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 antagonise the audiogenic seizures in DBA/2 mice in a dose-dependent manner. DCS, 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 carbamazepine, diazepam, felbamate, lamotrigine, phenytoin, phenobarbital and valproate against sound-induced seizures in DBA/2 mice. The degree of potentiation induced by DCS was greatest for diazepam, phenobarbital, phenytoin and valproate, less for carbamazepine and least for lamotrigine and felbamate. The increase in anticonvulsant activity was usually associated with a comparable increase in motor impairment. However, the therapeutic index of the combined treatment of the above drugs+DCS, was more favourable than the same drugs+saline with the exception of DCS+carbamazepine and DCS+lamotrigine. Since DCS did not significantly influence the total and free plasma levels of the anticonvulsant drugs studied, pharmacokinetic interactions, in terms of plasma levels, are not probable. The possibility that DCS can modify the clearance from the brain of the anticonvulsant drugs studied cannot be excluded. DCS did not significantly affect the hypothermic effects of the anticonvulsants tested. In conclusion, DCS potentiates the anticonvulsant action of some classical antiepileptic drugs, most notably diazepam, phenobarbital, phenytoin and valproate.
De Sarro
G
G
Department of Experimental and Clinical Medicine, Faculty of Medicine and Surgery, University of Catanzaro, Policlinico Mater Domini, Via T. Campanella 115, 88100, Catanzaro, Italy. desarro@unicz.it
Gratteri
S
S
Naccari
F
F
Pasculli
M P
MP
De Sarro
A
A
D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000494:pharmacology*; D000963:Antimetabolites / Q000097:blood / Q000494:pharmacology*; D003523:Cycloserine / Q000097:blood / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D020195:Epilepsy, Reflex / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009043:Motor Activity / Q000187:drug effects*
D000927:Anticonvulsants; D000963:Antimetabolites; D003523:Cycloserine