The competitive NMDA antagonist, D-CPP-ene, potentiates the anticonvulsant activity of conventional antiepileptics against maximal electroshock-induced seizures in mice.
D-CPP-ene[3-(2-carboxy-piperazine-4-yl)-1-propenyl-1-phosphonic acid; a competitive antagonist of N-methyl-D-aspartic acid] in a dose of 2 mg/kg (i.p.) significantly increased the threshold for electroconvulsions. When given in a dose half that affecting the electroconvulsive threshold, D-CPP-ene potentiated the anticonvulsant activity of carbamazepine, diazepam, diphenylhydantoin, phenobarbital and valproate against maximal electroshock (50 mA)-induced seizures in mice. However, this NMDA antagonist did not influence the plasma levels of the antiepileptic drugs studied, so a pharmacokinetic interaction, in terms of total plasma levels at least, is not probable. The chimney test and retention test in mice revealed that the combined treatment of D-CPP-ene at 1.0 mg/kg (i.p.) with either diazepam, diphenylhydantoin, phenobarbital or valproate (providing a 50% protection against maximal electroshock convulsions) resulted in motor impairment and caused impairment of long-term memory. On the other hand, a combination of D-CPP-ene and carbamazepine was devoid of adverse effects. It can be concluded that the potential utility of D-CPP-ene in combination with conventional antiepileptic drugs does not seem promising, except for carbamazepine.
Zarnowski
T
T
Department of Pharmacology, Medical School, Lublin, Poland.
Kleinrok
Z
Z
Turski
W A
WA
Czuczwar
S J
SJ
D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D004357:Drug Synergism; D004597:Electroshock; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D010879:Piperazines / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000517:prevention & control*
D000927:Anticonvulsants; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; C065286:SDZ EAA 494