". The Journal of Pharmacology and Experimental Therapeutics. 310 (3): 943–951. doi:10.1124/jpet.104.066688. PMID 15102927. S2CID 12205122.
  109. ^ Rosenberg R, Seiden DJ, Hull SG, Erman M, Schwartz H, Anderson C, et al. (December 2008). "APD125, a selective serotonin 5-HT(2A) receptor inverse agonist, significantly improves sleep maintenance in primary insomnia". Sleep. 31 (12): 1663–1671. doi:10.1093/sleep/31.12.1663. PMC 2603489. PMID 19090322.
  110. ^ Vanover KE, Weiner DM, Makhay M, Veinbergs I, Gardell LR, Lameh J, et al. (May 2006). "Pharmacological and behavioral profile of N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl) carbamide (2R,3R)-dihydroxybutanedioate (2:1) (ACP-103), a novel 5-hydroxytryptamine(2A) receptor inverse agonist". The Journal of Pharmacology and Experimental Therapeutics. 317 (2): 910–918. doi:10.1124/jpet.105.097006. PMID 16469866. S2CID 22681576.
  111. ^ Gardell LR, Vanover KE, Pounds L, Johnson RW, Barido R, Anderson GT, et al. (August 2007). "ACP-103, a 5-hydroxytryptamine 2A receptor inverse agonist, improves the antipsychotic efficacy and side-effect profile of haloperidol and risperidone in experimental models". The Journal of Pharmacology and Experimental Therapeutics. 322 (2): 862–870. doi:10.1124/jpet.107.121715. PMID 17519387. S2CID 28861527.
  112. ^ Vanover KE, Betz AJ, Weber SM, Bibbiani F, Kielaite A, Weiner DM, et al. (October 2008). "A 5-HT2A receptor inverse agonist, ACP-103, reduces tremor in a rat model and levodopa-induced dyskinesias in a monkey model". Pharmacology, Biochemistry, and Behavior. 90 (4): 540–544. doi:10.1016/j.pbb.2008.04.010. PMC 2806670. PMID 18534670.
  113. ^ Abbas A, Roth BL (December 2008). "Pimavanserin tartrate: a 5-HT2A inverse agonist with potential for treating various neuropsychiatric disorders". Expert Opinion on Pharmacotherapy. 9 (18): 3251–3259. doi:10.1517/14656560802532707. PMID 19040345. S2CID 71240383.
  114. ^ Office of the Commissioner (10 September 2019). "FDA approves first drug to treat hallucinations and delusions associated with Parkinson's disease". FDA.
  115. ^ Moya PR, Berg KA, Gutiérrez-Hernandez MA, Sáez-Briones P, Reyes-Parada M, Cassels BK, et al. (June 2007). "Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors". The Journal of Pharmacology and Experimental Therapeutics. 321 (3): 1054–1061. doi:10.1124/jpet.106.117507. PMID 17337633. S2CID 11651502.
  116. ^ González-Maeso J, Weisstaub NV, Zhou M, Chan P, Ivic L, Ang R, et al. (February 2007). "Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior". Neuron. 53 (3): 439–452. doi:10.1016/j.neuron.2007.01.008. PMID 17270739. S2CID 16309730.
  117. ^ Cussac D, Boutet-Robinet E, Ailhaud MC, Newman-Tancredi A, Martel JC, Danty N, et al. (October 2008). "Agonist-directed trafficking of signalling at serotonin 5-HT2A, 5-HT2B and 5-HT2C-VSV receptors mediated Gq/11 activation and calcium mobilisation in CHO cells". European Journal of Pharmacology. 594 (1–3): 32–38. doi:10.1016/j.ejphar.2008.07.040. PMID 18703043.
  118. ^ Schmid CL, Raehal KM, Bohn LM (January 2008). "Agonist-directed signaling of the serotonin 2A receptor depends on beta-arrestin-2 interactions in vivo". Proceedings of the National Academy of Sciences of the United States of America. 105 (3): 1079–1084. doi:10.1073/pnas.0708862105. PMC 2242710. PMID 18195357.
  119. ^ Abbas A, Roth BL (January 2008). "Arresting serotonin". Proceedings of the National Academy of Sciences of the United States of America. 105 (3): 831–832. Bibcode:2008PNAS..105..831A. doi:10.1073/pnas.0711335105. PMC 2242676. PMID 18195368.
  120. ^ Zhang G, Cheng J, McCorvy JD, Lorello PJ, Caldarone BJ, Roth BL, et al. (July 2017). "Discovery of N-Substituted (2-Phenylcyclopropyl)methylamines as Functionally Selective Serotonin 2C Receptor Agonists for Potential Use as Antipsychotic Medications". Journal of Medicinal Chemistry. 60 (14): 6273–6288. doi:10.1021/acs.jmedchem.7b00584. PMC 7374938. PMID 28657744.
