title: Effects of clonidine, guanfacine and three imidazolidine derivatives related to clonidine on blood pressure, heart rate and gastric acid secretion in the anaesthetized rat.
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.
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002927:Cimetidine / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology*; D005260:Female; D005750:Gastric Juice / Q000187:drug effects / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D010648:Phenylacetates / Q000494:pharmacology*; D051381:Rats
chemical_list: D000959:Antihypertensive Agents; D006146:Guanidines; D007093:Imidazoles; D010648:Phenylacetates; D002927:Cimetidine; D006632:Histamine; D003000:Clonidine