| Identification | More | [Name]
DEXTROMETHORPHAN | [CAS]
125-71-3 | [Synonyms]
DEXTROMETHORPHAN
13-alpha,14-alpha-morphinan,3-methoxy-17-methyl-9-alph
13alpha,14alpha-morphinan,3-methoxy-17-methyl-9alph
3-methoxy-17-methyl-,(9-alpha,13-alpha,14-alpha)-morphina
3-Methoxy-17-methyl-9alpha,13alpha,14alpha-morphinan
3-Methoxy-17-methyl-9alpha,13alpha-morphinan
3-Methoxy-17-methylmorphinan
9alpha,13alpha,14alpha-Morphinan, 3-methoxy-17-methyl-
Ba 2666
ba2666
delta-Methorphan
Dextromethorfan
Dextrometorphan
D-methorphan
Methorphan
Morphinan, 3-methoxy-17-methyl-, (9alpha,13alpha,14alpha)-
Racemethorphan [as d-form]
(+)-3-methoxy-N-methylmorphinan
(+)-cis-1,3,4,9,10,10a-hexahydro-6-methoxy-11-methyl-2H-10,4a-iminoethanophenanthrene
Benylin DM | [EINECS(EC#)]
204-752-2 | [Molecular Formula]
C18H25NO | [MDL Number]
MFCD00866833 | [Molecular Weight]
271.4 | [MOL File]
125-71-3.mol |
| Hazard Information | Back Directory | [Description]
Dextromethorphan is an over-the-counter drug that is sold alone and in combination with other products as a cough suppressant for children and adults. We have previously recommended dextromethorphan as a safe and effective cough suppressant for both children and adults. However, the weight of the evidence now suggests that dextromethorphan is no more effective than an inactive placebo syrup in suppressing a nighttime cough in children. It is the disomer of the potent opiate analgesic 3-methoxyN-methylmorphine (levorphanol). Although dextromethorphan is structurally related to opioids, it is devoid of analgesic or sedative effects at therapeutic doses. Dextromethorphan is metabolized by CYP2D6 to a more potent metabolite, dextrorphan. Dextrorphan is a stronger noncompetitive antagonist than dextromethorphan for the N-methyl-D-aspartate (NMDA) glutamate receptor.These properties promote its use in treatment of neuropathic and postoperative pain management. | [Chemical Properties]
Dextromethorphan is a white to slightly yellow, odorless, crystalline powder. The hydrobromide salt of dextromethorphan occurs as white crystals or a white crystalline powder, soluble in water, alcohol, and chloroform. It acts upon the central nervous system to suppress the cough reflex. | [Uses]
Antitussive. | [Uses]
Dextromethorphan is used therapeutically as an over-thecounter
cough suppressant and antitussive. It is also commonly
abused particularly by adolescents because of its relative ease of
availability. | [Definition]
ChEBI: An organic heterotetracyclic compound that is morphinan substituted by a methoxy group at position 3 and a methyl group at position 7. It is used as an antitussive drug for suppressing cough. | [Indications]
This drug possesses a pronounced anticough effect and minimal action on the CNS. It is
not addictive. | [Brand name]
Benylin DM
(Parke-Davis); Dextromethorphan Hydrobromide OROS
Tablets (Ciba-Geigy); Drixoral Cough (Schering-Plough HealthCare); PediaCare 1 (McNeil Consumer); Romilar
(Hoffmann-LaRoche-International); St. Joseph Cough Syrup
(Schering-Plough HealthCare);Agrippol;Dextophan;Dextrophen. | [Biological Functions]
Dextromethorphan hydrobromide is the D-isomer of
levorphanol. It lacks CNS activity but acts at the cough
center in the medulla to produce an antitussive effect. It
is half as potent as codeine as an antitussive. Anecdotal
reports of abuse exist, but studies of abuse potential are
lacking. It has few side effects but does potentiate the
activity of monoamine oxidase inhibitors, leading to hypotension
and infrequently coma. Dextromethorphan is
often combined in lozenges with the local anesthetic
benzocaine, which blocks pain from throat irritation
due to coughing. | [Synthesis Reference(s)]
The Journal of Organic Chemistry, 30, p. 1769, 1965 DOI: 10.1021/jo01017a014 | [General Description]
Dextromethorphan is the dextrorotatory form of levorphanolwith a methoxy group on the 3-position. It is availablein more than 140 over-the-counter (OTC) cough and coldformulations. Evidence-based reviews have been unable toconclude that it is more effective than placebo in reducingcough. Like (+) and (-) levorphanol, (+) dextromethorphanis a potent NMDA antagonist and, in higher than recommendeddoses, has the potential for causing dissociativeanesthetic effects similar to ketamine or phencyclidine (PCP).The OTC status and availability of pure dextromethorphanpowder online has contributed greatly to its abuse in recentyears. DAWN reports that in 2004, there were approximately12,500 emergency room visits involving dextromethorphanwith 44% of those involving abuse of the drug. The 2006National Survey on Drug Abuse report shows that nearly 1million persons aged 12 to 25 years (1.7%) misused OTCcough and cold medications in the past year.
