Ergotamine Stimulates Human 5-HT4-Serotonin Receptors and Human H2-Histamine Receptors in the Heart

Ergotamine (2 '-methyl-5 'alpha-benzyl-12 '-hydroxy-3 ',6 ',18-trioxoergotaman) is a tryptamine-related alkaloid from the fungus Claviceps purpurea. Ergotamine is used to treat migraine. Ergotamine can bind to and activate several types of 5-HT1-serotonin receptors. Based on the structural formula of ergotamine, we hypothesized that ergotamine might stimulate 5-HT4-serotonin receptors or H-2-histamine receptors in the human heart. We observed that ergotamine exerted concentration- and time-dependent positive inotropic effects in isolated left atrial preparations in H-2-TG (mouse which exhibits cardiac-specific overexpression of the human H-2-histamine receptor). Similarly, ergotamine increased force of contraction in left atrial preparations from 5-HT4-TG (mouse which exhibits cardiac-specific overexpression of the human 5-HT4-serotonin receptor). An amount of 10 mu M ergotamine increased the left ventricular force of contraction in isolated retrogradely perfused spontaneously beating heart preparations of both 5-HT4-TG and H-2-TG. In the presence of the phosphodiesterase inhibitor cilostamide (1 mu M), ergotamine 10 mu M exerted positive inotropic effects in isolated electrically stimulated human right atrial preparations, obtained during cardiac surgery, that were attenuated by 10 mu M of the H-2-histamine receptor antagonist cimetidine, but not by 10 mu M of the 5-HT4-serotonin receptor antagonist tropisetron. These data suggest that ergotamine is in principle an agonist at human 5-HT4-serotonin receptors as well at human H-2-histamine receptors. Ergotamine acts as an agonist on H-2-histamine receptors in the human atrium.

Automated summary

Ergotamine is a tryptamine-related alkaloid used to treat migraines. It has positive inotropic effects on both 5-HT4-serotonin receptors and H-2-histamine receptors in the human heart.