Binding of dexetimide and levetimide to [3H](+)pentazocine- 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 [3H](+)pentazocine or [3H]1,3-di(2-tolyl)guanidine. Levetimide was a potent and stereoselective inhibitor of [3H](+)pentazocine binding, with a Ki of 2.2 nM, while dexetimide was nine-fold less potent (Ki = 19 nM). Dexetimide and levetimide potently inhibited [3H]DTG binding although without stereoselectivity (Ki values of 65 and 103 nM, respectively). Levetimide may be a useful tool with which to investigate sigma recognition sites and sigma subtypes.
DeHaven-Hudkins
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DL
Department of Enzymology and Receptor Biochemistry, Sterling Research Group, Malvern, PA 19355-1314.
Hudkins
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D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism; D003909:Dexetimide / Q000378:metabolism*; D006146:Guanidines / Q000378:metabolism; D006168:Guinea Pigs; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010423:Pentazocine / Q000378:metabolism; D011869:Radioligand Assay; D011976:Receptors, Muscarinic / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism*; D017480:Receptors, sigma
D006146:Guanidines; D011976:Receptors, Muscarinic; D011957:Receptors, Opioid; D017480:Receptors, sigma; C018580:levetimide; D003909:Dexetimide; C050232:1,3-ditolylguanidine; D010423:Pentazocine