On subclasses of opioid analgesics

Abstract

Background:

The history of discovery of analgesic drugs has followed a trajectory from original serendipitous discovery of plant-derived substances to laboratory creation of customized molecules that are intentionally designed to interact with specific receptors of neurotransmitters involved in either the transmission of the pain signal or the attenuation of such a signal. The drugs most recently developed have been designed to provide incremental greater separation between pain relief and adverse effects. The result has been drugs that have individualized pharmacodynamic and pharmacokinetic characteristics that represent specific advances in basic science and translate into unique clinical profiles. Several of the drugs include non-opioid components. They retain some of the features of opioids, but have distinct clinical characteristics that differentiate them from traditional opioids. Thus they defy simple classification as opioids.

Scope:

A summary is provided of the development of the modern view of multi-mechanistic pain and its treatment using analgesics that have multi-mechanisms of action (consisting of both opioid and non-opioid components). Descriptions of examples of such current analgesics and of those that have pharmacokinetic characteristics that result in atypical opioid clinical profiles are given.

Findings:

By serendipity or design, several current strong analgesics have opioid components of action, but have an additional non-opioid mechanism of action or some pharmacokinetic feature that gives them an atypical opioid clinical profile and renders them not easily classified as classical opioids.

Conclusion:

An appreciation that there are now opioid analgesics that differentiate from classical opioids in ways that defy their simplistic classification as opioids suggests that recognition of subclasses of opioid analgesics would be more accurate scientifically and would be more informative for healthcare providers and regulators. This would likely lead to positive outcomes for the clinical use and regulatory control of the current drugs, and provide direction/strategy for the discovery of new drugs.

Key words::

• Analgesics (opioid)
• Clinical attributes
• Drug classification
• Mechanism of action
• Opioid categories
• Regulatory controls

Transparency

Declaration of funding

Funding for this publication was provided by Johnson & Johnson.

Declaration of financial/other relationships

R.B.R. has disclosed that he is a former employee of Johnson & Johnson. He has also received honoraria, consultancy fees and/or research funding from Adolor, Alteon, Ampio/Vyrix, Asta medica, Discover res Consultants, Endo, Galleon, Grunenthal, Inspirion, Iroko, Janssen, Johnson & Johnson, Kiraz, Labo Pharm, LAPID, Mallinckrodt/Coviden, Novartis, Onconova, Pain Thereapeutics, Pfizer and Purdue Pharma.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work. Peer reviewer 1 has disclosed that he is a consultant for Insys, Baxter, Purdue Pharma LLP, Grunenthal Gmbh, and Johnson and Johnson, but has no relationship to this specific research. Peer reviewer 2 has no relevant financial or other relationships to disclose.

Notes

*Imodium is a registered trade name of McNEIL-PPC, Inc (Ft Washington, PA).