Meperidine (Pethidine): A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

Meperidine, also known by its international nonproprietary name pethidine and the brand name Demerol®, is a fully synthetic opioid analgesic of the phenylpiperidine class.[1] First synthesized in the 1930s, it occupied a prominent position in clinical practice for much of the 20th century, often preferred by physicians for the management of moderate-to-severe acute pain under the now-disproven belief that it carried a lower risk of addiction and was superior to morphine for certain types of pain.[1] However, a contemporary, evidence-based understanding of its complex pharmacology and significant risk profile has led to a dramatic re-evaluation of its clinical utility. Today, its use is highly restricted and relegated to a few niche, short-term applications.

The central thesis of this monograph is that meperidine's clinical value is severely constrained by an unfavorable risk-benefit profile. This profile is dominated by two key factors: the central nervous system (CNS) neurotoxicity of its active metabolite, normeperidine, and a high potential for severe, often fatal, drug interactions. The pharmacokinetic mismatch between the short-acting parent drug and its long-acting toxic metabolite creates a predictable pathway to accumulation and toxicity, particularly with repeated dosing or in patients with compromised renal function. Normeperidine-induced neurotoxicity manifests as a spectrum of CNS hyperexcitability, including tremors, myoclonus, and grand mal seizures, which are not reversible with the opioid antagonist naloxone.[3]