Toxicity of Dextromethorphan

Dextromethorphan is in the morphinan class of medications with dissociative, and stimulant properties (at lower doses). Dextromethorphan does not have a significant affinity for the mu-opioid receptor activity typical of morphinan compounds and exerts its therapeutic effects through several other receptors.[3] In its pure form, dextromethorphan occurs as a white powder.

Uses

Dextromethorphan is used therapeutically as an over-thecounter cough suppressant and antitussive. It is also commonly abused particularly by adolescents because of its relative ease of availability.

Mechanism of Toxicity

Dextromethorphan is the D-isomer of the codeine analog, methorphan. Unlike the L-isomer, it has no analgesic or addictive properties and does not act through the opioid receptors. The exact mechanism for the antitussive effect by dextromethorphan remains unclear and is likely multifactorial. Dextromethorphan is known to be an N-methyl-D-aspartate (NMDA) receptor antagonist; however, dextromethorphan binding sites are not limited to the known distribution of NMDA receptors.

Dextromethorphan’s main metabolite, dextrorphan, has NMDA receptor antagonist properties similar to ketamine and phencyclidine. This NMDA receptor antagonism is believed to result in a decreased reuptake of catecholamines. Dextromethorphan also inhibits the reuptake of serotonin. These properties make dextromethorphan have a high abuse and misuse potential.

Dextromethorphan is a common ingredient in over-thecounter cough and cold preparations, and is often combined with other agents including concurrent antihistamines, decongestants, analgesics, and ethanol. Patients may exhibit toxicity due to these coingestants.