Dextromethorphan
Systematic (IUPAC) name
((+)-3-methoxy-17-methyl-(9α,13α,14α)-morphinan)
Identifiers
CAS number	125-71-3
ATC code	R05DA09
PubChem	5360696
DrugBank	APRD00655
Chemical data
Formula	C18H25NO
Mol. mass	271. IUPAC Nomenclature is a system of naming Chemical compounds and of describing the science of Chemistry in general CAS registry numbers are unique numerical identifiers for Chemical compounds Polymers biological sequences mixtures and Alloys They are also referred to The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug A section of the Anatomical Therapeutic Chemical Classification System. PubChem is a Database of chemical Molecules The system is maintained by the National Center for Biotechnology Information (NCBI a component The DrugBank database available at the University of Alberta is a unique Bioinformatics and Cheminformatics resource that combines detailed drug (i A chemical formula is a way of expressing information about the Atoms that constitute a particular Chemical compound, and how the relationship between those atoms changes Carbon (kɑɹbən is a Chemical element with the symbol C and its Atomic number is 6 Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1 Nitrogen (ˈnaɪtɹəʤɪn is a Chemical element that has the symbol N and Atomic number 7 and Atomic weight 14 Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one 4 g/mol
SMILES	eMolecules & PubChem
Physical data
Melt. point	111 °C (232 °F)
Pharmacokinetic data
Bioavailability	11%[1]
Metabolism	Hepatic (liver) enzymes: major CYP2D6, minor CYP3A4, and minor CYP3A5
Half life	1. The melting point of a solid is the temperature range at which it changes state from solid to Liquid. In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems 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 Cytochrome P450 3A4 (abbreviated CYP3A4) ( a member of the Cytochrome P450 mixed-function oxidase system is one of the most important enzymes involved in the metabolism Cytochrome P450 family 3 subfamily A polypeptide 5, also known as CYP3A5, is a human Gene. The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity 4–3. 9 hours
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	A(AU) C(US)
Legal status	Pharmacy Only (S2)(AU) OTC(US)
Routes	Oral

Dextromethorphan (DXM or DM) is an antitussive (cough suppressant) drug found in many over-the-counter cold and cough medicines. Excretion is the process of eliminating waste products of Metabolism and other non-useful materials The kidneys are complicated organs that have numerous biological roles The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical if it is used as directed by the mother during For a topic outline on this subject see List of basic Australia topics. The United States of America —commonly referred to as the The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction The Standard for the Uniform Scheduling of Drugs and Poisons, abbreviated SUSDP, is a document used in the regulation of drugs and poisons in Australia. For a topic outline on this subject see List of basic Australia topics. Over-the-counter (OTC drugs are medicines that may be sold without a prescription, in contrast to Prescription drugs The name "over-the-counter" The United States of America —commonly referred to as the In Pharmacology and Toxicology, a route A cough medicine is a medicinal 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 The name "over-the-counter" Acute viral nasopharyngitis or acute coryza, usually known as the common cold, is a highly contagious viral Infectious disease of the A cough medicine is a medicinal drug used to treat Coughing and related conditions 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. A throat lozenge or cough drop is a small medicated Candy intended to be dissolved slowly in the mouth to lubricate and soothe irritated tissues of the Throat In the GNU Compiler Collection, GENERIC is an intermediate representation common to all the front-ends of GCC

When taken at doses higher than are medically recommended, dextromethorphan acts as a dissociative hallucinogenic drug. A dissociative is a drug which reduces (or blocks signals to the conscious mind from other parts of the brain typically but not necessarily limited to the Senses Such The general group of pharmacological agents commonly known as hallucinogens can be divided into three broad categories Psychedelics, Dissociatives 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. Neurochemistry is the branch of Neuroscience devoted to the study of Neurochemicals A neurochemical is an organic molecule that participates in neural activity NMDA receptor antagonists are a class of Anesthetics that work to antagonize, or inhibit the action of the N-methyl d-aspartate receptor ( NMDAR Ketamine is a drug for use in human and veterinary medicine developed by Parke-Davis (today a part of Pfizer) in 1962 Phencyclidine (a complex clip of the chemical name phenylcyclohexylpiperidine, commonly initialised as PCP) is a Dissociative drug ^[3]

