Influence of D-cycloserine on the anticonvulsant activity of some antiepileptic drugs against audiogenic seizures in DBA/2 mice

D-Cycloserine (DCS: 1-100 mg/kg, intraperitoneally (i.p.)) was able to anta gonise the audiogenic seizures in DBA/2 mice in a dose-dependent manner. DC S, 2.5 mg/kg i.p, did not significantly affect the occurrence of audiogenic seizures in DBA/2 mice, but potentiated the anticonvulsant activity of car bamazepine. diazepam, felbamate, lamotrigine, phenytoin, phenobarbital and valproate against sound-induced seizures in DBA/2 mice. The degree of poten tiation induced by DCS was greatest for diazepam, phenobarbital, phenytoin and valproate, less for carbamazepine and least for lamotrigine and felbama te. The increase in anticonvulsant activity was usually associated with a c omparable increase in motor impairment. However, the therapeutic index of t he combined treatment of the above drugs + DCS, was more favourable than th e same drugs + saline with the exception of DCS + carbamazepine and DCS + l amotrigine. Since DCS did not significantly influence the total and free pl asma levels of the anticonvulsant drugs studied, pharmacokinetic interactio ns, in terms of plasma levels, are not probable. The possibility that DCS c an modify the clearance fi om the brain of the anticonvulsant drugs studied cannot be excluded. DCS did not significantly affect the hypothermic effec ts of the anticonvulsants tested. In conclusion, DCS potentiates the antico nvulsant action of some classical antiepileptic drugs, most notably diazepa m, phenobarbital, phenytoin and valproate. (C) 2000 Elsevier Science B.V. A ll rights reserved.