The Monthly Index of Medical Specialities (MIMS) states under Anatomical Therapeutic Chemical (ATC) Classification: “R05DA09 – dextromethorphan; Belongs to the class of opium alkaloids and derivatives. Used as cough suppressant”. But your lecture and the textbooks say that dextromethorphan is a non-opioid antitussive. Why is there this discrepancy?

An opium alkaloid is an alkaloid found in opium. An opioid is a drug which acts at opioid receptors. The major active alkaloids in opium, such as morphine and codeine, act at opioid receptors.  They are both opium alkaloids and opioids. But not all opium alkaloids act at opioid receptors. Dextromethorphan is chemically an opium alkaloid derivative but it does not act at opioid receptors so pharmacologically it is not an opioid. It is a non-opioid opium alkaloid derivative.

Just as codeine is metabolised to morphine, dextromethorphan is converted to the more potent active metabolite dextrorphan. Dextrorphan is a dextro- (right-handed) enantiomer (dextrorotatory-stereoisomer) of which the corresponding levo- (left-handed) enantiomer is levorphanol, a potent opioid analgesic. Dextromethorphan and dextrorphan are right-handed enantiomers that do not act at the opioid receptor. They are therefore not opioids despite being opium alkaloid derivatives closely related to the potent opioid levorphanol.

The importance of dextromethorphan being a non-opioid is that does not share the same mechanisms of opioid dependence and addiction as codeine and so has a lower potential for abuse than codeine.  However, dextromethorphan is not utterly devoid of risk of abuse. Dextromethorphan is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist and at high doses has dissociative anaesthetic-like effects similar to ketamine and phencyclidine (PCP).