IUPAC Name
(+)-3-methoxy-17-methyl-(9α,13α,14α)-morphinan
Current Scheduling Status
None
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Discussion
Dextromethorphan is (+)-3-methoxy-17-methyl-(9α,13α,14α)-morphinan. During the fourth meeting of the ECDD in 1953 (then: Expert Committee on Drugs Liable to Produce Addiction), the synthetic substances of the morphinan type, including dextromethorphan, were discussed (20). After reviewing the worldwide reports at that time, the Expert Committee concluded that dextromethorphan has no morphine-like actions, lacks the ability to sustain morphine dependence, and exhibited no signs of dependence liability. Therefore, the Expert Committee recommended against placing dextromethorphan under control of the Conventions. In order to update the scientific evidence on dextromethorphan, a member of the Expert Committee proposed that it be pre-reviewed.
Dextromethorphan is the d-isomer of the codeine analogue methorphan; however, unlike the l-isomer, it does not act through opioid receptors. Dextromethorphan binds with high affinity to sites associated with sigma ligands and low affinity to the phencyclidine (PCP) binding site of the N-methyl-D-aspartate (NMDA) receptor. The relationship of these receptor binding sites to the pharmacological mechanism of the antitussive effects of dextromethorphan is not known. Dextromethorphan produces PCP-like discriminative stimulus effects in rats and partial substitution for PCP in monkeys probably produced by the metabolite dextrorphan. Dextromethorphan can alter self-administration of several substances of abuse such as morphine, cocaine, and methamphetamine. Few data exist on dextromethorphan dependence, with only a handful of cases described in scientific literature. Cases of abuse of dextromethorphan have been reported in several countries. However, these reports are still relatively infrequent. Dextromethorphan is produced commercially in many regions of the world, but synthesis is a complex and time-consuming process, making clandestine production impractical. Dextromethorphan is widely used as an antitussive in many over-the-counter and prescription-only preparations.
Recommendation
Following review of the documents presented at the thirty-fifth meeting, the Expert Committee concluded that the abuse potential of dextromethorphan is relatively low, intoxications are rare, and reports of dependence are infrequent. Dextromethorphan is widely used as an antitussive agent and placing it under international control could negatively impact its availability for medical use. On this basis, the Expert Committee concluded that a critical review is not warranted at this time.
Dextromethorphan is (+)-3-methoxy-17-methyl-(9α,13α,14α)-morphinan. During the fourth meeting of the ECDD in 1953 (then: Expert Committee on Drugs Liable to Produce Addiction), the synthetic substances of the morphinan type, including dextromethorphan, were discussed (20). After reviewing the worldwide reports at that time, the Expert Committee concluded that dextromethorphan has no morphine-like actions, lacks the ability to sustain morphine dependence, and exhibited no signs of dependence liability. Therefore, the Expert Committee recommended against placing dextromethorphan under control of the Conventions. In order to update the scientific evidence on dextromethorphan, a member of the Expert Committee proposed that it be pre-reviewed.
Dextromethorphan is the d-isomer of the codeine analogue methorphan; however, unlike the l-isomer, it does not act through opioid receptors. Dextromethorphan binds with high affinity to sites associated with sigma ligands and low affinity to the phencyclidine (PCP) binding site of the N-methyl-D-aspartate (NMDA) receptor. The relationship of these receptor binding sites to the pharmacological mechanism of the antitussive effects of dextromethorphan is not known. Dextromethorphan produces PCP-like discriminative stimulus effects in rats and partial substitution for PCP in monkeys probably produced by the metabolite dextrorphan. Dextromethorphan can alter self-administration of several substances of abuse such as morphine, cocaine, and methamphetamine. Few data exist on dextromethorphan dependence, with only a handful of cases described in scientific literature. Cases of abuse of dextromethorphan have been reported in several countries. However, these reports are still relatively infrequent. Dextromethorphan is produced commercially in many regions of the world, but synthesis is a complex and time-consuming process, making clandestine production impractical. Dextromethorphan is widely used as an antitussive in many over-the-counter and prescription-only preparations.
Recommendation
Following review of the documents presented at the thirty-fifth meeting, the Expert Committee concluded that the abuse potential of dextromethorphan is relatively low, intoxications are rare, and reports of dependence are infrequent. Dextromethorphan is widely used as an antitussive agent and placing it under international control could negatively impact its availability for medical use. On this basis, the Expert Committee concluded that a critical review is not warranted at this time.
ECDD Recommendation
No change in scheduling
Link to full TRS
who_trs_973_eng.pdf1.73 MB
MS Questionnaire Report