title: Tolerance to analgesia and dependence liability by topical application of dihydroetorphine to hairless rats.
abstract: The tolerance to analgesia and dependence liability of dihydroetorphine following topical application were investigated in hairless rats with and without formalin-induced inflammation. The analgesic effect of dihydroetorphine (s.c.) was 4600- to 7200-fold more potent than that of morphine. In non-inflamed rats, the analgesic effect of 24-h topical application of dihydroetorphine tape (35 microg) and 4-day repeated tape applications (20 microg/5 h/day) decreased with time after the start of application, even though the plasma dihydroetorphine concentrations did not decrease. In formalin-inflamed rats, however, the tolerance to analgesia diminished. Naloxone-precipitated weight loss was observed after 24-h infusion of dihydroetorphine but not after the tape application in non-inflamed rats. A significant rewarding effect was found in the non-inflamed rats conditioned by s.c. injection and tape application but not in the formalin-inflamed rats. These results indicate that topical application of dihydroetorphine has a tolerance and dependence liability when there is no pain, and therefore, it should be used only for pain relief.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ohmori
authors.forename: L
authors.initials: L
authors.lastname: Fang
authors.forename: M
authors.initials: M
authors.lastname: Kawase
authors.forename: S
authors.initials: S
authors.lastname: Saito
authors.forename: Y
authors.initials: Y
authors.lastname: Morimoto
mesh_terms: D000279:Administration, Cutaneous; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005048:Etorphine / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology*; D005557:Formaldehyde; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D011923:Rats, Nude; D019966:Substance-Related Disorders; D013997:Time Factors; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D005557:Formaldehyde; D009270:Naloxone; D005048:Etorphine; D009020:Morphine; C034765:18,19-dihydroetorphine