5′-Guanidinonaltrindole, a highly selective and potent κ-opioid receptor antagonist

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 κ-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.