PMID: 41494Jul 1, 1979

Effects of clonidine, guanfacine and three imidazolidine derivatives related to clonidine on blood pressure, heart rate and gastric acid secretion in the anaesthetized rat

Archives Internationales De Pharmacodynamie Et De Thérapie
I C Medgett, M W McCulloch

Abstract

The effects of histamine, guanfacine, clonidine (2,6-dichlorophenylimino-2-imidazolidine) and the 2,6-dibromo, 2,3- and 2,5-dichloroanalogues of clonidine were assessed on blood pressure, heart rate and gastric acid secretion in the anaesthetized rat, with lumen-perfused stomach. Histamine (100 microgram/kg to 1 mg/kg) and clonidine (250 microgram/kg to 1 mg/kg) each caused acute increases in acid secretion, the magnitude and duration of which were dose-dependent: the secretory effect of clonidine was blocked by cimetidine (2 mg/kg). Histamine produced a short-lasting hypotension with no effect on heart rate, whereas clonidine produced an initial transient rise followed by a prolonged fall in blood pressure accompanied by a marked bradycardia. Guanfacine and the three clonidine analogues all produced cardiovascular effects similar to those of clonidine; however, only the 2,6-dibromo analogue increased gastric acid secretion. These results confirm previous findings using guinea-pig atria that only imidazolidine derivatives with 2,6-substitution in the phenyl ring activate histamine H2-receptors mediating gastric acid secretion in the rat; this is not so for the hypotensive and bradycardic effects of the compounds.

Related Concepts

Histamine Measurement
Gastric Juice
Derivatives
Entire Lumen of Body System
Phenyl
Bradycardia
Cavia
Diastolic Blood Pressure
Analog
Tagamet

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