Dextrallorphan

Dextrallorphan is often used in research to block σ₁ receptor sites so that σ₂ receptor sites (which have not been cloned yet {{when?|date=May 2019}}) can be studied.{{cite journal | vauthors = Gebreselassie D, Bowen WD | title = Sigma-2 receptors are specifically localized to lipid rafts in rat liver membranes | journal = European Journal of Pharmacology | volume = 493 | issue = 1–3 | pages = 19–28 | date = June 2004 | pmid = 15189760 | doi = 10.1016/j.ejphar.2004.04.005 | url = https://zenodo.org/record/1258913 }}{{cite journal | vauthors = Maeda DY, Williams W, Bowen WD, Coop A | title = A sigma-1 receptor selective analogue of BD1008. A potential substitute for (+)-opioids in sigma receptor binding assays | journal = Bioorganic & Medicinal Chemistry Letters | volume = 10 | issue = 1 | pages = 17–8 | date = January 2000 | pmid = 10636233 | doi = 10.1016/s0960-894x(99)00590-9 }}{{cite journal | vauthors = Torrence-Campbell C, Bowen WD | title = Differential solubilization of rat liver sigma 1 and sigma 2 receptors: retention of sigma 2 sites in particulate fractions | journal = European Journal of Pharmacology | volume = 304 | issue = 1–3 | pages = 201–10 | date = May 1996 | pmid = 8813603 | doi = 10.1016/0014-2999(96)00109-4 | url = https://zenodo.org/record/1253872 }}

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.{{cite journal | vauthors = Hayashi T, Su T | title = The sigma receptor: evolution of the concept in neuropsychopharmacology | journal = Current Neuropharmacology | volume = 3 | issue = 4 | pages = 267–80 | date = October 2005 | pmid = 18369400 | pmc = 2268997 | doi = 10.2174/157015905774322516 }}

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 [³H]l,3-di-o-tolylguanidine (DTG) in the presence of 1 μM dextrallorphan solution.

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.{{cite journal | vauthors = Martin WJ, De Costa BR, Walker JM | title = Effects of sigma ligands on rat cerebellar Purkinje neuron firing: an iontophoretic study | journal = Brain Research Bulletin | volume = 35 | issue = 4 | pages = 303–9 | date = 1994 | pmid = 7850479 | doi = 10.1016/0361-9230(94)90106-6 | s2cid = 54255450 }}

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.

{{Primary sources|section|date=December 2014}}

In 1955, dextrallorphan has been used to study inhibition of cholinesterases and to look at the relationship between analgetics and acetylcholine metabolism.{{cite journal | vauthors = Eikenburg DC, Stickney JL | title = Anti-cholinesterase activity of 1-alpha-acetylmethadol: relationship to bradycardia | journal = General Pharmacology | volume = 10 | issue = 3 | pages = 195–200 | date = 1979 | pmid = 467958 | doi = 10.1016/0306-3623(79)90089-2 }}

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.{{cite journal | vauthors = Young DC, Ploeg RA, Featherstone RM, Gross EG | title = The interrelationships among the central, peripheral and anticholinesterase effects of some morphinan derivatives | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 114 | issue = 1 | pages = 33–7 | date = May 1955 | pmid = 14392568 | url = http://jpet.aspetjournals.org/content/114/1/33.long | format = pdf }}

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.{{cite journal | vauthors = Simantov R, Snyder SH | title = Opiate receptor binding in the pituitary gland | journal = Brain Research | volume = 124 | issue = 1 | pages = 178–84 | date = March 1977 | pmid = 191146 | doi = 10.1016/0006-8993(77)90877-0 | s2cid = 40173550 }}

• Morphinan
• Oxilorphan
• Dextrorphan
• Dextromethorphan
• Levallorphan

{{Reflist|2}}

{{Hallucinogens}}

{{Ionotropic glutamate receptor modulators}}

{{Sigma receptor modulators}}

Category:Hydroxyarenes

Category:Morphinans

Category:NMDA receptor antagonists

Category:Sigma agonists