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Relationship between plasma and brain concentrations of Denzimol and its anticonvulsant and neurotoxic effects in the rat.

The relationship between plasma, brain and cerebellum concentrations of Denzimol a new anticonvulsant agent, and its anticonvulsant and neurotoxic effects were studied in the rat. Sixty minutes after oral administration, a high brain/plasma concentration ratio of 10:1 was found. Mean plasma, brain and cerebellum half-lives of the drug were 8.4, 7.1 and 9.2 hr, respectively. The anticonvulsant activity of the drug was examined by maximal electroshok seizures (MES). Neurotoxicity was determined both by the rotarod performance test and by behavioural observation. Denzimol was effective against MES, in the ranges of 0.8-5 micrograms/ml and 10-50 micrograms/ml for plasma and brain concentrations, respectively, without causing clear signs of neurological toxicity. It is concluded that the anticonvulsant and neurotoxic effects of denzimol are correlated to its plasma and brain concentrations.