title: A preclinical comparison between different opioids: antinociceptive versus adverse effects.
abstract: Reduced side-effect liability of opioids may enhance the patient's quality of life and decrease the incidence of opioid-insensitive pain. Literature offers few comparative data between different opioids at equianalgesic doses. Therefore morphine, fentanyl, buprenorphine, codeine, hydrocodone and oxycodone were compared for analgesic properties and side-effect profiles in rats. Analgesic efficacy was analysed using a tail withdrawal test for acute thermal nociception, a formalin test for chemically induced inflammatory pain and a von Frey test for mechanical hypersensitivity. For side-effect profiling inhibition of gastrointestinal activity was evaluated in a charcoal and ricinus oil test, arterial PCO(2) was determined for measuring respiratory depression, the discriminative stimulus properties linked to the narcotic cue were assessed using a drug discrimination learning test, and motor coordination was tested through rotarod performance. ED(50)'s for the occurrence of side-effects were compared to ED(50)'s in behavioural pain tests. Fentanyl had a strong analgesic potency and, compared to other opioids, an acceptable side-effect profiling at analgesic ED(50)'s. Also consistent was the ceiling effect of buprenorphine implying an increased safety margin for side-effects, but a decreased analgesic efficacy. Differences between opioids as observed in this study can have important indications for their use in acute as well as in the onset of chronic treatments.
authors.affiliation: CNS Pain and Alzheimer, J&J Pharmaceutical Research and Development, Turnhoutseweg 30, B-2340 Beerse, Belgium.
authors.forename: Theo F
authors.initials: TF
authors.lastname: Meert
authors.forename: Hilde A
authors.initials: HA
authors.lastname: Vermeirsch
mesh_terms: D000700:Analgesics / Q000008:administration & dosage* / Q000737:chemistry; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D004192:Discrimination, Psychological / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid