In:
Cephalalgia, SAGE Publications, Vol. 12, No. 4 ( 1992-08), p. 187-196
Abstract:
After the synthetic serotonin 5-hydroxytryptamine (5-HT) became available in the early 1950s, attempts were soon under way to study the nature of 5-HT receptors. Using the guinea-pig isolated ileum, Gaddum and Picarelli (1957) suggested that 5-HT-induced contractions were mediated by a morphine-sensitive “M” receptor located on the parasympathetic ganglion and a dibenzyline-sensitive “D” receptor located on the smooth muscle. Though this classification was used during the next three decades, it was realized that some effects of serotonin, for example vasoconstriction within the carotid vascular bed, were not mediated by either “M” or “D” receptors. When radioligand binding studies led to the identification of 5-HT 1 and 5-HT 2 “receptors” in the rat brain membranes, it became increasingly apparent that the two receptor classifications were not identical. Thus, a new framework for serotonin receptor nomenclature and classification was proposed: 5-HT 1 -like (5-HT 1 ), 5-HT 2 (formerly “D”) and 5-HT 3 (formerly “M”) receptors. At the present time, several subtypes of 5-HT 1 receptors as well as a 5-HT 4 receptor are also recognized. As the serotonin receptor classification was emerging to indicate that carotid vasoconstriction by serotonin is mediated by a subtype of 5-HT 1 receptors, on the migraine front it was being suggested that the disease is associated with vasodilatation within the cranial extracerebral circulation and deranged serotonin metabolism and that certain antimigraine drugs caused a selective carotid vasoconstriction, probably via serotonin receptors. Therefore, Humphrey and colleagues conceived that synthesis of serotonin derivatives may lead to a compound that would elicit highly selective carotid vasoconstriction and abort migraine attacks. Indeed, via the synthesis of 5-carboxamidotryptamine and AH25086, sumatriptan was designed. The drug acts as an agonist at the vasoconstrictor 5-HT 1 receptor subtype and has proved highly effective in the therapy of migraine attacks.
Type of Medium:
Online Resource
ISSN:
0333-1024
,
1468-2982
DOI:
10.1046/j.1468-2982.1992.1204187.x
Language:
English
Publisher:
SAGE Publications
Publication Date:
1992
detail.hit.zdb_id:
2019999-5
