Serotonin and Serotonin Antagonism in Cardiovascular and Non‐Cardiovascular Disease

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<jats:p>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 multiple effects of serotonin on blood vessels can be explained by the existence of 2 serotonergic receptor subtypes (the S<jats:sub>1</jats:sub> receptor mediates vasodilation, and the S<jats:sub>2</jats:sub> receptor vasoconstriction). Serotonin via the S<jats:sub>2</jats:sub> receptor also augments the actions of several other vasoconstricting substances. Serotonin may be responsible for causing, or at least perpetuating, some forms of systemic hypertension through peripheral and central nervous system (CNS) actions. Ketanserin is a highly selective S<jats:sub>2</jats:sub>‐serotonergic antagonist with additional α‐adrenergic blocking activity, which has been proposed as a therapy for various cardiovascular diseases including hypertension. It has been shown to be more effective than placebo in treating hypertension and comparable in effectiveness 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 patients receiving potassium‐ and magnesium‐losing agents, because of the risk of torsades de pointes. Ketanserin has potential utility in the treatment of eclampsia, peripheral vascular disease, carcinoid syndrome, and “shock lung.” The drug is not yet approved for clinical use in the United States.</jats:p>

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