5-HT1A receptor
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RefSeq (protein) | |||||||||
Location (UCSC) | Chr 5: 63.96 – 63.96 Mb | Chr 13: 105.58 – 105.58 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
The serotonin 1A receptor (or 5-HT1A receptor) is a subtype of
Distribution
The 5-HT1A receptor is the most widespread of all the 5-HT receptors. In the
Function
Neuromodulation
5-HT1A
Activation of central 5-HT1A receptors triggers the release or inhibition of
5-HT1A receptor agonists like buspirone[18] and flesinoxan[19] show efficacy in relieving anxiety[20] and depression.[21] Buspirone and tandospirone are currently approved for these indications in different parts of the world. Others such as gepirone,[22] flesinoxan,[19] flibanserin,[23] and naluzotan[24] have also been investigated, though none have been fully developed and approved yet. Some of the atypical antipsychotics like lurasidone[25] and aripiprazole[26] are also partial agonists at the 5-HT1A receptor and are sometimes used in low doses as augmentations to standard antidepressants like the selective serotonin reuptake inhibitors (SSRIs).[27] Mice lacking 5-HT1A receptors altogether (knockout) show increased anxiety but lower depressive-like behaviour.[28]
5-HT1A autoreceptor desensitization and increased 5-HT1A receptor postsynaptic activation via general increases in serotonin levels by serotonin
5-HT1A receptors in the
5-HT1A receptor activation has been shown to increase
The activation of 5-HT1A receptors has been demonstrated to impair certain aspects of
Other effects of 5-HT1A activation that have been observed in scientific research include:
- Decreased aggression[49][50]
- Increased sociability[31]
- Decreased impulsivity[51]
- Inhibition of drug-seeking behavior[52][53][54]
- Facilitation of sex drive and arousal[55][56]
- Inhibition of
- Diminished food intake[59]
- Prolongation of REM sleep latency[60][61]
- Reversal of respiratory depression[62]
Endocrinology
5-HT1A receptor activation induces the
Autoreceptors
5-HT1A receptors can be located on the
This autoreceptor-mediated inhibition of serotonin release has been theorized to be a major factor in the therapeutic lag that is seen with serotonergic antidepressants such as the SSRIs.
Unlike most drugs that elevate extracellular serotonin levels like the SSRIs and MAOIs, SRAs such as
Similarly to SRAs, sufficiently high doses of 5-HT1A receptor agonists also bypass the 5-HT1A autoreceptor-mediated inhibition of serotonin release and therefore increase 5-HT1A postsynaptic receptor activation by directly agonizing the postsynaptic receptors
Ligands
The distribution of 5-HT1A receptors in the
Agonists
Partial agonists
- 2C-B[81]
- 2C-E[81]
- 2C-T-2[81]
- 4C-T-2[81]
- 5-CT
- 5-MT
- 5-MeO-DiPT[81]
- 5-MeO-DMT
- 5-MeO-MiPT[81]
- 5-MeO-TMT[81]
- 6-F-DMT[81]
- Adatanserin
- αET
- Amphetamine [citation needed]
- αMT
- Aripiprazole
- Asenapine
- Bacoside
- Bay R 1531
- Befiradol
- Binospirone
- Brexpiprazole
- Bufotenin
- Buspirone (postsynaptic 5-HT1A)
- Cannabidiol[82]
- Cariprazine
- Clozapine
- cis-LSZ[81]
- Dihydroergotamine
- Dimethyltryptamine
- DiPT[81]
- DOET[81]
- DOI[81]
- DPT[81]
- Ebalzotan
- Eltoprazine
- EMDT[81]
- Ergotamine
- Etoperidone
- F-11,461
- F-12,826
- F-13,714
- F-14,679
- Flesinoxan
- Flibanserin
- Ginkgo biloba[83]
- Gepirone
- Haloperidol
- Lamotrigine
- Ipsapirone
- Limonene
- Lisuride
- Lurasidone
- LY-301,317
- Lysergic acid diethylamide(LSD)
- Mescaline[81]
- 3,4-Methylenedioxyamphetamine (MDA)[81]
- 3,4-Methylenedioxymethamphetamine (MDMA)[84]
- Methylphenidate
- Methysergide
- Naluzotan
- NBUMP
- Nefazodone
- Olanzapine
- Osemozotan (postsynaptic 5-HT1A)
- Perospirone
- Pyrimidinylpiperazine
- Piclozotan
- Psilocin
- Psilocybin
- Quetiapine
- Rauwolscine
- Roxindole
- RR-2B[81]
- RU-24,969
- S-15,535
- Sarizotan
- SS-2C[81]
- SSR-181,507
- Sunepitron
- Tandospirone
- Tiospirone
- Trazodone
- Trifluoromethylphenylpiperazine
- Trimethoxyamphetamine[81]
- Umespirone
- Urapidil
- Vilazodone
- Xaliproden
- Yohimbine[85][86][87][88]
- Zalospirone
- Ziprasidone
Full agonists
- 8-OH-DPAT[89]
- Alnespirone
- Buspirone (presynaptic 5-HT1A)
- Befiradol
- Tetrahydrocannabivarin (THCV)
- Eptapirone
- Lesopitron
- MKC-242
- LY-293,284
- Osemozotan (presynaptic 5-HT1A)
- Repinotan
- U-92,016-A
- Flibanserin
- Vortioxetine
Biased agonists
- HBK-17 – β-arrestin biased agonist[90]
- NLX-204 – 2 preferring agonist[91]
- F-15,599, also known as NLX-101
Antagonists
- Alprenolol
- AV-965
- Binospirone (postsynaptic 5-HT1A)
- BMY-7,378
- Cannabigerol
- Cyanopindolol
- Cyproheptadine
- Dotarizine
- Flopropione
- GR-46,611
- Iodocyanopindolol
- Isamoltane
- Lecozotan
- Mefway
- Methiothepin
- MPPF
- NAN-190
- Nebivolol
- Oxprenolol
- Pindobind
- Pindolol (presynaptic 5-HT1A)
- Propranolol
- Risperidone (weak)
- Robalzotan
- SB-649,915
- SDZ-216,525
- Spiperone
- Spiramide
- Spiroxatrine
- UH-301
- WAY-100,135
- WAY-100,635
- Xylamidine
Allosteric Modulators
- Cholesterol – endogenous PAM[93]
- Oleamide – endogenous PAM[94]
- Zn2+ – endogenous NAM[95]
- AM-2201 – exogenous PAM[96]
Genetics
The 5-HT1A receptor is coded by the HTR1A
Protein-protein interactions
The 5-HT1A receptor has been shown to
Receptor oligomers
The 5-HT1A receptor forms
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000178394 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021721 – Ensembl, May 2017
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- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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- ^ a b Glennon RA, Dukat M, Westkaemper RB (2000-01-01). "Serotonin Receptor Subtypes and Ligands". American College of Neurophyscopharmacology. Archived from the original on 21 April 2008. Retrieved 2008-04-11.
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External links
- "5-HT1A". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2012-09-02. Retrieved 2008-11-24.
- Human HTR1A genome location and HTR1A gene details page in the UCSC Genome Browser.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.