Brain cyclic nucleotides and the development of convulsion, with reference to the anticonvulsant activity of diazepam.

Dibutyryl cyclic GMP (DbcGMP) or dibutyryl cyclic AMP (DbcAMP) given to mice intracerebroventricularly in a dose of 200 or 400 nmol/head produced electroencephalographic and electromyographic changes corresponding to twitches, and clonic and tonic convulsions. Lower doses of DbcGMP or DbcAMP facilitated the pentylenetetrazol-induced clonic and tonic convulsions. Diazepam given intraperitoneally in a dose of 0.5 mg/kg suppressed clonic and tonic convulsions induced by DbcGMP and DbcAMP, but the twitches were not suppressed. These results suggest that these nucleotides lower the threshold for electrical discharges related to convulsion and facilitate the propagation of convulsion. Diazepam suppresses this facilitation.