Effects of JDTic, a selective kappa-opioid receptor antagonist, on the development and expression of physical dependence on morphine using a rat continuous-infusion model.
JDTic, (3R)-7-hydroxy-N-[(1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl]-2-methylpropyl]-1,2,3,4-tetrahydro-3-isoquinoline-carboxamide, is a potent and selective kappa-opioid antagonist with a very long duration of action [Carroll, F.I., Thomas, J.B., Dykstra, L.A., Granger, A.L., Allen, R.M., Howard, J.L., Pollard, G.T., Aceto, M.D., Harris, L.S., 2004. Pharmacological properties of JDTic: A novel k-opioid receptor antagonist. Eur. J. Pharmacol. 501, 111-119.]. When given 24 h prior to a continuous 4-day infusion of morphine sulfate in rats, JDTic did not prevent the stereotypy that developed during the infusion of morphine. It had no effect on the dramatic loss of body weight associated with the abrupt withdrawal of morphine. However, it decreased the number of important withdrawal signs designated wet-dog shakes and facial rubs. These data suggest that JDTic may find some application in the treatment of opiate abuse.
Carroll
F Ivy
FI
Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina, USA. fic@rti.org
Harris
Louis S
LS
Aceto
Mario D
MD
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D007260:Infusion Pumps; D007274:Injections, Intraperitoneal; D008297:Male; D023421:Models, Animal; D009020:Morphine / Q000008:administration & dosage / Q000633:toxicity; D009021:Morphine Dependence / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*; D013997:Time Factors
C433814:7-hydroxy-N-(1-((4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl)methyl)-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide; D010880:Piperidines; D017473:Receptors, Opioid, kappa; D044005:Tetrahydroisoquinolines; D009020:Morphine