Dextromethorphan (DXM or DM) is an antitussive (cough suppressant) drug found in many over-the-counter cold and cough medicines. Dextromethorphan has also found other uses in medicine, ranging from pain relief to psychological applications. Pure dextromethorphan occurs as a powder made up of white crystals, but it is generally administered via syrups, tablets, or lozenges manufactured under several different brand names and generic labels. In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body. ... A cough medicine is a drug used to treat coughing and related conditions. ... Over-the-counter (OTC) drugs are medicines that may be sold without a prescription, in contrast to prescription drugs. ... Acute viral nasopharyngitis, or acute coryza, usually known as the common cold, is a highly contagious, viral infectious disease of the upper respiratory system, primarily caused by picornaviruses or coronaviruses. ... Cough medicine often contains cough suppressants and expectorants. ... This does not cite its references or sources. ... Look up Generic in Wiktionary, the free dictionary. ...

When taken at doses higher than are medically recommended, dextromethorphan acts as a dissociative hallucinogenic drug. It is classified neurochemically as an NMDA receptor antagonist, producing effects similar to those of the controlled substances ketamine and phencyclidine (PCP),^[2] which affords it a significant potential for abuse.^[3] Dissociative drugs are a class of psychedelic drugs characterized by intense feelings of depersonalization, derealization, and analgesia. ... Hallucinogenic drug - drugs that can alter sensory perceptions. ... NMDA receptor antagonists are a class of anesthetics that work to antagonize, or inhibit the action of, the NMDA receptor (NMDAR). ... Ketamine is a dissociative anesthetic for use in human and veterinary medicine developed by Parke-Davis (1962). ... Phencyclidine (a contraction of the chemical name phenylcyclohexylpiperidine), abbreviated PCP, is a dissociative drug formerly used as an anesthetic agent, exhibiting hallucinogenic and neurotoxic effects. ...

Chemistry

Dextromethorphan is the dextrorotatory enantiomer of the methyl ether of levorphanol, a narcotic analgesic. It is also a stereoisomer of levomethorphan, an opioid analgesic. It is named according to IUPAC rules as (+)-3-methoxy-17-methyl-9α,13α,14α-morphinan. As the pure free base, dextromethorphan occurs as an odorless, white to slightly yellow crystalline powder. It is freely soluble in chloroform and essentially insoluble in water. Commercially, dextromethorphan is commonly available as the monohydrated hydrobromide salt, although some newer extended-release formulations contain dextromethorphan bound to an ion exchange resin based on polystyrene sulfonic acid. Dextromethorphan's specific rotation in water is +27.6° (20°C, Sodium D-line). Dextrorotation is the property of rotating plane polarized light clockwise. ... In chemistry, enantiomers (from the Greek ἐνάντιος, opposite, and μέρος, part or portion) are stereoisomers that are nonsuperimposable complete mirror images of each other, much as ones left and right hands are the same but opposite. ... This article is about a general class of chemical compounds. ... Levorphanol is an opioid medication used to treat severe pain. ... Stereoisomerism is the arrangement of atoms in molecules whose connectivity remains the same but their arrangement in space is different in each isomer. ... Levomethorphan is an optical isomer of dextromethorphan. ... An opioid is a chemical substance that has a morphine-like action in the body. ... An analgesic (colloquially known as a painkiller) is any member of the diverse group of drugs used to relieve pain (achieve analgesia). ... The International Union of Pure and Applied Chemistry (IUPAC) is an international non-governmental organization devoted to the advancement of chemistry. ... Morphinan is the base chemical structures of a subgroup of opioids. ... R-phrases , , , S-phrases , Flash point Non-flammable U.S. Permissible exposure limit (PEL) 50 ppm (240 mg/m3) (OSHA) Supplementary data page Structure and properties n, εr, etc. ... Impact from a water drop causes an upward rebound jet surrounded by circular capillary waves. ... Polystyrene sulfonate Sodium polystyrene sulfonate is a type of polymer and ionomer based on polystyrene. ... The specific rotation of a chemical compound [α] is defined as the observed angle of optical rotation α when plane-polarized light is passed through a sample with a path length of 1 decimeter and a sample concentration of 1 gram per 1 millilitre. ...

Indications

The primary use of dextromethorphan is as a cough suppressant, for the temporary relief of cough caused by minor throat and bronchial irritation (as commonly accompanies the common cold), as well as other causes such as inhaled irritants.