Dextromethorphan’s ability to antagonize the NMDA receptorhas led to its use to treat phantom pain, diabetic neuropathy,and postoperative acute pain. | [Pharmacokinetics]
Dextromethorphan is absorbed rapidly from the GI tract, with antitussive activity occurring within 15 to 30 minutes. It undergoes extensive hepatic metabolism. Excretion is mainly renal, with some drug eliminated unchanged but most eliminated as metabolites. Dextromethorphan is related chemically to the opiate agonists and can suppress coughing as effectively as narcotics. Cough suppression occurs by several mechanisms, but mainly the drug directly affects the cough center in the medulla. Therapeutic doses do not affect ciliary activity. | [Side effects]
Although adverse effects are generally rare, dextromethorphan toxicity can occur and is characterized by nausea and vomiting, drowsiness, dizziness, irritability, and restlessness. In excessive doses, dextromethorphan poisoning may occur and induce symptoms similar to those associated with phencyclidine. | [Safety]
Despite the safety of dextromethorphan when used at the recommended dosage (<120 mg/day), higher doses can result in nausea, vomiting, seizure, loss of consciousness, irregular heartbeat, and death. Serotonin syndrome may develop in patients on other serotonergic drugs, due to additive inhibition of serotonin reuptake by dextromethorphan. Patients with genetic variations in CYP2D6, causing rapid metabolism of dextromethorphan, may present with greater clinical effects. | [Synthesis]
Dextromethorphan, (9|á,13|á,14|á)-3-methoxy-17-methylmorphinane
(23.2.1), is synthesized from ()-3-hydroxy-N-methylmorphinane by methylating the phenol
hydroxyl group using phenyltrimethylammonium chloride and sodium methoxide in
methanol. The resulting racemic product ()-3-methoxy-N-methylmorphinane is separated
into isomers using D-tartaric acid, which produces dextromethor-phan.
| [Environmental Fate]
Dextromethorphan is the D-isomer of the codeine analog,
methorphan. Unlike the L-isomer, it has no analgesic or
addictive properties and does not act through the opioid
receptors. The exact mechanism for the antitussive effect by
dextromethorphan remains unclear and is likely multifactorial.
Dextromethorphan is known to be an N-methyl-D-aspartate
(NMDA) receptor antagonist; however, dextromethorphan
binding sites are not limited to the known distribution of
NMDA receptors.
Dextromethorphan’s main metabolite, dextrorphan, has
NMDA receptor antagonist properties similar to ketamine and
phencyclidine. This NMDA receptor antagonism is believed to
result in a decreased reuptake of catecholamines. Dextromethorphan
also inhibits the reuptake of serotonin. These
properties make dextromethorphan have a high abuse and
misuse potential.
Dextromethorphan is a common ingredient in over-thecounter
cough and cold preparations, and is often combined
with other agents including concurrent antihistamines,
decongestants, analgesics, and ethanol. Patients may exhibit
toxicity due to these coingestants. |
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