Abstract
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 GABAA antagonist bicuculline reversed the acute phase antinociception, whereas the GABAB 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.
Footnotes
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This study was supported by a gift from Abbott Diagnostics and in part by National Institute on Drug Abuse Grants R01-DA-11236 and R01-DA-01933 (to G.L.W.). National Institute on Drug Abuse Training Grant T32-DA-07097 supported T.M.L.
- Abbreviations:
- GBP
- gabapentin
- LTG
- lamotrigine
- TGB
- tiagabine
- DMSO
- dimethyl sulfoxide
- CI
- confidence interval
- Received December 18, 2001.
- Accepted May 6, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
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