5-HT1D receptor

5HT_1D receptors are found at low levels in the basal ganglia (globus pallidus, substantia nigra, caudate putamen), the hippocampus, and in the cortex.{{cite book | vauthors = Hoyer D | chapter = Serotonin receptors nomenclature | veditors = Tricklebank MD, Daly E | title = The Serotonin System: History, Neuropharmacology, and Pathology | publisher = Academic Press |date=2019 |pages=63–93 | isbn = 978-0-12-813323-1 |doi=10.1016/B978-0-12-813323-1.00004-9}}

5HT_1D receptor is a G protein linked receptor that activates an intracellular messenger cascade to produce an inhibitory response by decreasing cellular levels of cAMP.{{cite journal | vauthors = Millan MJ, Marin P, Bockaert J, Mannoury la Cour C | title = Signaling at G-protein-coupled serotonin receptors: recent advances and future research directions | journal = Trends in Pharmacological Sciences | volume = 29 | issue = 9 | pages = 454–64 | date = September 2008 | pmid = 18676031 | doi = 10.1016/j.tips.2008.06.007 }}{{cite journal | vauthors = Goadsby PJ |title=Serotonin 5-HT_1B/1D Receptor Agonists in Migraine: Comparative Pharmacology and Its Therapeutic Implications |journal=CNS Drugs |date=1998 |volume=10 |issue=4 |pages=271–286 |doi=10.2165/00023210-199810040-00005}} The 5HT_1D is a 7-TM receptor. A large intercellular loop between TM-5 and TM-6 is believed to be associated with coupling to a second messenger. Agonists might bind in a manner that utilizes an aspartate residue in TM-3 and residues in the TM-4, TM-5 and TM-6.{{cite book | vauthors = Glennon RA, Dukat M | chapter = Serotonin Receptors and Drugs Affecting Serotonergic Neurotransmission | chapter-url = https://downloads.lww.com/wolterskluwer_vitalstream_com/sample-content/9781609133450_Lemke/samples/Chapter_11.pdf | veditors = Lippincott WW, Lemke TL, Williams DA, Roche VF, Zito SW |title=Foye's Principles of Medicinal Chemistry |date=2013 |publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins |location=Philadelphia |isbn=978-1-60913-345-0 |edition=7th | pages = 368-376 }} A human clone containing an intronless open reading frame was found to encode 377 amino acids of the 5HT_1D receptor. The gene has been localized on chromosome 1, region 1p34.3-36.3 {{cite journal | vauthors = Jin H, Oksenberg D, Ashkenazi A, Peroutka SJ, Duncan AM, Rozmahel R, Yang Y, Mengod G, Palacios JM, O'Dowd BF | title = Characterization of the human 5-hydroxytryptamine1B receptor | journal = The Journal of Biological Chemistry | volume = 267 | issue = 9 | pages = 5735–5738 | date = March 1992 | pmid = 1348246 | doi = 10.1016/S0021-9258(18)42612-9 | doi-access = free }}{{cite journal | vauthors = Weinshank RL, Zgombick JM, Macchi MJ, Branchek TA, Hartig PR | title = Human serotonin 1D receptor is encoded by a subfamily of two distinct genes: 5-HT1D alpha and 5-HT1D beta | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 8 | pages = 3630–3634 | date = April 1992 | pmid = 1565658 | pmc = 48922 | doi = 10.1073/pnas.89.8.3630 | doi-access = free | bibcode = 1992PNAS...89.3630W }}

Molecular modelling has provided a picture of the agonistic binding site of 5HT_1D. The amino acid residues within the receptor binding site region have been identified. This is a valuable guide to design potential 5HT_1D receptor agonists.

When sumatriptan binds there is major conformational change in both ligand and receptor in the binding pocket.{{cite journal | vauthors = Bremner DH, Ringan NS, Wishart G | year = 1997 | title = Modeling of the agonist binding site of serotonin human 5-HT_1A, 5-HT_1Dα and 5-HT_1Dβ receptors | journal = European Journal of Medicinal Chemistry | volume = 32 | issue = 1| pages = 59–69 | doi = 10.1016/S0223-5234(97)84362-0 }}

• 5-(Nonyloxy)tryptamine{{cite journal | vauthors = Glennon RA, Hong SS, Dukat M, Teitler M, Davis K | title = 5-(Nonyloxy)tryptamine: a novel high-affinity 5-HT1D beta serotonin receptor agonist | journal = Journal of Medicinal Chemistry | volume = 37 | issue = 18 | pages = 2828–2830 | date = September 1994 | pmid = 8071931 | doi = 10.1021/jm00044a001 }}
• Sumatriptan (vasoconstrictor in migraine)
• Ergotamine (vasoconstrictor in migraine)
• Zolmitriptan
• 5-Carboxamidotryptamine (5-CT)
• 5-(t-Butyl)-N-methyltryptamine{{cite journal | vauthors = Xu YC, Schaus JM, Walker C, Krushinski J, Adham N, Zgombick JM, Liang SX, Kohlman DT, Audia JE | title = N-Methyl-5-tert-butyltryptamine: A novel, highly potent 5-HT1D receptor agonist | journal = Journal of Medicinal Chemistry | volume = 42 | issue = 3 | pages = 526–531 | date = February 1999 | pmid = 9986723 | doi = 10.1021/jm9805945 }}
• CP-135807
• CP-286601
• PNU-109291 ((S)-3,4-Dihydro-1-[2-[4-(4-methoxyphenyl)-1-piperazinyl]ethyl]-N-methyl-1H-2-benzopyran-6-carboxamide)
• PNU-142633 ((1S)-1-[2-[4-[4-(Aminocarbonyl)phenyl]-1-piperazinyl]ethyl]-3,4-dihydro-N-methyl-1H-2-benzopyran-6-carboxamide)
• GR-46611 (3-[3-(2-Dimethylaminoethyl)-1H-indol-5-yl]-N-(4-methoxybenzyl)acrylamide)
• L-694247 (2-[5-[3-(4-Methylsulfonylamino)benzyl-1,2,4-oxadiazol-5-yl]-1H-indol-3-yl]ethanamine)
• L-760790
• L-772405

