Bupropion-induced convulsions: preclinical evaluation of antiepileptic drugs.
Bupropion, a unique, non-nicotine smoking cessation aid and an effective antidepressant, is well known to produce seizures following overdosing in humans. However, the experimental background for the usefulness of antiepileptic drugs in the protection against bupropion-induced convulsions has not been established yet. Therefore, we tested if the antiepileptic drugs were able to protect mice against clonic convulsions induced by intraperitoneally (i.p.) administered bupropion in the CD97 dose (139.5 mg/kg). Among 13 tested drugs, clonazepam showed the greatest potency (dose-dependent full protection; ED50 = 0.06 mg/kg, i.p.). No signs of locomotor impairment were observed in the rotarod test after anticonvulsive doses of clonazepam, resulting in a broad therapeutic window and favorable protective index (PI) (33.3). Gabapentin produced dose-dependent protection against convulsions at nontoxic doses (up to 1000 mg/kg), having PI>29. Diazepam in a very high dose showed full protection but its PI (1.7) was much less favorable than that of clonazepam. The PI values for ethosuximide, phenobarbital and valproate were slightly higher than unity and lower than 2, and for topiramate and felbamate were lower than unity. Phenytoin, carbamazepine, and lamotrigine as well as tiagabine failed to block the convulsant effects of bupropion even at doses that caused severe motor impairment. Our results encourage clinical testing of clonazepam against seizures developing after bupropion overdose.
Tutka
Piotr
P
Department of Pharmacology and Toxicology, Medical University of Lublin, Jaczewskiego 8, PL-20-090 Lublin, Poland. tutka@eskulap.am.lublin.pl
Mróz
Tomasz
T
Klucha
Katarzyna
K
Piekarczyk
Małgorzata
M
Wielosz
Marian
M
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D018687:Antidepressive Agents, Second-Generation; D001522:Behavior, Animal / Q000187:drug effects; D016642:Bupropion; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011897:Random Allocation; D045442:Rotarod Performance Test; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*
D000927:Anticonvulsants; D018687:Antidepressive Agents, Second-Generation; D016642:Bupropion