Serotonin (5-hydroxytryptamine, 5-HT) plays unequivocally a most important role in the normal physiology amongst higher eukaryotes, as do most neurotransmitters. The physiological roles of serotonin and its receptors range from appetite, regulation of the circadian rhythm, sexual behavior, memory and nociception. Serotonin is also involved in migraine and some psychiatric diseases such as depression anxiety and aggression¹. Serotonin and its receptors also have an influence on the cardiovascular, pulmonary, gastrointestinal (GI) and genitourinary systems².

To date, some fifteen serotonin receptors have been cloned and grouped into seven families (5-HT1-5-HT7) based on their signaling mechanisms. The 5-HT1 receptor class comprises 5 different receptors with ranging homology. Apart from 5-HT3, all serotonin receptors belong to the G-protein coupled receptor superfamily and therefore span the membrane seven times³.

Members of the 5-HT1 receptor class all couple G_i/0 thereby inhibiting adenylate cyclase.

In the central nervous system, 5-HT1D is expressed in the basal ganglia, hippocampus and cortex in the rat and in the basal ganglia, midbrain and spinal cord in the human. In serotonin neurons, 5-HT1D receptors are autoreceptors thereby inhibiting the release of 5-HT. In GABA, ACh, and glutamate neurons they are heteroreceptors where they control the release of these neurotransmitters^4,5.

The serotonin system plays an undeniable role in the perception and processing of pain. Indeed, many migraine sufferers are prescribed triptan-based drugs which activate 5-HT1B and 5-HT1D receptors².