  121. ^ Bonis J, Furlong LI, Sanz F (October 2006). "OSIRIS: a tool for retrieving literature about sequence variants". Bioinformatics. 22 (20): 2567–2569. doi:10.1093/bioinformatics/btl421. PMID 16882651. Supplementary material to article
  122. ^ Goldstein AT, Pukall C, Goldstein IL (2020). "Fibromyalgia and Female Sexual Pain Disorders". Female Sexual Pain Disorders: Evaluation and Management (2 ed.). Wiley. ISBN 978-1119482666.
  123. ^ a b c d Ruble CL, Smith RM, Calley J, Munsie L, Airey DC, Gao Y, et al. (January 2016). "Genomic structure and expression of the human serotonin 2A receptor gene (HTR2A) locus: identification of novel HTR2A and antisense (HTR2A-AS1) exons". BMC Genetics. 17 (1): 16. doi:10.1186/s12863-015-0325-6. PMC 4702415. PMID 26738766.
  124. ^ Medrihan L, Sagi Y, Inde Z, Krupa O, Daniels C, Peyrache A, et al. (August 2017). "Initiation of Behavioral Response to Antidepressants by Cholecystokinin Neurons of the Dentate Gyrus". Neuron. 95 (3): 564–576.e4. doi:10.1016/j.neuron.2017.06.044. PMID 28735749.
  125. ^ Griffin A, Hamling KR, Knupp K, Hong S, Lee LP, Baraban SC (March 2017). "Clemizole and modulators of serotonin signalling suppress seizures in Dravet syndrome". Brain. 140 (3): 669–683. doi:10.1093/brain/aww342. PMC 6075536. PMID 28073790.
  126. ^ Giulietti M, Vivenzio V, Piva F, Principato G, Bellantuono C, Nardi B (July 2014). "How much do we know about the coupling of G-proteins to serotonin receptors?". Molecular Brain. 7 (1): 49. doi:10.1186/s13041-014-0049-y. PMC 4105882. PMID 25011628.
  127. ^ Lal D, May P, Perez-Palma E, Samocha KE, Kosmicki JA, Robinson EB, et al. (March 2020). "Gene family information facilitates variant interpretation and identification of disease-associated genes in neurodevelopmental disorders". Genome Medicine. 12 (1): 28. doi:10.1186/s13073-020-00725-6. PMC 7079346. PMID 32183904.
  128. ^ Gao W, Guo N, Zhao S, Chen Z, Zhang W, Yan F, et al. (November 2020). "HTR2A promotes the development of cardiac hypertrophy by activating PI3K-PDK1-AKT-mTOR signaling". Cell Stress & Chaperones. 25 (6): 899–908. doi:10.1007/s12192-020-01124-x. PMC 7591670. PMID 32519137.
  129. ^ Cao X, Wang Y, Shu D, Qu H, Luo C, Hu X (October 2020). "Food intake-related genes in chicken determined through combinatorial genome-wide association study and transcriptome analysis". Animal Genetics. 51 (5): 741–751. doi:10.1111/age.12980. PMID 32720725. S2CID 220839883.
  130. ^ Garza-Brenner E, Sifuentes-Rincón AM, Randel RD, Paredes-Sánchez FA, Parra-Bracamonte GM, Arellano Vera W, et al. (August 2017). "Association of SNPs in dopamine and serotonin pathway genes and their interacting genes with temperament traits in Charolais cows". Journal of Applied Genetics. 58 (3): 363–371. doi:10.1007/s13353-016-0383-0. PMID 27987181. S2CID 34463383.
  131. ^ Cheah SY, Lawford BR, Young RM, Morris CP, Voisey J (January 2017). "mRNA Expression and DNA Methylation Analysis of Serotonin Receptor 2A (HTR2A) in the Human Schizophrenic Brain". Genes. 8 (1): 14. doi:10.3390/genes8010014. PMC 5295009. PMID 28054990.
  132. ^ Falkenberg VR, Gurbaxani BM, Unger ER, Rajeevan MS (March 2011). "Functional genomics of serotonin receptor 2A (HTR2A): interaction of polymorphism, methylation, expression and disease association". Neuromolecular Medicine. 13 (1): 66–76. doi:10.1007/s12017-010-8138-2. PMC 3044825. PMID 20941551.
  133. ^ Kelemen O, Convertini P, Zhang Z, Wen Y, Shen M, Falaleeva M, et al. (February 2013). "Function of alternative splicing". Gene. 514 (1): 1–30. doi:10.1016/j.gene.2012.07.083. PMC 5632952. PMID 22909801.
