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Pharmacological properties of JDTic: A novel kappa-opioid receptor antagonist

Biological studies were conducted on (3R)-7-Hydroxy-N-{(1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-pi peridinyl]methyl}-2-methylpropyl}-1,2,3,.4-tetrahydro-3-isoquinoline-car boxamide (JDTic), the first potent K-selective opioid receptor antagonist not derived from an opiate class of compounds. In the mouse tail-flick test, JDTic, administered subcutaneously (s.c.), blocked anticociceptive activity for up to 2 weeks. When JDTic was administered either s.c. or p.o. 24 h before the selective KOP (kappa)-opioid receptor agonist, enadoline, AD(50s) of 4.1 and 27.3, respectively, were obtained. A time-course study of JDTic versus enadoline indicated significant antagonist p.o. activity up to 28 days. In contrast, JDTic, s.c., failed to antagonize the analgesic effects of the selective MOP (mu)-opioid receptor agonist, sufentar. il. In the squirrel monkey shock titration antinociception test, JDTic given intramuscularly (i.m.) shifted the trans-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl] cyclohexyl) benzeneacetamide (U50,488) dose-effect curve to the right. In the U50,488-induced diuresis rat test, JDTic, s.c., suppressed diuretic activity with a greater potency than that of nor-binaltorphimine (nor-BNI). Thus, JDTic is a potent long- and orally acting selective kappa-opioid antagonist. (C) 2004 Elsevier B.V. All rights reserved


Carroll, F., Thomas, J., Dykstra, L. A., Granger, A., Allen, R. M., Howard, J. L., ... Harris, L. S. (2004). Pharmacological properties of JDTic: A novel kappa-opioid receptor antagonist. European Journal of Pharmacology, 501(1-3), 111-119. DOI: 10.1016/j.ejphar.2004.08.028