A preclinical comparison between different opioids: antinociceptive versus adverse effects.
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.
Meert
Theo F
TF
CNS Pain and Alzheimer, J&J Pharmaceutical Research and Development, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Vermeirsch
Hilde A
HA
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
D000700:Analgesics; D000701:Analgesics, Opioid