Comparison of the effects of anticonvulsant drugs with diverse mechanisms of action in the formalin test in rats.
The purpose of the present studies was to compare anticonvulsant drugs with diverse mechanisms of action in a persistent pain model, the formalin test. In addition, the anticonvulsant effects of the compounds were determined in the threshold electroshock tonic seizure test and the 6-Hz limbic seizure test. The effects of the compounds were also determined on locomotor activity. Carbamazepine, oxcarbazepine, lamotrigine, gabapentin and ethosuximide all produced statistically significant analgesic effects in the formalin test whereas phenytoin, topiramate, zonisamide, phenobarbital, tiagabine, valproate and levetiracetam did not. All compounds were anticonvulsant. In addition, morphine and phenobarbital increased locomotor activity while ethosuximide had no effect and all other compounds decreased locomotor activity. For those compounds that were analgesic, the doses required to produce analgesia were larger in magnitude than the anticonvulsant ED50 values in the threshold electroshock and 6-Hz tests, as well as larger than doses that altered locomotor activity. The present results demonstrate that the anticonvulsant and analgesic effects of clinically used antiepileptic drugs do not necessarily correlate and therefore suggest that the anticonvulsant and analgesic efficacy of these drugs may be due to different pharmacologic mechanisms.
Shannon
Harlan E
HE
Neuroscience Division, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. h.shannon@lilly.com
Eberle
Elizabeth Lutz
EL
Peters
Steven C
SC
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000517:prevention & control; D026941:Sodium Channel Blockers / Q000494:pharmacology
D000701:Analgesics, Opioid; D000927:Anticonvulsants; D018756:GABA Antagonists; D026941:Sodium Channel Blockers