• Ziprasidone (atypical antipsychotic) [https://books.google.com/books?id=HkA0Q31YDhAC&dq=antipsychotics+5ht1d&pg=PA438]
• Methiothepin (antipsychotic)
• Yohimbine (aphrodisiac)
• Metergoline
• BRL-15572
• Vortioxetine (antidepressant)
• GR-127935 (mixed 5-HT_1B/1D antagonist)
• LY-310762
• LY-367642
• LY-456219
• LY-456220

• 5-HT₁ receptor
• 5-HT receptor

{{reflist|35em}}

• {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2314 | title = 5-HT_1D | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology }}
• {{UCSC gene info|HTR1D}}

{{refbegin | 2}}

• {{cite journal | vauthors = Hamblin MW, Metcalf MA, McGuffin RW, Karpells S | title = Molecular cloning and functional characterization of a human 5-HT1B serotonin receptor: a homologue of the rat 5-HT1B receptor with 5-HT1D-like pharmacological specificity | journal = Biochemical and Biophysical Research Communications | volume = 184 | issue = 2 | pages = 752–759 | date = April 1992 | pmid = 1315531 | doi = 10.1016/0006-291X(92)90654-4 }}
• {{cite journal | vauthors = Weinshank RL, Zgombick JM, Macchi MJ, Branchek TA, Hartig PR | title = Human serotonin 1D receptor is encoded by a subfamily of two distinct genes: 5-HT1D alpha and 5-HT1D beta | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 8 | pages = 3630–3634 | date = April 1992 | pmid = 1565658 | pmc = 48922 | doi = 10.1073/pnas.89.8.3630 | doi-access = free | bibcode = 1992PNAS...89.3630W }}
• {{cite journal | vauthors = Hamblin MW, Metcalf MA | title = Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor | journal = Molecular Pharmacology | volume = 40 | issue = 2 | pages = 143–148 | date = August 1991 | pmid = 1652050 }}
• {{cite journal | vauthors = Libert F, Passage E, Parmentier M, Simons MJ, Vassart G, Mattei MG | title = Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor | journal = Genomics | volume = 11 | issue = 1 | pages = 225–227 | date = September 1991 | pmid = 1662665 | doi = 10.1016/0888-7543(91)90125-X }}
• {{cite journal | vauthors = Libert F, Parmentier M, Lefort A, Dinsart C, Van Sande J, Maenhaut C, Simons MJ, Dumont JE, Vassart G | title = Selective amplification and cloning of four new members of the G protein-coupled receptor family | journal = Science | volume = 244 | issue = 4904 | pages = 569–572 | date = May 1989 | pmid = 2541503 | doi = 10.1126/science.2541503 | bibcode = 1989Sci...244..569L }}
• {{cite journal | vauthors = Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES | title = Characterization of single-nucleotide polymorphisms in coding regions of human genes | journal = Nature Genetics | volume = 22 | issue = 3 | pages = 231–238 | date = July 1999 | pmid = 10391209 | doi = 10.1038/10290 | s2cid = 195213008 }}
• {{cite journal | vauthors = Salim K, Fenton T, Bacha J, Urien-Rodriguez H, Bonnert T, Skynner HA, Watts E, Kerby J, Heald A, Beer M, McAllister G, Guest PC | title = Oligomerization of G-protein-coupled receptors shown by selective co-immunoprecipitation | journal = The Journal of Biological Chemistry | volume = 277 | issue = 18 | pages = 15482–15485 | date = May 2002 | pmid = 11854302 | doi = 10.1074/jbc.M201539200 | doi-access = free | url = https://kar.kent.ac.uk/61530/1/J.%20Biol.%20Chem.-2002-Salim-15482-5.pdf }}
• {{cite journal | vauthors = Bergen AW, van den Bree MB, Yeager M, Welch R, Ganjei JK, Haque K, Bacanu S, Berrettini WH, Grice DE, Goldman D, Bulik CM, Klump K, Fichter M, Halmi K, Kaplan A, Strober M, Treasure J, Woodside B, Kaye WH | title = Candidate genes for anorexia nervosa in the 1p33-36 linkage region: serotonin 1D and delta opioid receptor loci exhibit significant association to anorexia nervosa | journal = Molecular Psychiatry | volume = 8 | issue = 4 | pages = 397–406 | date = April 2003 | pmid = 12740597 | doi = 10.1038/sj.mp.4001318 | s2cid = 22413624 }}

{{refend}}

{{NLM content}}

{{G protein-coupled receptors}}

{{Serotonergics}}

{{Obsessive–compulsive disorder}}

{{DEFAULTSORT:5-Ht1d Receptor}}

Category:Serotonin receptors

{{transmembranereceptor-stub}}