Chemistry

Dextromethorphan is the dextrorotatory enantiomer of the methyl ether of levorphanol, a narcotic analgesic. Dextrorotation and levorotation (also spelled laevorotation) refer respectively to the properties of rotating plane Polarized light clockwise (for dextrorotation In Chemistry, an enantiomer ( from the Greek ἐνάντιος opposite and μέρος part or portion is one of two Stereoisomers that are nonsuperimposable Ether is a class of Organic compounds which contain an ether group — an Oxygen Atom connected to two (substituted Alkyl Levorphanol (Levo-Dromoran is an Opioid medication used to treat severe pain It is also a stereoisomer of levomethorphan, an opioid analgesic. Stereoisomers are isomeric molecules that have the same molecular formula and sequence of bonded atoms (constitution but which differ in the three dimensional orientations Levomethorphan is the l- Stereoisomer of Methorphan. The effects of the two isomers are quite different An opioid is a chemical Substance that has a Morphine -like action in the body It is named according to IUPAC rules as (+)-3-methoxy-17-methyl-9α,13α,14α-morphinan. The International Union of Pure and Applied Chemistry ( IUPAC) (aɪjuːpæk or ay-yoo-pec) is an international Non-governmental organization Morphinan is the base chemical structure of a subgroup of Opioids It is also an alternative name for the drug Dromoran, which is a racaemic parent drug of Levo-Dromoran® 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. Chloroform, also known as trichloromethane and methyl trichloride, is a Chemical compound with formula C[[Hydrogen H]] Cl Water is a common Chemical substance that is essential for the survival of all known forms of Life. 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. Sodium polystyrene sulfonate (or polystyrene sulfonic acid) is a type of Polymer and Ionomer based on Polystyrene. Dextromethorphan's specific rotation in water is +27. The specific rotation of a Chemical compound is defined as the observed angle of Optical rotation α when plane-polarized light is passed through a sample with a 6° (20°C, Sodium D-line).

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. 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 Maladie de Charcot, or in the United States Lou Gehrig's Disease) is a progressive Multiple sclerosis (abbreviated MS also known as disseminated sclerosis or encephalomyelitis disseminata) is an autoimmune condition in which the ^[4] Dextromethorphan is also being investigated as a possible treatment for neuropathic pain and pain associated with fibromyalgia. Neuropathy is a medical term usually short for Peripheral neuropathy. Fibromyalgia (FM is a disorder classified by the presence of chronic widespread Pain and tactile Allodynia. ^[5]

Pharmacokinetics

At therapeutic doses, dextromethorphan acts centrally (meaning that it acts on the brain) as opposed to locally (on the respiratory tract). In Vertebrates the central nervous system ( CNS) is the part of the Nervous system which is enclosed in the Meninges. The brain is the center of the Nervous system in animals All Vertebrates and the majority of Invertebrates have a brain In humans the respiratory tract is the part of the Anatomy that has to do with the process of respiration. It elevates the threshold for coughing, without inhibiting ciliary activity. A cilium (plural cilia) is an Organelle found in eukaryotic cells Cilia are tail-like projections extending approximately Dextromethorphan is rapidly absorbed from the gastrointestinal tract and converted into an active metabolite, dextrorphan, within 15 to 60 minutes of ingestion. A prodrug is a pharmacological substance ( drug) that is administered in an inactive (or significantly less active form Dextrorphan (DXO is a pharmacologically active metabolite of Dextromethorphan (DXM 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.

Because administration of dextromethorphan can trigger a histamine release (an allergic reaction), its use in atopic children is very limited. Histamine is a Biogenic amine involved in local immune responses as well as regulating physiological function in the gut and acting as a Neurotransmitter Allergy is a disorder of the Immune system often also referred to as Atopy. Atopy (/ˈætəpi/ Greek ἀτοπία - placelessness or atopic syndrome is an allergic Hypersensitivity affecting parts of the body