Additionally, a combination of dextromethorphan and quinidine has been shown to alleviate symptoms of easy laughing and crying (pseudobulbar affect) in patients with amyotrophic lateral sclerosis and multiple sclerosis.^[4] Dextromethorphan is also being investigated as a possible treatment for neuropathic pain and pain associated with fibromyalgia.^[5] Quinidine is a pharmaceutical agent that acts as a class I antiarrhythmic agent in the heart. ... Labile affect or Pseudobulbar affect refers to the pathological expression of laughter, crying, or smiling. ... Amyotrophic Lateral Sclerosis (ALS, sometimes called Lou Gehrigs Disease, or Maladie de Charcot) is a progressive, usually fatal, neurodegenerative disease caused by the degeneration of motor neurons, the nerve cells in the central nervous system that control voluntary muscle movement. ... Neuropathy is a disease of the peripheral nervous system. ... Fibromyalgia (FM) is stated to be a disorder classified by the presence of chronic widespread pain and tactile allodynia. ...

Pharmacokinetics

At therapeutic doses, dextromethorphan acts centrally (meaning that it acts on the brain) as opposed to locally (on the respiratory tract). It elevates the threshold for coughing, without inhibiting ciliary activity. Dextromethorphan is rapidly absorbed from the gastrointestinal tract and converted into an active metabolite within 15 to 60 minutes of ingestion. The average dosage necessary for effective antitussive therapy is between 15 mg and 60 mg, depending on age. The duration of action after oral administration is approximately three to eight hours for dextromethorphan-hydrobromide, and ten to twelve hours for dextromethorphan-polistirex. A diagram showing the CNS: 1. ... For other uses, see Brain (disambiguation). ... In humans the respiratory tract is the part of the anatomy that has to do with the process of respiration or breathing. ... cross-section of two cilia, showing 9+2 structure A cilium (plural cilia) is a fine projection from a eukaryotic cell that constantly beats in one direction. ... Gut redirects here. ...

Because administration of dextromethorphan can trigger a histamine release (an allergic reaction), its use in atopic children is very limited. This article or section does not cite any references or sources. ... This article needs cleanup. ... In medicine, the atopic syndrome is the clustering of eczema, allergic conjunctivitis, allergic rhinitis and asthma in certain individuals. ...

Side-effects

Side-effects of dextromethorphan use can include:^[6]

Can also cause increases in: A rash is a change in skin which affects its color, appearance, or texture. ... An itch (Latin: pruritus) is a sensation felt on an area of skin that makes a person or animal want to scratch it. ... For other uses, see Nausea (disambiguation). ... Somnolence (or drowsiness, or hypersomnia) is a state of near-sleep, a strong desire for sleep, or sleeping unusually long periods. ... Many different terms are often used to describe what is collectively known as dizziness. ... Excitation is the amount of energy (energy in a general sense, not energy as defined in physics) that Curtis has. ... Heaving redirects here. ... // Mydriasis is an excessive dilation of the pupil due to disease or drugs. ... Perspiration (also called sweating or sometimes transpiration) is the production and evaporation of a fluid, consisting primarily of water as well as a smaller amount of sodium chloride (the main constituent of table salt), that is excreted by the sweat glands in the skin of mammals. ... An analogue medical thermometer showing the temperature of 38. ... For other forms of hypertension, see Hypertension (disambiguation). ... Among quadrupeds, the respiratory system generally includes tubes, such as the bronchi, used to carry air to the lungs, where gas exchange takes place. ... In medicine, diarrhea, also spelled diarrhoea (see spelling differences), refers to frequent loose or liquid bowel movements. ... Urinary retention also known as ischuria is a lack of ability to urinate. ...

Dextromethorphan can also cause other gastrointestinal disturbances. When injected directly into the blood stream, some studies suggest that dextromethorphan has the potential to cause Olney's Lesions.^[7][8] In some rare documented cases, dextromethorphan has produced psychological dependence in people who abused it. However, it does not produce physical addiction, according to the WHO Committee on Drug Dependence. Heart rate is the frequency of the cardiac cycle. ... A sphygmomanometer, a device used for measuring arterial pressure. ... Thermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even when temperature surrounding is very different. ... Olneys Lesions, also known as NMDA Receptor Antagonist Neurotoxicity (NAN), are a form of brain damage theorized to be caused by high doses of dissociative anaesthetics, particularly those referred to as noncompetitive NMDA-channel-blockers such as ketamine, phencyclidine, and dextromethorphan. ... This article is about the concept of addiction. ... WHO redirects here. ...

