Abstract
PD-217014, a new GABA analog (1α,3α,5α-3-aminomethyl-bicyclo[3.2.0]heptane-3-acetic acid), inhibited [<sup>3</sup>H]-gabapentin binding to α<sub>2</sub>δ subunit of voltage-gated calcium channels in a concentration-dependent manner (K<sub>i</sub> = 18 nmol/l). Oral treatment with PD-217014 significantly inhibited the visceral hypersensitivity induced by an intra-colonic injection of trinitrobenzene sulfonic acid in rats. The anti-hyperalgesic effect of PD-217014 increased in a dose-dependent manner, and reached a plateau level at 60 mg/kg p.o. The visceral analgesia produced by PD-217014 at 30 and 60 mg/kg p.o. correlated with blood concentrations within 4 h after dosing, and maximal efficacy was obtained 2 h after dosing when the maximal blood concentration was achieved at either dose. These results indicate that PD-217014 is a potent α<sub>2</sub>δ ligand and possesses visceral analgesic activity.
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