Biphasic effects of imipramine in experimental models of epilepsy.
In a variety of laboratory models of experimental epilepsy, imipramine exerts a biphasic action on the CNS as manifested by antiepileptic properties at low doses and convulsant effects at higher doses. In mice, imipramine (17.5-25 mg/kg, i.p.) blocks maximal electroshock seizures while exerting little or no effect on pentylenetetrazol-induced seizures. In cats, imipramine (2.5-15 mg/kg, i.v.) reduces penicillin and estrogen-induced epileptiform discharge, shortens afterdischarge duration and elevates afterdischarge threshold. Higher doses in mice induce neurotoxicity, including clonic seizures. In cats, doses above 20 mg/kg intensify chemically and electrically induced seizures and induce spontaneous epileptiform episodes. Such a biphasic action of imipramine may limit the drug's clinical utility as an antiepileptic agent and may provide an interesting tool for studies of catecholamines and brain excitability.
D000818:Animals; D002415:Cats; D002490:Central Nervous System / Q000187:drug effects; D004195:Disease Models, Animal; D004569:Electroencephalography; D004597:Electroshock; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology; D004966:Estrogens, Conjugated (USP); D005260:Female; D007099:Imipramine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D010406:Penicillins; D013997:Time Factors
D004966:Estrogens, Conjugated (USP); D010406:Penicillins; D007099:Imipramine