Comparison of antiepileptic drugs tiagabine, lamotrigine, and gabapentin in mouse models of acute, prolonged, and chronic nociception.
Some antiepileptic drugs have been shown to be clinically effective in the treatment of neuropathic pain. This study determined whether the new antiepileptic drug tiagabine, a GABA uptake inhibitor, is efficacious in mice in a broad range of nociceptive tests (hot-plate, formalin, and dynorphin-induced chronic allodynia) and compared tiagabine's potency with two other antiepileptic drugs, gabapentin and lamotrigine. Intraperitoneally administered tiagabine, but not lamotrigine, gabapentin, or i.t. tiagabine, produced dose-dependent antinoception in the hot-plate test. A 5-min pretreatment with tiagabine (2-29 nmol i.t.) dose-dependently inhibited both the acute and late phase formalin behaviors; pretreatment with lamotrigine (4-265 nmol i.t.) inhibited only the late phase. In the formalin assay the GABA(A) antagonist bicuculline reversed the acute phase antinociception, whereas the GABA(B) antagonist saclofen reversed both the acute and late phase tiagabine-induced antinociception. Tiagabine administered i.p. but not i.t. dose-dependently reduced dynorphin-induced chronic allodynia for 120 min. Gabapentin and lamotrigine produced antinociception administered either i.t. or i.p. in a dose-dependent manner. Thus, we have shown that gabapentin and lamotrigine produced antinociception in two mouse models of pain, whereas tiagabine produced antinociception in all three mouse models of pain.
Department of Pharmacology, Epilepsy Research and Education Program, College of Pharmacy, University of Minnesota, 7-170 WDH, 308 Harvard Street S.E., Minneapolis, MN 55455, USA.
Tinna M
TM
Laughlin
Kevin V
KV
Tram
George L
GL
Wilcox
Angela K
AK
Birnbaum
D000085:Acetates / Q000008:administration & dosage / Q000494:pharmacology*; D000208:Acute Disease; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000588:Amines; D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D002908:Chronic Disease; D003509:Cyclohexanecarboxylic Acids; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins; D005557:Formaldehyde; D018756:GABA Antagonists / Q000494:pharmacology; D000077206:Gabapentin; D006358:Hot Temperature; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D000077213:Lamotrigine; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009557:Nipecotic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D010147:Pain Measurement / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D000078308:Tiagabine; D014227:Triazines / Q000008:administration & dosage / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000316:Adrenergic alpha-Agonists; D000588:Amines; D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D018756:GABA Antagonists; D009557:Nipecotic Acids; D014227:Triazines; D005557:Formaldehyde; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D004399:Dynorphins; D000077213:Lamotrigine; D000078308:Tiagabine