Side-effects

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

body rash/itching nausea drowsiness dizziness

excitation vomiting blurred vision dilated pupils

sweating fever hypertension

shallow respiration diarrhea urinary retention

Can also cause increases in:

heart rate

blood pressure

body temperature

Dextromethorphan can also cause other gastrointestinal disturbances. A rash is a change of the Skin which affects its color appearance or Texture. Itch ( Latin: pruritus) is an unpleasant Sensation that evokes the desire or Reflex to scratch Nausea ( Latin: Nausea, Greek:, " Sea-sickness " also called wamble) is the sensation of unease and discomfort Somnolence (or " drowsiness " is a state of near- Sleep, a strong desire for sleep or sleeping for unusually long periods (c Many different terms are often used to describe what is collectively known as dizziness. Excitation or excitement can refer to The Excited state of an atom The Excitation (magnetic provided with an electrical Vomiting (also called throwing up, emesis) is the forceful expulsion of the contents of one's Stomach through the Mouth and sometimes the "Dilated pupil" redirects here An Eye examination sometimes requires the dilation of the pupil Fever (also known as pyrexia, from the Greek pyretos meaning fire or a febrile response, from the Latin word Febris Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the Blood pressure is chronically elevated In living organisms a respiratory system functions to allow Gas exchange. In Medicine, diarrhea, also spelled diarrhoea (see spelling differences) is frequent loose or liquid Bowel movements Acute diarrhea Urinary retention also known as ischuria is a lack of ability to Urinate. Measuring heart rate The Pulse rate (which in most people is identical to the heart rate can be measured at any point on the body where an Artery 's pulsation Blood pressure is also the title of a short story by Damon Runyan in Guys and Dolls and Other Stories Core temperature, also called core body temperature, is the operating Temperature of an Organism, specifically in deep structures of the body such as the When injected directly into the blood stream, some studies suggest that dextromethorphan has the potential to cause Olney's Lesions. Olney's lesions, also known as NMDA receptor antagonist Neurotoxicity (NAN are a form of Brain damage caused by high Doses of Dissociative ^[7][8] In some rare documented cases, dextromethorphan has produced psychological dependence in people who abused it. The term " addiction " is used in many contexts to describe an obsession compulsion or excessive Physical dependence or psychological dependence such as However, it does not produce physical addiction, according to the WHO Committee on Drug Dependence. The term " addiction " is used in many contexts to describe an obsession compulsion or excessive Physical dependence or psychological dependence such as

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. Monoamine oxidase inhibitors ( MAOIs) are a class of powerful antidepressant drugs prescribed for the treatment of depression. Selective serotonin reuptake inhibitors ( SSRIs) are a class of Antidepressants used in the treatment of depression, Anxiety disorders Depressant is a chemical agent that diminishes the function or activity of a specific part of the body (see also Sedative) A histamine antagonist is an agent which serves to inhibit the release or action of Histamine. A psychoactive drug or psychotropic substance is a Chemical substance that acts primarily upon the Central nervous system where it alters Brain ^[6]

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. Atopy (/ˈætəpi/ Greek ἀτοπία - placelessness or atopic syndrome is an allergic Hypersensitivity affecting parts of the body ^[6]

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 blood-brain barrier (BBB is a metabolic or cellular structure in the Central nervous system (CNS that restricts the passage of various chemical substances and microscopic 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. Metabolomics is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind" - specifically the study of their small-molecule metabolite Dextrorphan (DXO is a pharmacologically active metabolite of Dextromethorphan (DXM 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. Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins 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. Urine is a liquid waste product of the body secreted by the Kidneys by a process of filtration from Blood and Excreted through the Urethra. ^[6]

A major metabolic catalyst involved is the cytochrome P450 enzyme known as 2D6, or CYP2D6. Cytochrome P450 (abbreviated CYP, P450, infrequently CYP450) is a very large and diverse superfamily of Hemoproteins found in all Domains Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins 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 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. In Biochemistry, a metabolic pathway is a series of chemical reactions occurring within a cell. ^[9]

A large number of medications (including antidepressants) are potent inhibitors of CYP2D6. An antidepressant is a Psychiatric medication used for alleviating major 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 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:

