Serotonergic type-2 (5-HT2) antagonists: a novel class of cardiovascular drugs

Serotonin (5-hydroxytryptamine; 5-HT) is widely distributed in the body and subserves many functions. Tissue specificity of action is aided by differential receptor structure and function; the type 2 (5-HT2) receptor mediates arterial constriction and platelet aggregation. Very little serotonin is free in plasma, most being platelet-bound; however, local platelet activation and consequent serotonin release can present free serotonin to peripheral tissues. Serotonin, acting via the 5-HT2 receptor, can contribute to a range of cardiovascular problems, including portal hypertension, Raynaud's phenomenon, carcinoid flushes, preeclampsia, hypertension, arterial atheroma, and restenosis after angioplasty or thrombolysis. 5-HT2 antagonists have a potential therapeutic role in all these conditions. The diversity of such syndromes requires that the term "vascular protection" should not be applied loosely, but must always be precisely defined. Future 5-HT2 antagonists will probably be of two kinds: (a) with weak accompanying alpha 1 antagonism where blood pressure reduction is needed; and (b) as "pure" 5-HT2 antagonists, for use where arterial pressure falls are best avoided.