Serotonin and serotonin antagonism in cardiovascular and non-cardiovascular disease

J Clin Pharmacol. 1995 Jun;35(6):541-72. doi: 10.1002/j.1552-4604.1995.tb05013.x.

Abstract

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 S1 receptor mediates vasodilation, and the S2 receptor vasoconstriction). Serotonin via the S2 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 S2-serotonergic antagonist with additional alpha-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.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / physiopathology
  • Cardiovascular System / drug effects
  • Clinical Trials as Topic
  • Coronary Disease / drug therapy
  • Heart Failure / drug therapy
  • Heart Valve Diseases / drug therapy
  • Humans
  • Hypertension / drug therapy
  • Hypertension / etiology
  • Ketanserin / pharmacology*
  • Ketanserin / therapeutic use
  • Peripheral Vascular Diseases / drug therapy
  • Receptors, Serotonin / metabolism
  • Serotonin / pharmacology*
  • Serotonin / physiology
  • Serotonin Antagonists / therapeutic use

Substances

  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin
  • Ketanserin