Sumatriptan, structure

Sumatriptan and the other triptans are selective agonists for 5-HT1D and 5-HT1B receptors the similarity of the triptan structure to that of the 5-HT nucleus can be seen in the structure below. These receptor types are found in cerebral and meningeal vessels and mediate vasoconstriction. They are also found on neurons and probably function as presynaptic inhibitory receptors. 

Migraine headaches that do not respond to analgesics may be relieved by the use of an agonist of the 5-HT receptor, since these receptors are known to mediate vasoconstriction. Though the causes of migraine are not clear, they are characterized by dilation of cerebral blood vessels. 5-HTi agonists based on the 5-HT structure in current use include the sulphonamide derivative sumatriptan, and the more recent agents naratriptan, rizatriptan,... 

Migraine was a condition that was refractory to treatment until the discovery of the serotonin receptor blocker, such as sumatriptan. This agent was soon followed by several other drugs that acted by the same mechanism. Tidembersat (13) a compound more closely related, both in structure and mechanism of action, to antihypertensive benzopyrans that act on... 

A 34-year-old man with migraine had palpitation after taking sumatriptan by nasal spray for a severe headache (13). A similar episode had occurred after he had previously taken sumatriptan. He had atrial fibrillation with a rapid ventricular rate. Sinus rhythm returned spontaneously within a few hours. No structural cardiac abnormality was detected. 

This review will highlight developments in the structures of ligands for the 5-HTid receptor beyond sumatriptan [58], and will concentrate on the in vitro binding and functional properties of molecules. An excellent review of earlier literatime has appeared [59]. The emphasis will be on receptor agonists, refiecting the current focus of pharmaceutical laboratories, but novel, potent antagonists for the 5-HTiq receptor have been reported, and these structures will be discussed in the final part of the chapter. The binding and functional data quoted in this chapter are from disparate sources and will therefore be only qualitatively comparable. 

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