CARDIOVASCULAR AND AUTONOMIC ACTIONS OF CICLAZINDOL AND TRICYCLIC ANTI-DEPRESSANTS

  • 1 January 1979
    • journal article
    • research article
    • Vol. 240  (1) , 116-136
Abstract
The novel antidepressant ciclazindol had no significant effect on blood pressure at doses of up to 25.6 mg/kg i.v. in anesthetized rats. Desipramine, imipramine, nortriptyline and amitriptyline evoked significant decreases at 0.8-1.6 mg/kg. Ciclazindol had no sustained hemodynamic actions in anesthetized cats apart from a small rise in dp/dt [the 1st derivative of left ventricular pressure]. The ECG waveform showed only minor voltage changes. Desipramine and nortriptyline elevated hemodynamic variables at low doses but decreases occurred at higher doses. Amitriptyline 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 [guinea pig] wheal tests, ciclazindol was equiactive with the tricyclics as a local anesthetic. In isolated tissues [guinea pig atria and ileum, rat ileum and perfused mesenteric vasculature] ciclazindol was not anticholinergic, showed no marked antagonism of 5-HT [hydroxytryptamine], potentiated responses to noradrenaline [norepinephrine] 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.