Zomepirac: preclinical narcotic abuse liability evaluation

Area of Science:

• Pharmacology
• Neuroscience
• Drug Abuse Research

Background:

• Zomepirac (Zomax) is a non-steroidal anti-inflammatory drug.
• Narcotic analgesics possess distinct pharmacological profiles and abuse liability.
• Understanding Zomepirac's interaction with opioid systems is crucial for assessing its safety.

Purpose of the Study:

• To evaluate the pharmacological profile of Zomepirac in relation to narcotic agonists and antagonists.
• To determine if Zomepirac exhibits characteristics associated with opioid-like drugs, particularly concerning abuse potential.

Main Methods:

• Assessment of Zomepirac's ability to displace radiolabeled etorphine from opioid receptors.
• Evaluation of Zomepirac's effects on isolated tissues (guinea pig ileum, mouse vas deferens) and its interaction with narcotic antagonists.
• Testing Zomepirac's efficacy in various analgesic assays (tail-flick, hot plate, Nilsen) and as a morphine antagonist.
• Investigating Zomepirac's effects on naloxone-reversible writhing responses.
• Assessing Zomepirac's impact on morphine withdrawal signs in dependent rhesus monkeys.
• Examining Zomepirac's potential to induce dependence and support drug self-administration in animal models.
• Utilizing drug discrimination assays in rhesus monkeys to compare Zomepirac's effects with known narcotic agonists.

Main Results:

• Zomepirac did not significantly displace etorphine, indicating weak opioid receptor interaction.
• While active on guinea pig ileum and mouse vas deferens, Zomepirac's effects were less efficacious than morphine and not reversed by narcotic antagonists.
• Zomepirac was inactive in several analgesic assays and as a morphine antagonist.
• Zomepirac showed activity in the phenylquinone writhing assay, but this was not reversed by naloxone.
• Zomepirac did not suppress morphine withdrawal signs, induce dependence, support self-administration, or produce drug-appropriate responding in discrimination studies.

Conclusions:

• Zomepirac exhibits minimal to no characteristic actions of narcotics.
• The findings suggest Zomepirac has a low potential for abuse and does not interact significantly with the opioid system.
• Zomepirac's pharmacological profile is distinct from that of narcotic analgesics.