The antinociceptive effects of anticonvulsants in a mouse visceral pain model.
BACKGROUND
There is evidence supporting the antinociceptive effects of carbamazepine, oxcarbazepine, gabapentin, and topiramate in various models of neuropathic pain as well as inflammatory somatic pain. Data are lacking on the antinociceptive potential of these drugs against visceral pain. In this study, we examined and compared the effects of carbamazepine, oxcarbazepine, gabapentin, and topiramate in the writhing test as a visceral pain model in the mouse. In addition, the influence of these anticonvulsants on motor performance was examined to compare the tolerability of these anticonvulsants when used against acute visceral pain.


METHODS
The antinociceptive effects of these anticonvulsants were examined in the acetic acid writhing test in mice. The side effect propensity of these drugs was examined using the rotarod test.


RESULTS
Carbamazepine (25-60 mg/kg; p.o.), oxcarbazepine (10-40 mg/kg; p.o.), gabapentin (10-70 mg/kg; p.o.), and topiramate (5-30 mg/kg; p.o.) caused a significant dose-dependent reduction the number of writhes in the writhing test. In the rotarod test, carbamazepine (60-140 mg/kg; p.o.) and oxcarbazepine (120-450 mg/kg; p.o.) significantly reduced the time spent on the rotarod in a dose- and time-dependent manner. Gabapentin (1000-2000 mg/kg; p.o.) and topiramate (400-1500 mg/kg; p.o.) did not produce significant impairment of motor performance at the highest doses used. The therapeutic index (motor impairing dose TD(50)/writhing ED(50)) values were topiramate (>148.5) > gabapentin (>60.2) > oxcarbazepine (15.2) > carbamazepine (2.3).


CONCLUSIONS
These results indicate that oxcarbazepine, gabapentin, and topiramate are effective in the writhing model in mice, in a dose range, which is not related to motor impairment; topiramate is the most potent and the most tolerable drug.
Stepanovic-Petrovic
Radica M
RM
Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia. racabbr@eunet.yu
Tomic
Maja A
MA
Vuckovic
Sonja M
SM
Paranos
Sonja
S
Ugresic
Nenad D
ND
Prostran
Milica S
MS
Milovanovic
Slobodan
S
Boskovic
Bogdan
B
D019342:Acetic Acid; D000588:Amines / Q000494:pharmacology; D000700:Analgesics / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002220:Carbamazepine / Q000494:pharmacology; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000031:analogs & derivatives / Q000494:pharmacology; D000077206:Gabapentin; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D010147:Pain Measurement; D045442:Rotarod Performance Test; D013997:Time Factors; D000077236:Topiramate; D014781:Viscera / Q000294:innervation*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000588:Amines; D000700:Analgesics; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D000077236:Topiramate; D005632:Fructose; D002220:Carbamazepine; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D019342:Acetic Acid