Cardiovascular and autonomic actions of ciclazindol and tricyclic antidepressants.
The novel antidepressant ciclazindol had no significant effect on blood pressure at doses of up to 25.6 mg/kg i.v. in anaesthetised rats. Desipramine, imipramine, nortriptyline and amitriptyline evoked significant decreases at 0.8-1.6 mg/kg. Ciclazindol had no sustained haemodynamic actions in anaesthetised cats apart from a small rise in dp/dt. The ECG waveform showed only minor voltage changes. Desipramine and nortriptyline elevated haemodynamic variables at low doses but decreases occurred at higher doses. Amitripyline and imipramine decreased blood pressure. ECG changes evoked by the tricyclics included QRS complex distortion, ventricular ectopic beats, nodal rhythm, bundle branch block and ventricular tachycardia. In skin wheal tests ciclazindol was equiactive with the tricyclics as a local anaesthetic. In isolated tissues ciclazindol was not anticholinergic, showed no marked antagonism of 5-HT, potentiated responses to noradrenaline and was weakly antihistaminic. Ciclazindol appears to be pharmacologically different from the tricyclics and may not produce the unwanted side effects associated with these compounds.
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001341:Autonomic Nervous System / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004562:Electrocardiography; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D012882:Skin Tests; D013045:Species Specificity; D014661:Vasoconstriction / Q000187:drug effects
D000929:Antidepressive Agents, Tricyclic; D007211:Indoles; D011743:Pyrimidines; C009990:ciclazindol