Carotid vascular effects of ergotamine and dihydroergotamine in the pig: no exclusive mediation via 5-HT1-like receptors.
1. Though it is well known that the antimigraine drugs ergotamine and dihydroergotamine reduce carotid arteriovenous anastomotic shunting, it is uncertain whether a 5-HT1-like receptor is responsible for this effect. Using a high dose of methiothepin (3 mg kg-1), which completely blocks the carotid vascular effects of sumatriptan, we have attempted to study the role of 5-HT1-like receptors in the carotid vascular effects of ergotamine as well as dihydroergotamine in anaesthetized pigs. 2. Both ergotamine and dihydroergotamine increased arterial blood pressure and decreased heart rate. 3. The ergot alkaloids reduced dose-dependently total carotid blood flow and conductance as a result of a selective decrease in the arteriovenous anastomotic fraction. The nutrient fraction increased, particularly to bones, tongue and salivary glands with ergotamine and to ears, head skin, bones and salivary glands with dihydroergotamine. In contrast, dural vascular conductance tended to decrease. 4. Methiothepin (3 mg kg-1) partially antagonized the decrease in total carotid and arteriovenous anastomotic blood flow and conductance by the ergot alkaloids; the ED30 for ergotamine and dihydroergotamine (agonist dose eliciting a 30% decrease in arteriovenous anastomotic conductance) was raised by 3.1 and 5.2 fold respectively. 5. These results indicate that the effects of ergotamine and dihydroergotamine are partly mediated by methiothepin-sensitive receptors, which may probably belong to either 5-HT1-like or alpha 2-adrenoceptor category. However, an important part of the effect of ergot alkaloids is left after methiothepin and this could be mediated by other, perhaps novel, receptors.
den Boer
M O
MO
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands.
Heiligers
J P
JP
Saxena
P R
PR
D000818:Animals; D001163:Arteriovenous Anastomosis / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004087:Dihydroergotamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004878:Ergotamine / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007211:Indoles / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008719:Methiothepin / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D013449:Sulfonamides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018170:Sumatriptan; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D007211:Indoles; D011985:Receptors, Serotonin; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D004087:Dihydroergotamine; D008719:Methiothepin; D018170:Sumatriptan; D004878:Ergotamine