Drug interactions

Dextromethorphan should not be taken with either of the following:

• monoamine oxidase inhibitors (MAOIs)^[6]
• selective serotonin reuptake inhibitors (SSRIs)^[6]

CNS depressant drugs and substances, including alcohol, antihistamines, and some psychotropics, will have a cumulative CNS depressant effect if taken with dextromethorphan.^[6] MAOI redirects here. ... SSRI redirects here; for other uses, see SSRI (disambiguation). ... See also sedative. ... An antihistamine is a drug which serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions, through action at the histamine receptor. ... An assortment of psychoactive drugs A psychoactive drug or psychotropic substance is a chemical substance that acts primarily upon the central nervous system where it alters brain function, resulting in temporary changes in perception, mood, consciousness and behavior. ...

Contraindications

Because dextromethorphan can trigger a histamine release (allergic reaction), atopic children, who are especially susceptible to allergic reactions, should be administered dextromethorphan only if absolutely necessary, and only under the strict supervision of a health care professional.^[6] In medicine, the atopic syndrome is the clustering of eczema, allergic conjunctivitis, allergic rhinitis and asthma in certain individuals. ...

Clinical pharmacology

Following oral administration, dextromethorphan is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood-brain barrier. The first-pass through the hepatic portal vein results in some of the drug being metabolized into an active metabolite of dextromethorphan, dextrorphan, the 3-hydroxy derivative of dextromethorphan. The therapeutic activity of dextromethorphan is believed to be caused by both the drug and this metabolite. Dextromethorphan is metabolized by various liver enzymes and subsequently undergoes O-demethylation (producing dextrorphan), N-demethylation, and partial conjugation with glucuronic acid and sulfate ions. Hours after dextromethorphan therapy, (in humans) the metabolites (+)-3-hydroxy-N-methylmorphinan, (+)-3-morphinan, and traces of the unchanged drug are detectable in the urine.^[6] The blood-brain barrier (BBB) is a membranic structure that acts primarily to protect the brain from chemicals in the blood, while still allowing essential metabolic function. ... A metabolite is the product of metabolism. ... Dextrorphan is a pharmacologically active metabolite of Dextromethorphan (DXM). ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... This article is about the urine of animals generally. ...

A major metabolic catalyst involved is the cytochrome P450 enzyme known as 2D6, or CYP2D6. A significant portion of the population has a functional deficiency in this enzyme and are known as poor CYP2D6 metabolizers. As CYP2D6 is a major metabolic pathway in the inactivation of dextromethorphan, the duration of action and effects of dextromethorphan can be increased by as much as three times in such poor metabolizers.^[9] Cytochrome P450 Oxidase (CYP2E1) Cytochrome P450 oxidase (commonly abbreviated CYP) is a generic term for a large number of related, but distinct, oxidative enzymes (EC 1. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... Cytochrome P450 2D6 (CYP2D6), a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. ... In biochemistry, a metabolic pathway is a series of chemical reactions occurring within a cell. ...

A large number of medications (including antidepressants) are potent inhibitors of CYP2D6. There exists, therefore, the potential of interactions between dextromethorphan and concomitant medications. Dextromethorphan crosses the blood-brain barrier, and the following pharmacological actions have been reported: Prozac, a selective serotonin reuptake inhibitor (SSRI) Serotonin-norepinephrine reuptake inhibitor, Venlafaxine An antidepressant is a psychiatric medication or other substance (nutrient or herb) used for alleviating depression or dysthymia (milder depression). ... Cytochrome P450 2D6 (CYP2D6), a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. ... The blood-brain barrier (BBB) is a membranic structure that acts primarily to protect the brain from chemicals in the blood, while still allowing essential metabolic function. ...

