title: 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 less than 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.
mesh_terms: D000818:Animals; D000931:Antidotes; D002118:Calcium / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000517:prevention & control; D005444:Flunarizine / Q000627:therapeutic use*; D007099:Imipramine / Q000633:toxicity*; D008297:Male; D018377:Neurotransmitter Agents / Q000633:toxicity*; D009553:Nimodipine / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000931:Antidotes; D018377:Neurotransmitter Agents; D009553:Nimodipine; D007099:Imipramine; D005444:Flunarizine; D002118:Calcium