CA2+ Modulators As Antidotes to Imipramine and Neurotransmitter Toxicity

Abstract

Flunarizine and nimodipine, Ca2+ modulators which exert antagonist effects against catecholamines and serotonin and have specific action on the brain, were used as antidotes to imipramine toxicity in the rat. Imipramine, a tricyclic antidepressant, inhibits synaptic reuptake of catecholamines and serotonin, Flunarizine administered concurrently with imipramine increased survival time significantly (p < 0.04). After a lethal dose of imipramine (85 mg/ kg) 5 out of 5 animals treated with flunarizine (2.37 ± 1.21 mg/kg in divided doses) and 4 out of 5 animals treated with nimodipine (0.36 ± 0.11 mg/kg) survived. The acute toxicity of imipramine might be related, in part, to drug-induced alteration in turnover of excitatory neurotransmitters which will induce intracellular Ca2+ accumulation and damage to vital organs. These toxic effects of endogenously produced neuroamines may be antagonized by nimodipine or flunarizine.