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5-HT1D receptor agonists also known as triptans, share the common pharmacology of being non-selective 5-HT1D/1B receptor agonists that are located mainly in the hippocampus, basal ganglia, cortex, spinal cord and vascular smooth muscle cells.〔McCall, R. B., et al. (2002). "Preclinical studies characterizing the anti-migraine and cardiovascular effects of the selective 5-HT1D receptor agonist PNU-142633." Cephalalgia 22(10): 799-806〕 5-HT1D receptor agonists bind to 5-HT1D/1B receptors with nearly identical affinity, but they also bind to 5-HT1F receptors.〔Lippincott, W. W., Lemke, T. L., Williams, D. A., Roche, V. F., & Zito, S. W. (2013). Foye's Principles of Medicinal Chemistry: Lippincott Williams & Wilkins: 368-376.〕 5-HT1D receptor agonists or triptans are a class of drugs that works as endogenous neurotransmitters by blocking 5-HT1D/1B receptors. The triptan drugs including sumatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, frovatriptan, naratriptan, donitriptan and alniditan commonly share an activity in the trigeminovascular system and most of them share a similar binding profile.〔 Triptans has shown to be clinically effective in the treatment of migraine and are today used as headache medications. However, triptans have no effect on pain as such. The mechanism of action is still not clear and most of the knowledge on mechanism of action comes from animal studies.〔Kroger, I. L. and A. May (2015). "Triptan-induced disruption of trigemino-cortical connectivity." Neurology 84(21): 2124-2131〕 ==History and development== The history of 5-HT1D receptor agonists began with the proposed existence of then unknown Serotonin (5-HT). It was in the late 1940s when two groups of investigators one in Italy and the other in United States (US) identified substance called serotonin in the US and enteramine in Italy. In the early 1950s it was confirmed that both substances were the same. Later it was to be discovered in both animals and plants. In the mid-1950s it was discovered in the central nervous system (CNS) of animals and was proposed to have a role as a neurotransmitter. Experimental on mechanism of action were not very successful and experimental techniques were lacking for the investigation of 5-HT action.〔 It became available for clinical use in 1991 and was initially launched in Holland. In late 1972 Patrick P.A. Humphrey was given the task of finding an anti-migraine drug at Glaxo. Patrick had been interested in Harold Wolff’s proposed vascular theory of migraine and kept going on with the science of migraine. Former studies in the 1960s showed that vasoconstriction caused by 5-HT, noradrenaline and ergotamine could reduce migraine attacks. Patrick among others started researching the 5-HT receptor to discover a more direct 5-HT agonist with fewer side-effects. The discovery of sumatriptan began with the developing of a compound that was proposed to be a vasoconstrictor in the carotid circulation, but instead it caused vasodilation. Several years went by while working on characterizing 5-HT receptors throughout the body in different species. They found out about a new receptor, now known as the 5-HT1 receptor that was located on cranial blood vessels. They continued developing and working on a desirable action on 5-HT by 5-HT1 receptor activation for an anti-migraine drug. Continued work led to the development of sumatriptan now known as the first 5-HT1 agonist, selective for 5-HT1D/B receptor and also 5-HT1F receptor with less affinity. By 1991 sumatriptan became available in clinically use in Holland and in the US in 1993. However, there was always debate about mechanism of action of sumatriptan and still remains unclear today. Later on Mike Moskowitz proposed a theory about "neuronal extravasation" and this was the first clue that sumatriptan might have a direct neuronal effect in migraine attacks.〔Humphrey, P. P. (2007). "The discovery of a new drug class for the acute treatment of migraine." Headache 47 Suppl 1: S10-19.〕 Later on sumatriptan became a prototype for other 5-HT1D receptor agonists that have been developed for improved selectivity for the 5-HT1D receptors.〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「5-HT1D receptor agonist」の詳細全文を読む スポンサード リンク
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