This study set out to analyse the potential ability of some 5-hydroxytryptamine (5-HT) receptor ligands widely used in cardiovascular experimental models to interact with vascular α1-adrenoceptors in the pithed rat. These ligands included: methiothepin, methysergide and metergoline (5-HT1/5-HT2); WAY-100635, buspirone, ipsapirone and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (5-HT 1A); GR127935 (5-HT1B/1D); ketanserin, ritanserin, spiperone and pizotifen (5-HT2); granisetron and metoclopramide (5-HT3); tropisetron (5-HT3/5-HT4); ergotamine (5-HT1B/1D, 5-ht5A/5B); clozapine (5-HT 6/5-HT7); as well as LY215840 and mesulergine (5-HT 2/5-HT7). For this purpose, the increases in diastolic blood pressure produced by the selective α1-adrenoceptor agonist, phenylephrine, were analysed before and after the above antagonists or saline. The adrenoceptor antagonist properties of prazosin (α1) and yohimbine (α2) were also analysed for comparison. Thus, the phenylephrine-induced vasopressor responses were dose-dependently antagonised with the following apparent rank order of potency by: prazosin ≥ methiothepin > ketanserin > clozapine ≥ lisuride ≫ buspirone; this potency correlates with the affinity of these compounds for α1- adrenoceptor binding sites. In contrast, the other compounds were either devoid of any blocking effect on - or even potentiated (i.e. lisuride, methysergide, 8-OH-DPAT, granisetron and GR127935) - the responses to phenylephrine. These results show that methiothepin, ketanserin, clozapine, lisuride and buspirone can block α1-adrenoceptors in the rat systemic vasculature.

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European Journal of Pharmacology
Department of Pharmacology

Centurion, D., Mehotra, S., Sánchez-López, A., Gupta, S., Maassen van den Brink, A., & Villalón, C. (2006). Potential vascular α1-adrenoceptor blocking properties of an array of 5-HT receptor ligands in the rat. European Journal of Pharmacology, 535(1-3), 234–242. doi:10.1016/j.ejphar.2006.02.010