Pathophysiological and pharmacotherapeutic aspects of serotonin and serotonergic drugs

A survey shall be given on the physiological, pathophysiological and pharmacotherapeutic backgrounds of the biogenic amine 5-hydroxytryptamine (serotonin; 5HT), to be preceded by a few historical remarks. 5HT is biosynthesized from L-tryptophan via hydroxylation and subsequent decarboxylation. 5HT is predominantly found in enterochromaffin cells, platelets and in various structures of the central nervous system. Its concentration in circulating blood is low and probably subthreshold. Whereas the physiological role of 5HT is rather unclear, 5HT appears to play a relevant role in certain psychiatric disorders, in migraine and the carcinoid syndrome. Its role in essential hypertension remains uncertain. However, 5HT appears to contribute to and to exacerbate the damage to blood vessels which were already predamaged by atherosclerosis, diabetes mellitus or possibly old age as such. A major breakthrough in the pharmacology of the serotonergic system was achieved by the discovery of several subtypes of 5HT receptors, with a corresponding collection of selective agonists and antagonists towards these receptor subtypes. This development is the basis of various drugs which interact with the serotonergic system and its receptors, like the various 5HT2 receptor antagonists (of which ketanserin is the prototype), methysergide, pizotifen, urapidil, flesinoxan and a variety of psychoactive drugs. The most important of these drugs and their potential application will be discussed with an emphasis on cardiovascular disorders.