Effects of ergotamine and dihydroergotamine on 5-hydroxytryptamine-2A receptors in the isolated rat aorta.
Ergotamine contracted isolated rat aorta rings with an intrinsic activity of 50% of that of 5-hydroxytryptamine. (5-HT, 0.1 mmol/l). Dihydroergotamine did not contract the tissue, but insurmountably blocked contraction in response to ergotamine and 5-HT. The 5-HT2A receptor antagonist, ketanserin (0.1 mumol/l), inhibited ergotamine (pKB 8.0) and 5-HT (pKB 8.1) induced contractions. These results indicate that in the rat aorta ergotamine is a partial 5-HT2A receptor agonist, whilst dihydroergotamine is an insurmountable 5-HT2A receptor antagonist. The present data could explain why ergotamine displays more cardiovascular and uterotonic side effects than dihydroergotamine.
Kalkman
H O
HO
Preclinical Research, Sandoz Pharma Ltd., Basel, Switzerland.
Schneider
F
F
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D004087:Dihydroergotamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004878:Ergotamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D014662:Vasoconstrictor Agents; D012701:Serotonin; D004087:Dihydroergotamine; D004878:Ergotamine