  134. ^ Wang ET, Ward AJ, Cherone JM, Giudice J, Wang TT, Treacy DJ, et al. (June 2015). "Antagonistic regulation of mRNA expression and splicing by CELF and MBNL proteins". Genome Research. 25 (6): 858–871. doi:10.1101/gr.184390.114. PMC 4448682. PMID 25883322.
  135. ^ Choi MJ, Lee HJ, Lee HJ, Ham BJ, Cha JH, Ryu SH, et al. (2004). "Association between major depressive disorder and the -1438A/G polymorphism of the serotonin 2A receptor gene". Neuropsychobiology. 49 (1): 38–41. doi:10.1159/000075337. PMID 14730199. S2CID 19528052.
  136. ^ Williams J, Spurlock G, McGuffin P, Mallet J, Nöthen MM, Gill M, et al. (May 1996). "Association between schizophrenia and T102C polymorphism of the 5-hydroxytryptamine type 2a-receptor gene. European Multicentre Association Study of Schizophrenia (EMASS) Group". Lancet. 347 (9011): 1294–1296. doi:10.1016/s0140-6736(96)90939-3. PMID 8622505. S2CID 8510590.
  137. ^ Vaquero-Lorenzo C, Baca-Garcia E, Diaz-Hernandez M, Perez-Rodriguez MM, Fernandez-Navarro P, Giner L, et al. (July 2008). "Association study of two polymorphisms of the serotonin-2A receptor gene and suicide attempts". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 147B (5): 645–649. doi:10.1002/ajmg.b.30642. PMID 18163387. S2CID 31504282.
  138. ^ Gene Overview of All Published Schizophrenia-Association Studies for HTR2A Archived 21 February 2009 at the Wayback Machine – SzGene database at Schizophrenia Research Forum.
  139. ^ Serretti A, Drago A, De Ronchi D (2007). "HTR2A gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies". Current Medicinal Chemistry. 14 (19): 2053–2069. doi:10.2174/092986707781368450. PMID 17691947.
  140. ^ Maple AM, Zhao X, Elizalde DI, McBride AK, Gallitano AL (July 2015). "Htr2a Expression Responds Rapidly to Environmental Stimuli in an Egr3-Dependent Manner". ACS Chemical Neuroscience. 6 (7): 1137–1142. doi:10.1021/acschemneuro.5b00031. PMC 4565721. PMID 25857407.
  141. ^ a b Williams AA, Ingram WM, Levine S, Resnik J, Kamel CM, Lish JR, et al. (September 2012). "Reduced levels of serotonin 2A receptors underlie resistance of Egr3-deficient mice to locomotor suppression by clozapine". Neuropsychopharmacology. 37 (10): 2285–2298. doi:10.1038/npp.2012.81. PMC 3422493. PMID 22692564.
  142. ^ Latorre E, Mesonero JE, Harries LW (November 2019). "Alternative splicing in serotonergic system: Implications in neuropsychiatric disorders". Journal of Psychopharmacology. 33 (11): 1352–1363. doi:10.1177/0269881119856546. PMID 31210090. S2CID 190531249.
  143. ^ Spies M, Nasser A, Ozenne B, Jensen PS, Knudsen GM, Fisher PM (November 2020). "Common HTR2A variants and 5-HTTLPR are not associated with human in vivo serotonin 2A receptor levels". Human Brain Mapping. 41 (16): 4518–4528. doi:10.1002/hbm.25138. PMC 7555071. PMID 32697408.
  144. ^ Qesseveur G, Petit AC, Nguyen HT, Dahan L, Colle R, Rotenberg S, et al. (June 2016). "Genetic dysfunction of serotonin 2A receptor hampers response to antidepressant drugs: A translational approach". Neuropharmacology. 105: 142–153. doi:10.1016/j.neuropharm.2015.12.022. PMID 26764241. S2CID 15031564.
  145. ^ Ghasemi A, Seifi M, Baybordi F, Danaei N, Samadi Rad B (June 2018). "Association between serotonin 2A receptor genetic variations, stressful life events and suicide". Gene. 658: 191–197. doi:10.1016/j.gene.2018.03.023. PMID 29526601. S2CID 4854262.
  146. ^ Videtic A, Pungercic G, Pajnic IZ, Zupanc T, Balazic J, Tomori M, et al. (September 2006). "Association study of seven polymorphisms in four serotonin receptor genes on suicide victims". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 141B (6): 669–672. doi:10.1002/ajmg.b.30390. PMID 16856120. S2CID 9279191.
  147. ^ Laje G, McMahon FJ (December 2007). "The pharmacogenetics of major depression: past, present, and future". Biological Psychiatry. 62 (11): 1205–1207. doi:10.1016/j.biopsych.2007.09.016. PMID 17949692. S2CID 37225993.
