Interactions between antimigraine drugs and a high affinity uptake and storage mechanism for 5-hydroxytryptamine

Rabbit hearts removed 3H-5-hydroxytryptamine (3H-5-HT) from a perfusion concentration of 2.6 X 10(-9) g/ml. 15.8% of the extractable cardiac total radioactivity consisted of metabolites, mainly 5-hydroxyindoleacetic acid, and metabolism appeared in the perfusion fluid during the course of the perfusion. Ergotamine tartrate (1.0 X 10(-6) g/ml) caused a small increase in 3H-5-HT uptake by the heart. Methysergide bimaleate (1.0 X 10(-6) g/ml) slowed the appearance of metabolites in the perfusion fluid. Because of the high concentrations required, neither observation seems likely to be of clinical significance to migraine. The results do, however, suggest that the frequently observed sensitisation of tissues to 5-HT by ergotamine and methysergide is not the result of inhibition of its tissue uptake.