Potential vascular alpha1-adrenoceptor blocking properties of an array of 5-HT receptor ligands in the rat.
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 alpha1-adrenoceptors in the pithed rat. These ligands included: methiothepin, methysergide and metergoline (5-HT(1)/5-HT2); WAY-100635, buspirone, ipsapirone and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (5-HT(1A)); GR127935 (5-HT(1B/1D)); ketanserin, ritanserin, spiperone and pizotifen (5-HT2); granisetron and metoclopramide (5-HT3); tropisetron (5-HT3/5-HT4); ergotamine (5-HT(1B/1D), 5-ht(5A/5B)); clozapine (5-HT6/5-HT7); as well as LY215840 and mesulergine (5-HT2/5-HT7). For this purpose, the increases in diastolic blood pressure produced by the selective alpha1-adrenoceptor agonist, phenylephrine, were analysed before and after the above antagonists or saline. The adrenoceptor antagonist properties of prazosin (alpha1) and yohimbine (alpha2) 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 > or = methiothepin > ketanserin > clozapine > or = lisuride >> buspirone; this potency correlates with the affinity of these compounds for alpha1-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 alpha1-adrenoceptors in the rat systemic vasculature.
Departamento de Farmacobiología, Cinvestav-Coapa., Czda. de los Tenorios 235, Col. Granjas-Coapa, 14330 México D.F., México.
David
D
Centurión
Suneet
S
Mehotra
Araceli
A
Sánchez-López
Saurabh
S
Gupta
Antoinette
A
MaassenVanDenBrink
Carlos M
CM
Villalón
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002065:Buspirone / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004878:Ergotamine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D007650:Ketanserin / Q000494:pharmacology; D008090:Lisuride / Q000494:pharmacology; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D008719:Methiothepin / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010918:Pizotyline / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D011725:Pyridines; D018340:Receptors, Adrenergic, alpha-1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D010918:Pizotyline; D008711:Metergoline; D010656:Phenylephrine; D015016:Yohimbine; D008719:Methiothepin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; D008090:Lisuride; D003024:Clozapine; D004878:Ergotamine; D002065:Buspirone; D011224:Prazosin; D008784:Methysergide