Dextromethorphan, or DXM, a common active ingredient found in many over-the-counter cough suppressant cold medicines, is used as a recreational drug and entheogen for its dissociative effects. Street names include Brownies, Dextro, Drix, Gel, Groove, Lean, Mega-perls, Poor man's ecstasy, Red devils, Robo, Rojo, Rome, Skittles, Sizzurp, Sky and Velvet.
Dextrorphan (DXO) is a psychoactive drug of the morphinan class which acts as an antitussive or cough suppressant and in high doses a dissociative hallucinogen. It is the dextrorotatory enantiomer of racemorphan; the levorotatory enantiomer is levorphanol. Dextrorphan is produced by O-demethylation of dextromethorphan by CYP2D6. Dextrorphan is an NMDA antagonist and contributes to the psychoactive effects of dextromethorphan.
Noscapine is a benzylisoquinoline alkaloid, of the phthalideisoquinoline structural subgroup, which has been isolated from numerous species of the family Papaveraceae. It lacks significant hypnotic, euphoric, or analgesic effects affording it with very low addictive potential. This agent is primarily used for its antitussive (cough-suppressing) effects.
Dextromethorphan (DXM), sold under the trade name Robitussin among others, is a cough suppressant used in many cough and cold medicines. It affects serotonin, norepinephrine, NMDA, and sigma-1 receptors in the brain, all of which have been implicated in the pathophysiology of depression. In 2022, the FDA approved the combination dextromethorphan/bupropion to serve as a rapid acting antidepressant in patients with major depressive disorder.
Sigma receptors (σ-receptors) are protein receptors that bind ligands such as 4-PPBP, SA 4503 (cutamesine), ditolylguanidine, dimethyltryptamine, and siramesine. There are two subtypes, sigma-1 receptors (σ1) and sigma-2 receptors (σ2), which are classified as sigma receptors for their pharmacological similarities, even though they are evolutionarily unrelated.
Levorphanol is an opioid medication used to treat moderate to severe pain. It is the levorotatory enantiomer of the compound racemorphan. Its dextrorotatory counterpart is dextrorphan.
Levomethorphan (LVM) (INN, BAN) is an opioid analgesic of the morphinan family that has never been marketed. It is the L-stereoisomer of racemethorphan (methorphan). The effects of the two isomers of racemethorphan are quite different, with dextromethorphan (DXM) being an antitussive at low doses and a dissociative hallucinogen at much higher doses. Levomethorphan is about five times stronger than morphine.
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 induce is referred to as dissociative anesthesia.
Pentoxyverine (rINN) or carbetapentane is an antitussive commonly used for cough associated with illnesses like common cold. It is sold over-the-counter as Solotuss, or in combination with other medications, especially decongestants. One such product is Certuss, a combination of guaifenesin and pentoxyverine. The drug has been available in the form of drops, suspensions and suppositories.
Tipepidine (INN), also known as tipepidine hibenzate (JAN), is a synthetic, non-opioid antitussive and expectorant of the thiambutene class. It acts as an inhibitor of G protein-coupled inwardly-rectifying potassium channels (GIRKs). The drug was discovered in the 1950s, and was developed in Japan in 1959. It is used as the hibenzate and citrate salts.
Cloperastine (INN) or cloperastin, in the forms of cloperastine hydrochloride (JAN) and cloperastine fendizoate, is an antitussive and antihistamine that is marketed as a cough suppressant in Japan, Hong Kong, and in some European countries. It was first introduced in 1972 in Japan, and then in Italy in 1981.
Butamirate is a cough suppressant. It has been marketed in Europe and Mexico, but not in the United States.
Alazocine, also known more commonly as N-allylnormetazocine (NANM), is a synthetic opioid analgesic of the benzomorphan family related to metazocine, which was never marketed. In addition to its opioid activity, the drug is a sigma receptor agonist, and has been used widely in scientific research in studies of this receptor. Alazocine is described as a potent analgesic, psychotomimetic or hallucinogen, and opioid antagonist. Moreover, one of its enantiomers was the first compound that was found to selectively label the σ1 receptor, and led to the discovery and characterization of the receptor.
Racemorphan, or morphanol, is the racemic mixture of the two stereoisomers of 17-methylmorphinan-3-ol, each with differing pharmacology and effects:
The alpha-3 beta-4 nicotinic receptor, also known as the α3β4 receptor and the ganglion-type nicotinic receptor, is a type of nicotinic acetylcholine receptor, consisting of α3 and β4 subunits. It is located in the autonomic ganglia and adrenal medulla, where activation yields post- and/or presynaptic excitation, mainly by increased Na+ and K+ permeability.
Dextrallorphan (DXA) is a chemical of the morphinan class that is used in scientific research. It acts as a σ1 receptor agonist and NMDA receptor antagonist. It has no significant affinity for the σ2, μ-opioid, or δ-opioid receptor, or for the serotonin or norepinephrine transporter. As an NMDA receptor antagonist, in vivo, it is approximately twice as potent as dextromethorphan, and five-fold less potent than dextrorphan.
Dextromethorphan/quinidine, sold under the brand name Nuedexta, is a fixed-dose combination medication for the treatment of pseudobulbar affect (PBA). It contains dextromethorphan (DXM) and the class I antiarrhythmic agent quinidine.
Dextromethorphan/bupropion (DXM/BUP), sold under the brand name Auvelity, is a combination medication for the treatment of major depressive disorder (MDD). Its active components are dextromethorphan (DXM) and bupropion. Patients who stayed on the medication had an average of 11% greater reduction in depressive symptoms than placebo in an FDA approval trial. It is taken as a tablet by mouth.
Fominoben is an antitussive agent of the benzanilide class, formerly marketed under the name Noleptan. It binds poorly to the sigma-1 receptor, a receptor activated by many other antitussives. It is reported to have respiratory stimulant activity. Other research has indicated it may be an agonist at the benzodiazepine site of the GABAA receptor. It was introduced in Germany in 1973, in Italy in 1979, and in Japan in 1983.
Deudextromethorphan/quinidine is a combination of deudextromethorphan and quinidine (Q) which is under development by Avanir Pharmaceuticals for the treatment of a variety of neurological and psychiatric indications. The pharmacological profile of d-DXM/Q is similar to that of dextromethorphan/quinidine (DXM/Q). DXM and d-DXM act as σ1 receptor agonists, NMDA receptor antagonists, and serotonin–norepinephrine reuptake inhibitors, among other actions, while quinidine is an antiarrhythmic agent acting as a CYP2D6 inhibitor. Quinidine inhibits the metabolism of DXM and d-DXM into dextrorphan (DXO), which has a different pharmacological profile from DXM. Deuteration of DXM hinders its metabolism by CYP2D6 into DXO, thereby allowing for lower doses of quinidine in the combination. This in turn allows for lower potential for drug interactions and cardiac adverse effects caused by quinidine. As of September 2020, d-DXM/Q is in phase 3 clinical trials for agitation, phase 2/3 trials for schizophrenia, and phase 2 trials for brain injuries, impulse control disorders, major depressive disorder, and neurodegenerative disorders.
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