A comparative study on hypotensive and bradycardic effects of some new imidazole derivatives with possible central mechanism of action.
Cardiovascular actions of 4(5)-(2,6-dimethylbenzyl)imidazole (MPV-207) and its three alkyl bridge analogues were investigated in urethane-anaesthetized normotensive rats. Intravenous (i.v.) injections of 0.001-0.1 mg/kg of MPV-207 lowered mean arterial pressure (MAP) and heart rate (HR) in a dose-dependent manner. The compound was effective also upon intracerebroventricular (i.c.v.) administration. The hypotensive effect of i.v. injected MPV-207 (5 micrograms/kg) was attenuated by i.c.v. administered yohimbine (100 micrograms/kg), an alpha 2-adrenoceptor antagonist. MPV-295 having an ethano group between the phenyl and imidazole moieties decreased MAP and HR at i.v. doses of 0.03-3 mg/kg, being active also after i.c.v. injection. Extension of the alkyl bridge to the propano group further decreased the hypotensive and bradycardic activity, and the compound having a butano bridge was practically inactive. The results indicate that the extension of the alkyl bridge between the phenyl and imidazole rings reduces the hypotensive and bradycardic activities of the MPV compounds. Furthermore, the hypotensive action of these compounds may be mediated by a central mechanism involving a stimulation of alpha-adrenoceptors.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D015016:Yohimbine / Q000494:pharmacology
D007093:Imidazoles; D015016:Yohimbine; C037818:4(5)-(2,6-dimethylbenzyl)imidazole