Experimental Anticonvulsant Cinromide in Monkey Model: Preliminary Efficacy

Abstract

Cinromide (3 bromo-N-ethylcinnamamide), an experimental anticonvulsant was given a preliminary evaluation in an alumina-gel monkey model. The parent drug has a biological half-life in monkey of 1-2 h and its active metabolite, 3-bromocinnamide, a half-life of 4-6 h. In phase 1, 6 chronically epileptic monkeys, with focal motor and secondarily generalized tonic-clonic seizures, received the drug in a vehicle of 65% polyethylene glycol 400 (PEG) by constant-rate i.v. infusion followed by baseline days of saline only and PEG only. Different concentrations of cinromide (12, 24 and 36 mg/ml h) were administered, respectively, to achieve mean steady state plasma levels of .apprx. 5, 10 and 20 .mu.g/ml of the metabolie (0.5-5.0 .mu.g/ml of the parent drug). In phase 2, cinromide was administered for 7 days at the middle concentration to all monkeys. Baseline periods similar to those of phase 1 were used as controls. Apparently cinromide is effective in the monkey model at a plasma concentration range of 7-14 .mu.g/ml of the metabolites. With the exception of 1 animal, no secondarily generalized seizures were seen during drug administration (but were evident in the baseline periods) and EEG bursting decreased significantly in several monkeys. Minimal side effects were manifested at the plasma levels but withdrawal seizures were evinced with cessation of the drug. Further evaluation of cinromide by gastric administration in this animal model is planned.