Effects of S9977 and dihydroergotamine in an animal experimental model for migraine

• Published in: Pharmacological research 1992-02, Vol.25 (2), p.125-137
• Main Authors: Villalon, Carlos M., Bom, Anton H., Den Boer, Marinus O., Heiligers, Jan P.C., Saxena, Pramod R.
• Format: Article
• Language: English
• Subjects: Animals; arteriovenous anastomoses; Biological and medical sciences; Cardiovascular system; Carotid Arteries - drug effects; dihydroergotamine; Dihydroergotamine - pharmacology; Dihydroergotamine - therapeutic use; Disease Models, Animal; Hemodynamics - drug effects; Infusions, Intravenous; Medical sciences; migraine; Migraine Disorders - drug therapy; Pharmacology. Drug treatments; Piperazines - pharmacology; Piperazines - therapeutic use; S9977; Swine; Vasodilator agents. Cerebral vasodilators; Xanthines - pharmacology; Xanthines - therapeutic use
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/1043-6618(92)91381-P

The present study concerns the effects of S9977, a trimethylxanthine derivative with potential antimigraine characteristics, on the distribution of carotid blood flow in the anaesthetized pig. Furthermore, the effects of dihydroergotamine have been analysed for comparison. Dihydroergotamine (3, 10, 30 and 100 μg/kg, i.v.) elicited dose-dependent pressor and bradycardiac responses which were probably mediated by its partial agonist action on α-adrenoceptors and dopamine 2 receptors. In contrast, S9977 (0.3, 1, 3 and 10 mg/kg, i.v.) caused a moderate hypotension and bradycardia. The carotid haemodynamic effects of dihydroergotamine (3, 10, 30 and 100 μg/kg, i.v.) consisted of a dose-dependent reduction of arteriovenous anastomotic blood flow and conductance and an increase in nutrient (tissue) blood flow and conductance. As a consequence, jugular venous Po 2 decreased. These findings, demonstrating an active constriction of arteriovenous anastomoses, are in agreement with earlier findings in cats. Though S9977 (0.3, 1, 3 and 10 mg/kg i.v.) decreased carotid (two highest doses) and arteriovenous anastomotic (highest dose) blood flow, there was no concomitant decrease in the vascular conductances. Therefore, the effects of S9977 seem to be related to a decrease in arterial blood pressure and not to an active vasoconstriction of arteriovenous anastomoses. These results are discussed in terms of the potential therapeutical usefulness of S9977 in the treatment of migraine.