Cardiovascular and anticholinergic effects of zimelidine

1. Pentobarbital anaesthetized mongrel dogs on artificial respiration were instrumented for recording of cardiovascular parameters. 2. Zimelidine or tricyclic antidepressants (amitriptyline, clomipramine or desipramine) were given i.v. at a rate of 0.5 mg/kg/min. 3. Zimelidine caused a moderate decrease in mean arterial blood pressure and in peripheral resistance. These effects were not dose dependent. 4. The tricyclic antidepressants induced a dose dependent decrease in mean arterial blood pressure and dose dependent increases in left ventricular enddiastolic pressure and in right atrial pressure. 5. It is concluded that the tricyclics have direct effects on the heart. Zimelidine has negligible direct heart effects but decreases peripheral resistance. 6. Studies in rat brain homogenates indicated very low affinity of zimelidine to muscarinic receptors. 7. Studies in mice indicated no central or peripheral anticholinergic effects of zimelidine in contrast to the tricyclics.