125-71-3 Usage
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
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.
Indications
Dextromethorphan is used in treating nonproductive cough. It is available widely in a variety of nonprescription forms, such as capsules, lozenges, syrups, extended-release oral suspension, and chewable tablets. This drug possesses a pronounced anticough effect and minimal action on the CNS. It is not addictive.
Definition
ChEBI: Dextromethorphan is a 6-methoxy-11-methyl-1,3,4,9,10,10a-hexahydro-2H-10,4a-(epiminoethano)phenanthrene in which the sterocenters at positions 4a, 10 and 10a have S-configuration. It is a prodrug of dextrorphan and used as an antitussive drug for suppressing cough. It has a role as a NMDA receptor antagonist, a neurotoxin, a xenobiotic, an environmental contaminant, an antitussive, a prodrug and a oneirogen. It is functionally related to a dextrorphan. It is an enantiomer of a levomethorphan.
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, (9α,13α,14α)-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.
Check Digit Verification of cas no
The CAS Registry Mumber 125-71-3 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 1,2 and 5 respectively; the second part has 2 digits, 7 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 125-71:
(5*1)+(4*2)+(3*5)+(2*7)+(1*1)=43
43 % 10 = 3
So 125-71-3 is a valid CAS Registry Number.
InChI:InChI=1/C18H25NO/c1-19-10-9-18-8-4-3-5-15(18)17(19)11-13-6-7-14(20-2)12-16(13)18/h6-7,12,15,17H,3-5,8-11H2,1-2H3/t15-,17+,18+/m1/s1
125-71-3Relevant articles and documents
Synthesis, in vitro and in vivo studies, and molecular modeling of N-alkylated dextromethorphan derivatives as non-competitive inhibitors of α3β4 nicotinic acetylcholine receptor
Jozwiak, Krzysztof,Targowska-Duda, Katarzyna M.,Kaczor, Agnieszka A.,Kozak, Joanna,Ligeza, Agnieszka,Szacon, Elzbieta,Wrobel, Tomasz M.,Budzynska, Barbara,Biala, Grazyna,Fornal, Emilia,Poso, Antti,Wainer, Irving W.,Matosiuk, Dariusz
, p. 6846 - 6856 (2014)
9 N-alkylated derivatives of dextromethorphan are synthesized and studied as non-competitive inhibitors of α3β4 nicotinic acetylcholine receptors (nAChRs). In vitro activity towards α3β4 nicotinic acetylcholine receptor is determined using a patch-clamp technique and is in the micromolar range. Homology modeling, molecular docking and molecular dynamics of ligand-receptor complexes in POPC membrane are used to find the mode of interactions of N-alkylated dextromethorphan derivatives with α3β4 nAChR. The compounds, similarly as dextromethorphan, interact with the middle portion of α3β4 nAChR ion channel. Finally, behavioral tests confirmed potential application of the studied compounds for the treatment of addiction.
A process for preparing dextromethorphan method
-
Paragraph 0177; 0186; 0187; 0194, (2018/02/04)
The invention relates to a novel method for preparing dextromethorphan. When the method is used for preparing an intermediate (+)-1-(4-methoxy) benzyl-1,2,3,4,5,6,7,8-hexahydroisoquinoline (VI), a catalytic reducing method is adopted to carry out chiral reduction on 1-(4-methoxy) benzyl-3,4,5,6,7,8-hexahydroisoquinoline (VI), so that the intermediate is prepared with high selectivity. The novel method disclosed by the invention can cancel complex operations such as chiral resolution, is simple to operate, gentle in reaction condition, short in total time, wide in material source, and very suitable for industrially producing dextromethorphan.
Nickel-Catalyzed Cross-Coupling of Anisoles with Alkyl Grignard Reagents via C-O Bond Cleavage
Tobisu, Mamoru,Takahira, Tsuyoshi,Chatani, Naoto
supporting information, p. 4352 - 4355 (2015/09/15)
Nickel-catalyzed cross-coupling of methoxyarenes with alkyl Grignard reagents, which involves the cleavage of the C(aryl)-OMe bond, has been developed. The use of 1,3-dicyclohexylimidazol-2-ylidene as a ligand allows the introduction of a variety of alkyl groups, including Me, Me3SiCH2, ArCH2, adamantyl, and cyclopropyl. The method can also be used for the alkylative elaboration of complex molecules bearing a C(aryl)-OMe bond.
