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Drug Res (Stuttg) 2016; 66(11): 562-570
DOI: 10.1055/s-0042-109393
Review
© Georg Thieme Verlag KG Stuttgart · New York

Efficacy of Full µ-Opioid Receptor Agonists is not Impaired by Concomitant Buprenorphine or Mixed Opioid Agonists/Antagonists – Preclinical and Clinical Evidence

J. C. G. van Niel
1   Grünenthal GmbH, Global Late Stage Clinical Development, Aachen, Germany
,
J. Schneider
2   Grünenthal GmbH, Global Innovation, Research, Aachen, Germany
,
T. M. Tzschentke
3   Grünenthal GmbH, Pharmacology and Biomarker Development, Aachen, Germany
› Author Affiliations
Further Information

Publication History

received 28 April 2016

accepted 24 May 2016

Publication Date:
09 August 2016 (online)

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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.

Key words

analgesic drugs - drug research - pharmacology
 

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