Central effects of the potent and highly selective mu opioid antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) in mice.
The ability of the selective cyclic mu-opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), to inhibit the acute and chronic effects of morphine in vivo was studied in mice. Intracerebroventricular (i.c.v.) administration of CTOP antagonized the analgesic effect of morphine in a dose-dependent manner, as measured by the heat-irradiant (tail-flick) method. CTOP was more effective than naloxone in inhibiting analgesia on a molar basis. CTOP also antagonized the acute morphine-induced hypermotility. CTOP caused withdrawal hypothermia and a loss of body weight in morphine-dependent animals. After the development of morphine-induced chronic dependence, CTOP administered i.c.v. caused a dose-dependent loss of body weight and hypothermia, and was about 10-400 times more potent than naloxone. CTOP administered alone to drugnaive mice did not cause antinociception, changes in body weight or body temperature.
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D004361:Drug Tolerance; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology; D009021:Morphine Dependence / Q000523:psychology; D009043:Motor Activity / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects; D010146:Pain / Q000503:physiopathology; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000378:metabolism*; D017450:Receptors, Opioid, mu; D012684:Sensory Thresholds / Q000187:drug effects; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology
D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D013004:Somatostatin; D009020:Morphine