LOSS OF SELECTIVITY OF SO-CALLED SELECTIVE ALPHA-1-ADRENOCEPTOR AGONISTS AFTER PHENOXYBENZAMINE

• Type: Article in International Scientific Journal
• Date: 1988

Authors

GONCALVES, J (Author) FFUP; NUNES, JP (Author) FMUP; PAIVA, MQ (Author) Other; GUIMARAES, S (Author) Other

Journal

Title: Naunyn-Schmiedeberg's Archives of Pharmacology

Vol. 338

Pages: 234-238

ISSN: 0028-1298

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 3 Citations

Scopus - 3 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-001-T88

Abstract (EN): This study examined the nature of ¿-adrenoceptor subtype involved in pressor responses to so-called selective ¿1-adrenoceptor agonists after treatment with phenoxybenzamine in vivo. The influence of prazosin (0.1 mg/kg) and of yohimbine (1 mg/kg) on the dose-response curves for cirazoline in the pithed rat, and for phenylephrine in the anaesthetized dog were compared, after various doses of phenoxybenzamine. In the pithed rat, after 0.05 mg/kg phenoxybenzamine, prazosin caused about equal displacements; after 1 mg/kg phenosybenzamine, yohimbine caused a displacement of the dose-response curve of cirazoline to the right which was much larger than that caused by yohimbine; after 0.3 mg/kg phenoxybenzamine, prazosin and yohimbine caused a marked displacement, while prazosin was without effect. In the anaesthetized dog, after 1 mg/kg phenoxybenzamine, prazosin and yohimbine produced about equal rightward shifts of the dose-response curve for phenylephrine. However, after 3 mg/kg phenoxybenzamine the rightward shift of the dose response curve for phenylephrine was much larger after yohimbine than after prazosin. In the anaesthetized dog, verapamil (1 mg/kg) caused a small and parallel rigtward shift of the dose-response curve for phenylephrine before phenoxybenzamine and a large and non-parallel one after phenoxybenzamine (3 mg/kg); the effect of verapamil on responses to the selective ¿2-adrenoceptor agonist UK-14,304 (before and after phenoxybenzamine) were similar to those on responses to phenylephrine after phenoxybenzamine. It is concluded that after 1 mg/kg phenoxybenzamine in the pithed rat or after 3 mg/kg phenoxybenzamine in the anaesthetized dog, the responses to the so-called selective ¿1-adrenoceptor agonists cirazoline and phenylephrine, respectively, are predominantly or totally ¿2-adrenoceptor-mediated. This explains why after inactivation of ¿1-adrenoceptors by phenoxybenzamine, the so-called selective ¿1- and ¿2-adrenoceptor agonists are equally antagonized by calcium entry blockers.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 5