Differential effects of agents enhancing purinergic transmission upon the antielectroshock efficacy of carbamazepine, diphenylhydantoin, diazepam, phenobarbital, and valproate in mice.
L-phenylisopropyladenosine (L-PIA; a preferential A1 adenosine agonist-0.05 mg/kg) offered no protection against electroconvulsions in mice but potentiated the anticonvulsant action of diazepam and valproate against maximal electroshock-induced seizures, decreasing the respective ED50 values from 9.5 to 4.0 mg/kg and from 250 to 185 mg/kg. However, it remained without effect on the protective activity of phenobarbital, carbamazepine and diphenylhydantoin. 5'-N-ethylcarboxamidoadenosine (NECA; a preferential A2 adenosine agonist-0.5 mg/kg) potentiated the efficacy of valproate. On the other hand, NECA (1 mg/kg) diminished the anticonvulsant action of phenobarbital (ED50 was elevated from 16.5 to 20.5 mg/kg), possessing no effect upon the protective action of carbamazepine. In addition, papaverine (20 mg/kg) significantly enhanced the protective efficacy of valproate and up to 40 mg/kg remained without influence upon the protective action of carbamazepine. However, papaverine (20 and 40 mg/kg) inhibited the anticonvulsive potential of phenobarbital. In the light of the results obtained A1 and A2 adenosine receptor-mediated events seem to possess different influences upon the protective effects of antiepileptic drugs.
Czuczwar
S J
SJ
Department of Pharmacology, Lublin Medical School, Poland.
Szczepanik
B
B
Wamil
A
A
Janusz
W
W
Kleinrok
Z
Z
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism / Q000627:therapeutic use*; D001833:Body Temperature Regulation / Q000187:drug effects; D003975:Diazepam / Q000627:therapeutic use*; D004597:Electroshock; D005260:Female; D051379:Mice; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D012640:Seizures / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D014635:Valproic Acid / Q000627:therapeutic use*
D000927:Anticonvulsants; D011983:Receptors, Purinergic; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D014635:Valproic Acid; D000241:Adenosine; D003975:Diazepam