ISSN:
1432-1912
Keywords:
Key words 5-HT receptors
;
Arteriovenous anastomoses
;
Arteriovenous shunts
;
Carotid artery
;
Eletriptan
;
Migraine headache
;
Pig
;
Sumatriptan
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract It has been suggested that opening of cephalic arteriovenous anastomoses may be involved in the headache phase of migraine. Indeed, a number of acutely acting anti-migraine drugs, including the ergot alkaloids and sumatriptan, constrict porcine carotid arteriovenous anastomoses. In this study, using pentobarbital anaesthetised pigs, we investigated the effects of eletriptan, a close structural analogue of sumatriptan, on the distribution of common carotid artery blood flow into arteriovenous anastomotic and nutrient (capillary) fractions. Eletriptan (10, 30, 100, 300 and 1000 µg kg–1, i.v.) decreased the total carotid blood flow, exclusively by decreasing cephalic arteriovenous anastomotic blood flow; nutrient blood flow, particularly to the ear, skin and fat, was significantly increased. The doses of eletriptan needed to reduce arteriovenous anastomotic blood flow and conductance by 50% (ED 50) were, respectively, 117±21 µg kg–1 (251±45 nmol kg–1) and 184±42 µg kg–1 (396±91 nmol kg–1); the highest dose caused reductions of 84±3% and 77±4%, respectively. The eletriptan-induced changes in carotid haemodynamics were clearly attenuated by pretreating the pigs with the selective 5-HT1B/1D receptor antagonist GR127935 (0.5 mg kg–1). On the basis of these results, we conclude that (1) the eletriptan-induced constriction of cephalic arteriovenous anastomoses as well as the arteriolar dilatation in head tissues is predominantly mediated by 5-HT1B/1D receptors, and (2) eletriptan should be effective in aborting migraine headache. Clinical studies have already demonstrated its therapeutic action in migraine patients.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/PL00005245
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