5HT1D receptors are found at low levels in the basal ganglia (globus pallidus, substantia nigra, caudate putamen), the hippocampus, and in the cortex.[6]
5HT1D receptor is a G protein linked receptor that activates an intracellular messenger cascade to produce an inhibitory response by decreasing cellular levels of cAMP.[7][8] The 5HT1D 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.[9] A human clone containing an intronless open reading frame was found to encode 377 amino acids of the 5HT1D receptor. The gene has been localized on chromosome 1, region 1p34.3-36.3 [10][11]
Molecular modelling has provided a picture of the agonistic binding site of 5HT1D. The amino acid residues within the receptor binding site region have been identified. This is a valuable guide to design potential 5HT1D receptor agonists.
When sumatriptan binds there is major conformational change in both ligand and receptor in the binding pocket.[12]
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^Bremner DH, Ringan NS, Wishart G (1997). "Modeling of the agonist binding site of serotonin human 5-HT1A, 5-HT1Dα and 5-HT1Dβ receptors". European Journal of Medicinal Chemistry. 32 (1): 59–69. doi:10.1016/S0223-5234(97)84362-0.
^Glennon RA, Hong SS, Dukat M, Teitler M, Davis K (September 1994). "5-(Nonyloxy)tryptamine: a novel high-affinity 5-HT1D beta serotonin receptor agonist". Journal of Medicinal Chemistry. 37 (18): 2828–2830. doi:10.1021/jm00044a001. PMID8071931.
^Xu YC, Schaus JM, Walker C, Krushinski J, Adham N, Zgombick JM, et al. (February 1999). "N-Methyl-5-tert-butyltryptamine: A novel, highly potent 5-HT1D receptor agonist". Journal of Medicinal Chemistry. 42 (3): 526–531. doi:10.1021/jm9805945. PMID9986723.
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Hamblin MW, Metcalf MA (August 1991). "Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor". Molecular Pharmacology. 40 (2): 143–148. PMID1652050.
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Libert F, Parmentier M, Lefort A, Dinsart C, Van Sande J, Maenhaut C, et al. (May 1989). "Selective amplification and cloning of four new members of the G protein-coupled receptor family". Science. 244 (4904): 569–572. Bibcode:1989Sci...244..569L. doi:10.1126/science.2541503. PMID2541503.
Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, et al. (July 1999). "Characterization of single-nucleotide polymorphisms in coding regions of human genes". Nature Genetics. 22 (3): 231–238. doi:10.1038/10290. PMID10391209. S2CID195213008.
Bergen AW, van den Bree MB, Yeager M, Welch R, Ganjei JK, Haque K, et al. (April 2003). "Candidate genes for anorexia nervosa in the 1p33-36 linkage region: serotonin 1D and delta opioid receptor loci exhibit significant association to anorexia nervosa". Molecular Psychiatry. 8 (4): 397–406. doi:10.1038/sj.mp.4001318. PMID12740597. S2CID22413624.
