The effect of ergotamine and methysergide on serotonin metabolism in the rat brain.

Ergotamine tartrate and methysergide maleate each significantly altered serotonin (5-HT) metabolism in the rat brain. Whole brain levels of 5-HT were markedly reduced in a dose-related manner, with peak activity observed 30 minutes after I.P. administration and persisting through four hours after dosing. In addition, turnover rate of 5-HT was significantly increased. Pentylenetetrazol (PTZ)-induced convulsions were not inhibited by either ergotamine or methysergide but each drug interacted with PTZ to induce lethality, which is suggestive evidence of central 5-HT antagonist activity. Moreover, regional distribution of 5-HT in the rat brain was altered by these drugs in such a way to suggest that neihter was a "universally acting" central 5-HT antagonist.