Influence of orphenadrine upon the protective activity of various antiepileptics in the maximal electroshock-induced convulsions in mice.
Orphenadrine is an anticholinergic drug used in the treatment of Parkinson's disease, and is also known to exert nonspecific antagonistic activity at the phencyclidine binding site of the N-methyl-D-aspartate (NMDA) receptor. The aim of this study was to assess the anticonvulsant properties of orphenadrine and to evaluate its effect on the anticonvulsant activity of antiepileptic drugs against maximal electroshock-induced seizures in mice. Orphenadrine given at a dose of 5.65 mg/kg elevated the electrical seizure threshold from 5.7 (5.4-6.1) to 6.8 (6.3-7.3) mA, while a dose of 2.8 mg/kg was ineffective. The ED(50) values of orphenadrine administered 10, 30 and 120 min before maximal electroshock-induced convulsions were 16.8 (11.3-25.1), 17.8 (15.7-20.0) and 25.6 (23.3-28.3) mg/kg, respectively. Orphenadrine at a sub-threshold dose of 2.8 mg/kg significantly enhanced the anticonvulsant activity of valproate by reducing its ED(50) value from 315.8 (270.0-369.4) to 245.9 (207.1-292.0) mg/kg without affecting the free plasma levels of valproate. However, orphenadrine failed to enhance the protective activity of carbamazepine, phenytoin, phenobarbital, lamotrigine, topiramate, or oxcarbazepine against maximal electroshock-induced seizures.
Czuczwar
Mirosław
M
2nd Department of Anesthesiology and Intensive Care, Medical University, Staszica 16, PL 20-081 Lublin, Poland. mireck@interia.pl
Cieszczyk
Jacek
J
Czuczwar
Katarzyna
K
Kiś
Jacek
J
Saran
Tomasz
T
Turski
Waldemar A
WA
D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000627:therapeutic use*; D004357:Drug Synergism; D004597:Electroshock / Q000379:methods; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000097:blood / Q000627:therapeutic use*; D009966:Orphenadrine / Q000097:blood / Q000627:therapeutic use*; D011897:Random Allocation; D012640:Seizures / Q000097:blood / Q000517:prevention & control*
D000927:Anticonvulsants; D018696:Neuroprotective Agents; D009966:Orphenadrine