Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, 308 Harvard Street S.E., Minneapolis, MN 55455, USA.
5'-Guanidinonaltrindole (GNTI) possesses 5-fold greater opioid antagonist potency (K(e)=0.04 nM) and an order of magnitude greater selectivity (selectivity ratios >500) than the prototypical kappa-opioid receptor antagonist, norbinaltorphimine, in smooth muscle preparations. Binding and functional studies conducted on cloned human opioid receptors expressed in Chinese hamster ovarian (CHO) cells afforded pA(2) values that were comparable to the smooth muscle data. In view of the high selectivity and potency of GNTI, it is a potentially valuable pharmacological tool for opioid research.