title: Efficacy of Full µ-Opioid Receptor Agonists is not Impaired by Concomitant Buprenorphine or Mixed Opioid Agonists/Antagonists - Preclinical and Clinical Evidence.
abstract: Buprenorphine and the mixed agonists/antagonists nalbuphine and pentazocine, formerly classified as µ-opioid (MOP) receptor antagonists, have more recently been shown to be partial to full agonists of the human MOP receptor. These receptors do not necessarily have to be maximally activated for a full physiological response. Partial agonists can also sufficiently stimulate signaling processes leading to a full analgesic response, as shown by the effectiveness of buprenorphine, nalbuphine and pentazocine in animal pain models and in clinical settings where these drugs induce analgesia with full efficacy without a ceiling effect. Submaximal doses of MOP receptor analgesics combined with submaximal doses of buprenorphine, pentazocine, or nalbuphine result in additive to over-additive antinociceptive effects in animal experiments. Only when doses are given that exceed the therapeutic dose range may the antinociceptive effect be reduced to the effect of either opioid alone. The analgesic effects of pentazocine and nalbuphine combined with morphine are reported to be additive or over-additive in various clinical pain conditions. Buprenorphine, which clinically behaves as a full MOP receptor agonist for pain relief, can be combined with full opioid agonists without precipitating withdrawal. Thus, the overall evidence on the analgesic effects of buprenorphine, pentazocine or nalbuphine combined with opioid analgesics under various clinical pain conditions contradicts the consensus that these compounds diminish MOP receptor analgesia when co-administered with a full MOP receptor agonist.
authors: Grünenthal GmbH, Global Late Stage Clinical Development, Aachen, Germany.
authors: J C G
authors: JC
authors: van Niel
authors: Grünenthal GmbH, Global Innovation, Research, Aachen, Germany.
authors: J
authors: J
authors: Schneider
authors: Grünenthal GmbH, Pharmacology and Biomarker Development, Aachen, Germany.
authors: T M
authors: TM
authors: Tzschentke
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D002047:Buprenorphine / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D009266:Nalbuphine / Q000494:pharmacology / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy; D010423:Pentazocine / Q000494:pharmacology / Q000627:therapeutic use; D011957:Receptors, Opioid / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D002047:Buprenorphine; D009266:Nalbuphine; D010423:Pentazocine