BINDING OF DEXETIMIDE AND LEVETIMIDE TO [3H](+)PENTAZOCINE-DEFINED AND [3H]1,3-DI(2-TOLYL)GUANIDINE-DEFINED SIGMA-RECOGNITION SITES

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