EFFECT OF CALCIUM-CHLORIDE AND 4-AMINOPYRIDINE THERAPY ON DESIPRAMINETOXICITY IN RATS

Background: Hypotension is a major contributor to mortality in tricycl ic antidepressant overdose. Recent data suggest that tricyclic antidep ressants inhibit calcium influx in some tissues. This study addressed the potential role of calcium channel blockade in tricyclic antidepres sant-induced hypotension. Methods: Two interventions were studied that have been shown previously to improve blood pressure with calcium cha nnel blocker overdose. CaCl2 and 4-aminopyridine. Anesthetized rats re ceived the tricyclic antidepressant desipramine IP to produce hypotens ion, QRS prolongation, and bradycardia. Fifteen min later, animals rec eived CaCl2, NaHCO3, or saline. In a second experiment, rats received tricyclic antidepressant desipramine IP followed in 15 min by 4-aminop yridine or saline. Results: NaHCO3 briefly (5 min) reversed hypotensio n and QRS prolongation. CaCl2 and 4-aminopyridine failed to improve bl ood pressure. The incidence of ventricular arrhythmias (p = 0.004) and seizures (p = 0.03) in the CaCl2 group was higher than the other grou ps. Conclusion: The administration of CaCl2 or 4-aminopyridine did not reverse tricyclic antidepressant-induced hypotension in rats. CaCl2 t herapy may possibly worsen both cardiovascular and central nervous sys tem toxicity. These findings do not support a role for calcium channel inhibition in the pathogenesis of tricyclic antidepressant-induced hy potension.