Anticonvulsant action of 1,3-dimethyl-5-aminoadamantane. Pharmacological studies in rodents and baboon, Papio papio

Abstract

The anticonvulsant actions of memantine (1,3-dimethyl-5-aminoadamantane) have been evaluated in mice (seizures induced by maximal electroshock, pentylenetetrazol, bicuculline, picrotoxin, 3-mercaptopropionic acid and N-methyl-D,L-aspartic acid) and in photosensitive baboons, Papio Papio (clonic responses to intermittent photic stimulation). Memantine, 5-20 mg/kg, raised the threshold for electroconvulsions and protected mice against the tonic hind limb extension in pentylenetetrazol-, bicuculline-, picrotoxin- and 3-mercaptopropionic acid-induced seizures, but was ineffective against the clonic phase of chemically-induced seizures. In the baboons, no protection against photomyoclonic responses was observed within 5 h after the intravenous administration of memantine, 1-9 mg/kg. Amantadine, 100 mg/kg, reduced the protective effect of memantine against electroconvulsions. Apomorphine, haloperidol, pimozide, spiroperidol and bicuculline did not modify the anticonvulsant activity of memantine in electroconvulsions. These studies demonstrate an anticonvulsant action of memantine in rodents and suggest that dopaminergic mechanisms do not contribute to its mechanism of action.