Serotonin (5-hydroxytryptamine, 5-HT), originally discovered as a serum factor plays important roles in regulating diverse biological processes in central and peripheral nervous systems, cardiovascular systems, and gastrointestinal systems (1,2). The 5-HT1D (formerly known as 5-HT1Da) receptor has 63â€¯% overall structural homology with the 5-HT1B receptor and a 77â€¯% amino acid sequence homology in the seven transmembrane domains. In situ hybridization studies have detected highest level of mRNA in primary olfactory cortex, accumbens nucleus, caudate putamen, lateral mammilary nucleus and medial vestibular nucleus. The presence of relatively high levels of 5-HT1D mRNA in the locus coeruleus suggest that, when expressed on nerve terminals, this receptor could modulate the release of catecholamines. The 5-HT1D receptor may function as an autoreceptor. Like 5-HT1B receptors, 5-HT1D receptors also appear to act as heteroreceptors. Acting on the 5-HT1D receptors, 5-HT appears to inhibit release of glutamate from rat cerebellar synaptosomes and acetylcholine from guinea pig hippocampal synaptosomes. It has been suggested that neurogenic inflammation and nociceptive activity within trigemino- vascular afferents. Endothelium-dependent relaxation in the pig coronary artery has been claimed to be mediated by 5-HT1D receptors. Like other members of the 5-HT1 family, 5-HT1D receptors are negatively coupled to adenylate cyclase.