• NMDA receptor antagonist
• σ₁ and σ₂ receptor agonist.^[10]
• α3β4 nicotinic receptor antagonist^[11]
• Serotonin reuptake inhibitor^[12]
• Dopamine reuptake inhibitor (disputed)^[6][13]

NMDA receptor antagonists are a class of anesthetics that work to antagonize, or inhibit the action of, the NMDA receptor (NMDAR). ... The sigma-1 receptor is a transmembrane protein expressed in many different tissue types. ... Opioid receptors are a group of G-protein coupled receptors with opioids as ligands. ... Nicotinic acetylcholine receptors, or nAChRs, are ionotropic receptors that form ion channels in cells plasma membranes. ... Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants. ... This does not cite any references or sources. ...

Brand names

Dextromethorphan is an active ingredient in many brand-name cough suppressant preparations, including:

Benylin This is a powerful cough mixture that has a chemical that stops the coughing reflex. ... W.K. Buckley Limited is a Canadian corporation founded in 1990, by W.K. Buckley, that manufactures medicines for health problems such as the common cold. ... Coricidin, Coricidin D (decongestant), or CoricidinHBP (for high blood pressure), is the name of a drug marketed by Schering-Plough that contains dextromethorphan (a cough suppressant) and chlorphenamine maleate (an antihistamine). ... Delsym is an American brand of over-the-counter cough medicine. ... Robitussin is a brand of cold and cough medicines produced by Wyeth Consumer Healthcare. ... 50g Vicks VapoRub. ...

History

Dextromethorphan was first patented under U.S. Patent 2,676,177 . The FDA approved dextromethorphan for over-the-counter sale as a cough suppressant in 1958. This filled the need for a cough suppressant lacking the sedative side-effects, stronger potential for abuse, and physically addictive properties of codeine phosphate, the most widely-used cough medication at the time (now prescription-only in the United States).^[14] As with most cough suppressants, studies show that dextromethorphan's effectiveness is highly debatable,^[15] especially in children.^[16] The United States Food and Drug Administration is the government agency responsible for regulating food, dietary supplements, drugs, cosmetics, medical devices, biologics and blood products in the United States. ... Over-the-counter (OTC) drugs are medicines that may be sold without a prescription, in contrast to prescription drugs. ... For the band, see Codeine (band). ... Cough medicine often contains cough suppressants and expectorants. ...

During the 1960s and 1970s, dextromethorphan became available in an over-the-counter tablet form by the brand name Romilar. In 1973, Romilar was taken off the shelves after a burst in sales due to frequent abuse, and was replaced by cough syrup in an attempt to cut down on abuse.^[14] Dextromethorphan hydrobromide (DXM for short) is an antitussive drug that is found in many over-the-counter cold remedies and cough syrups. ...

More recently (around 2000) gel capsule forms began reappearing in the form of Robitussin CoughGels as well as several generic forms of that preparation.

Recreational use

Main article: Non-medical use of dextromethorphan

Since their introduction, over-the-counter preparations containing dextromethorphan have been used in a manner inconsistent with their labeling, often as a recreational drug.^[14] At doses higher than medically recommended, dextromethorphan is classified as a dissociative hallucinogenic drug, with visible effects that are similar to ketamine and phencyclidine (PCP). It has been suggested that Triple C be merged into this article or section. ... Over-the-counter substances, also abbreviated OTC, are drugs and other medical remedies that may be sold without a prescription and without a visit to a medical professional, in contrast to prescription only medicines (POM). ... A dissociative is a drug which reduces (or blocks) signals to the conscious mind from other parts of the brain, typically, but not necessarily, or limited to the physical senses. ... Hallucinogenic drugs or hallucinogens are drugs that can alter sensory perceptions, elicit alternate states of consciousness, or cause hallucinations. ... Ketamine is a dissociative anesthetic for use in human and veterinary medicine developed by Parke-Davis (1962). ... Phencyclidine (a contraction of the chemical name phenylcyclohexylpiperidine), abbreviated PCP, is a dissociative drug formerly used as an anesthetic agent, exhibiting hallucinogenic and neurotoxic effects. ...

References

Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 197th day of the year (198th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 197th day of the year (198th in leap years) in the Gregorian calendar. ... is the 187th day of the year (188th in leap years) in the Gregorian calendar. ... Year 2004 (MMIV) was a leap year starting on Thursday of the Gregorian calendar. ... is the 209th day of the year (210th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ...

See also

• Methorphan
• Levomethorphan
• Dissociatives
  • PCP
  • Ketamine
  • Nitrous oxide
  • Salvia divinorum
• Psychoactive drug