• NMDA receptor antagonist
• σ₁ and σ₂ receptor agonist. The blood-brain barrier (BBB is a metabolic or cellular structure in the Central nervous system (CNS that restricts the passage of various chemical substances and microscopic NMDA receptor antagonists are a class of Anesthetics that work to antagonize, or inhibit the action of the N-methyl d-aspartate receptor ( NMDAR The sigma-1 receptor is a Transmembrane protein expressed in many different tissue types The sigma receptors σ1 and σ2 are receptors which bind to Ligands such as 4-PPBP, SA 4503, Ditolylguanidine ^[10]
• α3β4 nicotinic receptor antagonist^[11]
• Serotonin reuptake inhibitor^[12]
• Dopamine reuptake inhibitor (disputed)^[6][13]
• NADPH inhibitor ^[14]

Brand names

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

Acodin Askorex Benylin BRONCORIDE-DM Buckley's Coricidin

Creomulsion Delsym Daro Kafosed Mucinex DM

Sucrets, Cough Resilar Robitussin TEXCOL-DM Triaminic Tussal

Tussi12 D & DS Tussidex Vicks Zicam Cough Plus D

History

Dextromethorphan was first patented under U.S. Patent 2,676,177 . Structure Nicotinic receptors with a molecular mass of 290 kDa, are made up of five subunits arranged symmetrically around the central pore. Selective serotonin reuptake inhibitors ( SSRIs) are a class of Antidepressants used in the treatment of depression, Anxiety disorders Dopamine Reuptake Inhibitors ( DARI) Dopamine Uptake Inhibitors, Dopamine Transporter Inhibitors are compounds that inhibit the Reuptake of extracellular Benylin is a Brand name owned by Johnson and Johnson for a range of cough cold and flu medications WK Buckley Limited is a Canadian Corporation founded in 1920 by W Coricidin, Coricidin 'D' (decongestant or CoricidinHBP (for h igh b lood p ressure is the name of a drug marketed by Schering-Plough 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. Vicks is a line of over-the-counter Medications owned by the American company Procter & Gamble. The FDA approved dextromethorphan for over-the-counter sale as a cough suppressant in 1958. Over-the-counter (OTC drugs are medicines that may be sold without a prescription, in contrast to Prescription drugs The name "over-the-counter" 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). Codeine ( INN) or methylmorphine is an Opiate used for its Analgesic, antitussive and antidiarrheal properties ^[15] As with most cough suppressants, studies show that dextromethorphan's effectiveness is highly debatable,^[16] especially in children. A cough medicine is a medicinal drug used to treat Coughing and related conditions ^[17]

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. A cough medicine is a medicinal drug used to treat Coughing and related conditions ^[15]

More recently (the early 1990s) gel capsule forms began reappearing in the form of Drixoral Cough Liquid Caps and later 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. See Dextromethorphan for info on the medical use of DXM and its chemical pharmacological and other misc information Over-the-counter (OTC drugs are medicines that may be sold without a prescription, in contrast to Prescription drugs The name "over-the-counter" ^[15] 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). A dissociative is a drug which reduces (or blocks signals to the conscious mind from other parts of the brain typically but not necessarily limited to the Senses Such The general group of pharmacological agents commonly known as hallucinogens can be divided into three broad categories Psychedelics, Dissociatives Ketamine is a drug for use in human and veterinary medicine developed by Parke-Davis (today a part of Pfizer) in 1962 Phencyclidine (a complex clip of the chemical name phenylcyclohexylpiperidine, commonly initialised as PCP) is a Dissociative drug

References

See also

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

Methorphan comes in two forms Dextromethorphan - An over-the-counter cough suppressant Levomethorphan - The left hand isomer of the above Levomethorphan is the l- Stereoisomer of Methorphan. The effects of the two isomers are quite different A dissociative is a drug which reduces (or blocks signals to the conscious mind from other parts of the brain typically but not necessarily limited to the Senses Such Phencyclidine (a complex clip of the chemical name phenylcyclohexylpiperidine, commonly initialised as PCP) is a Dissociative drug Ketamine is a drug for use in human and veterinary medicine developed by Parke-Davis (today a part of Pfizer) in 1962 Nitrous oxide, commonly known as " laughing gas," is a Chemical compound with the Chemical formula N 2 O. Salvia divinorum, also known as Diviner’s Sage, ska María Pastora, Sage of the Seers, or simply by the genus name A psychoactive drug or psychotropic substance is a Chemical substance that acts primarily upon the Central nervous system where it alters Brain

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