Dextrallorphan (DXA) is an chemical of the

morphinan Morphinan is the prototype chemical structure of a large chemical class of psychoactive drugs, consisting of opiate analgesics, cough suppressants, and dissociative hallucinogens, among others. Structure Morphinan has a phenanthrene core struct ...

class that is used in

scientific research The scientific method is an empirical method for acquiring knowledge that has characterized the development of science since at least the 17th century (with notable practitioners in previous centuries; see the article history of scientific m ...

. It acts as a σ₁ receptor agonist and NMDA receptor antagonist. It has no significant

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for the σ₂, μ-opioid, or

δ-opioid receptor The δ-opioid receptor, also known as delta opioid receptor or simply delta receptor, abbreviated DOR or DOP, is an inhibitory 7-transmembrane G-protein coupled receptor coupled to the G protein Gi/G0 and has enkephalins as its endogenous lig ...

, or for the serotonin or

norepinephrine transporter The norepinephrine transporter (NET), also known as noradrenaline transporter (NAT), is a protein that in humans is encoded by the solute carrier family 6 member 2 (SLC6A2) gene. NET is a monoamine transporter and is responsible for the sodium- ...

. As an NMDA receptor antagonist, ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

'', it is approximately twice as potent as

dextromethorphan Dextromethorphan (DXM) is a medication most often used as a cough suppressant in over-the-counter cold and cough medicines. It is sold in syrup, tablet, spray, and lozenge forms. In 2022, the FDA approved a formulation of it combined with bu ...

, and five-fold less potent than

dextrorphan Dextrorphan (DXO) is a psychoactive drug of the morphinan class which acts as an antitussive or cough suppressant and dissociative hallucinogen. It is the dextrorotatory enantiomer of racemorphan; the levorotatory enantiomer is levorphanol. D ...

Uses in Scientific Research

Masking of sigma-1 receptor

Dextrallorphan is often used in research to block σ₁ receptor sites so that σ₂ receptor sites (which have not been cloned yet ) can be studied. It was hypothesized that both of these sigma (σ) receptors were opioid receptors, due to their affinity for psychoactive drugs. However, it is now understood that they are non-opioid receptors that bind to certain psychoactive drugs, like dextrallorphan. One example of dextrallorphan being used to mask σ₁ receptor sites was seen in a study on the localization of the σ₂ receptor in detergent-resistant lipid raft domains. It has also been used to mask σ₁ receptor sites so that σ₂ receptor binding characteristics in the rat liver could be determined, by labeling σ₂ receptor sites with sup>3H,3-di-o-tolylguanidine (DTG) in the presence of 1 μM dextrallorphan solution.

Animal Studies

Dextrallorphan was used in Spraque-Dawley rats to study cerebellar Purkinje neurons electrophysical responses to the drug when it was applied iontophoretically as a sigma (σ) receptor ligand. Dextrallorphan increased the firing rate by 14%, suggesting that sigma (σ) ligands (like dextrallorphan) alter the spontaneous firing of Purkinje neurons and cause motor effects. In another study, dextrallorphan, along with other opioid derivatives, was found to be a potent inhibitor of etorphine-inaccessible (EI) sites in the guinea-pig brain. Dextrallorphan was of the top three most potent opioid inhibitors of those studied, with a concentration of 67 nM required to show 50% inhibition.

History

In 1955, dextrallorphan has been used to study inhibition of cholinesterases and to look at the relationship between analgetics and acetylcholine metabolism. It was found that dextrallorphan inhibits 25% of bovine erythrocyte cholinesterase at a dose of 10⁻³ mole/liter, which corresponds to a concentration of up to 0.2 mg/kg in dog intestine. However, at this dose the drug showed no effect on the gut tone. Dextrallorphan was classified as a potent inhibitor of the intestinal and red blood cell cholinesterase based on the concentration of the drug needed to inhibit these enzymes in the cholinesterase preparations from the animals systems utilized. Simultaneously, dextrallorphan showed no analgesia and no change in intestinal tone. With these results dextrallorphan helped proved that there is no correlation between the inhibition of cholinesterase systems and analgetic or intestinal effects. In 1979, dextrallorphan was found to have a half maximal inhibitory concentration (IC₅₀) for binding to the pituitary and brain receptor of 10,000 ± 1000 nM and 10,000 ± 1500 nM, respectively. While its stereoisomer, levallorphan, had a 10,000 times more potent dose, thus proving that binding to these receptors is stereospecific.

References

{{Sigma receptor modulators Phenols Morphinans NMDA receptor antagonists Sigma agonists

Uses in Scientific Research

Masking of sigma-1 receptor

Animal Studies

History

See also

References