SEROTONIN AND SEROTONIN ANTAGONISM IN CARDIOVASCULAR AND NON-CARDIOVASCULAR DISEASE

Serotonin, or 5-hydroxytryptamine, is a naturally-occurring vasoactive substance found primarily in the brain, enterochromaffin tissue, and blood platelets. It has diffuse cardiophysiologic effects. The multipl e effects of serotonin on blood vessels can be explained by the existe nce of 2 serotonergic receptor subtypes (the S-1 receptor mediates vas odilation, and the S-2 receptor vasoconstriction). Serotonin via the S -2 receptor also augments the actions of several other vasoconstrictin g substances. Serotonin may be responsible for causing, or at least pe rpetuating, some forms of systemic hypertension through peripheral and central nervous system (CNS) actions. Ketanserin is a highly selectiv e S-2-serotonergic antagonist with additional alpha-adrenergic blockin g activity, which has been proposed as a therapy for various cardiovas cular diseases including hypertension. It has been shown to be more ef fective than placebo in treating hypertension and comparable in effect iveness to other antihypertensive drugs. Its major side effects relate to the CNS, and prolongation of the electrocardiogram QT interval has been described. Caution must be used when using ketanserin in patient s receiving potassium- and magnesium-losing agents, because of the ris k of torsades de pointes. Ketanserin has potential utility in the trea tment of eclampsia, peripheral vascular disease, carcinoid syndrome, a nd ''shock lung.'' The drug is not yet approved for clinical use in th e United States.