Binding of dexetimide and levetimide to [3H](+)pentazocine- and [3H]1,3-Dl(2-tolyl)guanidine-defined σ recognition sites

The potent antimuscarinic benzetimide and its resolved stereoisomers dexetimide and levetimide were tested for their affinities at σ sites labelled by [ 3 H](+)pentazocine or [ 3 H]1,3-di(2-tolyl)guanidine. Levetimide was a potent and stereoselective inhibitor of [ 3 H](+)pentazocine binding, with a K i of 2.2 nM, while dexetimide was nine-fold less potent (K i = 19 nM). Dexetimide and levetimide potently inhibited [ 3 H]DTG binding although without stereoselectivity (K i values of 65 and 103 nM, respectively). Levetimide may be a useful tool with which to investigate σ recognition sites and σ subtypes.