  148. ^ Leamy TE, Connor JP, Voisey J, Young RM, Gullo MJ (December 2016). "Alcohol misuse in emerging adulthood: Association of dopamine and serotonin receptor genes with impulsivity-related cognition". Addictive Behaviors. 63: 29–36. doi:10.1016/j.addbeh.2016.05.008. PMID 27399274.
  149. ^ Jakubczyk A, Wrzosek M, Lukaszkiewicz J, Sadowska-Mazuryk J, Matsumoto H, Sliwerska E, et al. (January 2012). "The CC genotype in HTR2A T102C polymorphism is associated with behavioral impulsivity in alcohol-dependent patients". Journal of Psychiatric Research. 46 (1): 44–49. doi:10.1016/j.jpsychires.2011.09.001. PMC 3224206. PMID 21930285.
  150. ^ da Silva Junior FC, Araujo RM, Sarmento AS, de Carvalho MM, Fernandes HF, Yoshioka FK, et al. (December 2020). "The association of A-1438G and T102C polymorphisms in HTR2A and 120 bp duplication in DRD4 with alcoholic dependence in a northeastern Brazilian male population". Gene Reports. 21: 100889. doi:10.1016/j.genrep.2020.100889. S2CID 224859807.
  151. ^ Land MA, Ramesh D, Miller AL, Pyles RB, Cunningham KA, Moeller FG, et al. (10 June 2020). "Methylation Patterns of the HTR2A Associate With Relapse-Related Behaviors in Cocaine-Dependent Participants". Frontiers in Psychiatry. 11: 532. doi:10.3389/fpsyt.2020.00532. PMC 7299072. PMID 32587535.
  152. ^ Lemaire C, Cantineau R, Guillaume M, Plenevaux A, Christiaens L (December 1991). "Fluorine-18-altanserin: a radioligand for the study of serotonin receptors with PET: radiolabeling and in vivo biologic behavior in rats". Journal of Nuclear Medicine. 32 (12): 2266–2272. PMID 1744713.
  153. ^ Lundkvist C, Halldin C, Ginovart N, Nyberg S, Swahn CG, Carr AA, et al. (1996). "[11C]MDL 100907, a radioligland for selective imaging of 5-HT(2A) receptors with positron emission tomography". Life Sciences. 58 (10): PL 187-PL 192. doi:10.1016/0024-3205(96)00013-6. PMID 8602111.
  154. ^ Johansen A, Hansen HD, Svarer C, Lehel S, Leth-Petersen S, Kristensen JL, et al. (April 2018). "The importance of small polar radiometabolites in molecular neuroimaging: A PET study with [11C]Cimbi-36 labeled in two positions". Journal of Cerebral Blood Flow and Metabolism. 38 (4): 659–668. doi:10.1177/0271678x17746179. PMC 5888860. PMID 29215308.
  155. ^ Mintun MA, Sheline YI, Moerlein SM, Vlassenko AG, Huang Y, Snyder AZ (February 2004). "Decreased hippocampal 5-HT2A receptor binding in major depressive disorder: in vivo measurement with [18F]altanserin positron emission tomography". Biological Psychiatry. 55 (3): 217–224. doi:10.1016/j.biopsych.2003.08.015. PMID 14744461. S2CID 24849671.
  156. ^ Rosier A, Dupont P, Peuskens J, Bormans G, Vandenberghe R, Maes M, et al. (November 1996). "Visualisation of loss of 5-HT2A receptors with age in healthy volunteers using [18F]altanserin and positron emission tomographic imaging". Psychiatry Research. 68 (1): 11–22. doi:10.1016/S0925-4927(96)02806-5. PMID 9027929. S2CID 32317795.
  157. ^ Meltzer CC, Smith G, Price JC, Reynolds CF, Mathis CA, Greer P, et al. (November 1998). "Reduced binding of [18F]altanserin to serotonin type 2A receptors in aging: persistence of effect after partial volume correction". Brain Research. 813 (1): 167–171. doi:10.1016/S0006-8993(98)00909-3. PMID 9824691. S2CID 21884218.
  158. ^ Adams KH, Pinborg LH, Svarer C, Hasselbalch SG, Holm S, Haugbøl S, et al. (March 2004). "A database of [(18)F]-altanserin binding to 5-HT(2A) receptors in normal volunteers: normative data and relationship to physiological and demographic variables". NeuroImage. 21 (3): 1105–1113. doi:10.1016/j.neuroimage.2003.10.046. PMID 15006678. S2CID 24403109.

Further reading

  • "5-HT2A". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
Quelle: https://en.wikipedia.org/wiki/5HT2A