Dextrorphan (DXO) is a

psychoactive drug A psychoactive drug, psychopharmaceutical, mind-altering drug, consciousness-altering drug, psychoactive substance, or psychotropic substance is a chemical substance that alters psychological functioning by modulating central nervous system acti ...

of the morphinan class which acts as an antitussive or

cough suppressant Cold medicines are a group of medicinal, medications taken individually or in Combination drug, combination as a Symptomatic treatment, treatment for the symptoms of the common cold and similar conditions of the upper respiratory tract. The ter ...

and in high doses a dissociative

hallucinogen Hallucinogens, also known as psychedelics, entheogens, or historically as psychotomimetics, are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mo ...

. It is the dextrorotatory

enantiomer In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...

of racemorphan; the levorotatory enantiomer is levorphanol. Dextrorphan is produced by O-demethylation of

dextromethorphan Dextromethorphan, sold under the brand name Robitussin among others, is a cough suppressant used in many cough and Common cold, cold medicines. In 2022, the US Food and Drug Administration (FDA) approved the combination dextromethorphan/bupropi ...

by CYP2D6. Dextrorphan is an

NMDA antagonist NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the ''N''-Methyl-D-aspartate receptor ( NMDAR). They are commonly used as anesthetics for humans and animals; the state of anesthesia they ind ...

and contributes to the psychoactive effects of dextromethorphan.

Pharmacology

Pharmacodynamics

The pharmacology of dextrorphan is similar to that of

(DXM). However, dextrorphan is much more potent as an NMDA receptor antagonist and much less active as a serotonin reuptake inhibitor, but retains DXM's activity as a norepinephrine reuptake inhibitor. It also has more affinity for the opioid receptors than dextromethorphan, significantly so at high doses.

Pharmacokinetics

Dextrorphan has a notably longer

elimination half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...

than its parent compound, and therefore has a tendency to accumulate in the blood after repeated administration of normally dosed dextromethorphan formulations. It is further converted to 3-HM by

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

or glucuronidated.

Society and culture

Legal status

Dextrorphan was formerly a Schedule I controlled substance in the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

, but was unscheduled on October 1, 1976.

Research

Dextrorphan was under development for the treatment of

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

, and reached phase II

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

s for this indication, but development was discontinued.

Environmental presence

In 2021, dextrorphan was identified in >75% of sludge samples taken from 12

wastewater treatment Wastewater treatment is a process which removes and eliminates contaminants from wastewater. It thus converts it into an effluent that can be returned to the water cycle. Once back in the water cycle, the effluent creates an acceptable impact on ...

plants in

California California () is a U.S. state, state in the Western United States that lies on the West Coast of the United States, Pacific Coast. It borders Oregon to the north, Nevada and Arizona to the east, and shares Mexico–United States border, an ...

. The same study associated dextrorphan with estrogenic activity by using

predictive modelling Predictive modelling uses statistics to Prediction, predict outcomes. Most often the event one wants to predict is in the future, but predictive modelling can be applied to any type of unknown event, regardless of when it occurred. For example, pre ...

, before observing it in

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

References

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Pharmacodynamics Pharmacodynamics (PD) is the study of the biochemistry, biochemical and physiology, physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or comb ...

, titlestyle = background:#ccccff , list1 = {{Ionotropic glutamate receptor modulators {{Monoamine reuptake inhibitors {{Nicotinic acetylcholine receptor modulators {{Opioid receptor modulators {{Sigma receptor modulators Antitussives Dissociative drugs Enantiopure drugs Euphoriants Morphinans Mu-opioid receptor agonists Nicotinic antagonists NMDA receptor antagonists Hydroxyarenes Serotonin–norepinephrine reuptake inhibitors Sigma agonists Human drug metabolites