Dextromethorphan availability

A -methyl-D-aspartate antagonists Dextromethorphan Limited number of drugs in this class are available for human use. Study findings have been negative. 

The opioid derivatives most commonly used as antitussives are dextromethorphan, codeine, levopropoxyphene, and noscapine (levopropoxyphene and noscapine are not available in the USA). They should be used with caution in patients taking monoamine oxidase inhibitors (see Table 31-5). Antitussive preparations usually also contain expectorants to thin and liquefy respiratory secretions. Importantly, due to increasing reports of death in young children taking dextromethorphan in formulations of over-the-counter "cold/cough" medications, its use in children less than 6 years of age has been banned by the FDA. Moreover, due to variations in the metabolism of codeine, its use for any purpose in young children is being reconsidered. 

Dextromethorphan is the dextrorotatory stereoisomer of a methylated derivative of levorphanol. It is purported to be free of addictive properties and produces less constipation than codeine. The usual antitussive dose is 15-30 mg three or four times daily. It is available in many over-the-counter products. Dextromethorphan has also been found to enhance the analgesic action of morphine and presumably other -receptor agonists. However, abuse of its purified (powdered) form has been reported to lead to serious adverse events including death. 

For each drug, the prevalence of abuse was partly attributable to its absolute availability — for example, the over-the-counter status of dextromethorphan (DXM) or the expansion of fentanyl and butorphanol from inpatient to outpatient use. But the pattern of abuse for each drug was distinctive and probably could not have been predicted from the available experimental abuse-liability data. 

Dextromethorphan is available without a prescription in the United States. However, most patients receive special instmctions from their physician on how to use this medication properly. 

There is increasing concern over the street abuse of dextromethorphan, which is available in a variety of products. There have been a few reports of abuse and a handful of case reports of overdose and death. Nevertheless, dextromethorphan was specifically left out of the Controlled Substances Act (CSA) of 1970 and has not been added to the Drug Enforcement Administration (DEA) scheduling process despite these reports. This decision was made because dextromethorphan is not considered a narcotic and is generally thought to have a low addiction potential. However, the DEA is monitoring dextromethorphan and may add it to its list of controlled substances at some point in the future. 

Hydrogenation of the enamide 86 with a Ru catalyst and MeOBIPHEP 31 gives a feasible approach to the antitussive agent dextromethorphan (89) (Scheme 26). The readily available imine substrate 87 is hydrogenated using an Ir catalyst with the ferrocenyl diphosphine 88, albeit with a relatively low substrate/catalyst molar ratio of 1500 and an ee of 89% [20]. 

Dextromethorphan (DXM)," streetdrugs.org, Publishers Group LLC. December 2006. Available online. URL http // www.streetdrugs.org/dxm.htm. 

Kappa receptor activation does not appear to be responsible for dependence, euphoria, or effects on smooth muscle. Increases in cerebral blood flow and (possibly) increased intracranial pressure result from the respiratory depressant actions of opioid analgesics. The latter effects are due to increased arterial PrOj, which results from mu receptor inhibition of the medullary respiratory center. However, the activation of kappa receptors contributes to analgesia at the spinal level and is probably responsible for sedative actions of the opioids. The answer is (D). Codeine and possibly nalbuphine could decrease gastrointestinal peristalsis but not without marked side effects (and a prescription). Dextromethorphan is a cough suppressant. The other two drugs listed are opioids with antidiarrheal actions. Diphenoxylate is not available over-the-counter since it is a constituent of a proprietary combination that includes atropine sulfate (Lomotil). Loperamide is available over-the-counter. The answer is (D). 

Dextromethorphan, an effective antitussive drug, is the dextrorotatory stereoisomer of a derivative of levorphanol. The drug is available without a prescription and is the active component in many over-the-counter cough suppressants. Dextromethorphan has no appreciable analgesic activity and minimal abuse liability. In comparison with codeine—also an effective antitussive—dextromethorphan causes less constipation. The answer is (D). 

Popik, P., Kozela, E and Danysz, W. (2000). Clinically available NMDA receptor antagonists memantine and dextromethorphan reverse existing tolerance to the antinociceptive effects of morphine in mice. Naunyn-Sehmied. Arch Pharmacol. 361,... 

Dextromethorphan HBr is the ( + )-isomer of the 3-methoxy form of the synthetic opioid levorphanol. It lacks the analgesic, respiratory depressant, and abuse potential of p opioid agonists but retains the centrally acting antitussive action. Dextromethorphan is not an opioid and is not listed in the Controlled Substances Act. Its effectiveness as an antitussive is less than that of codeine. Dextromethorphan is available in a number of nonprescription cough formulations. 

Other nonnarcotic preparations include noscapine and levopropoxyphene, although their antitussive efficacy has not been proven. Levodropropizine, a nonopioid antitussive with peripheral inhibition of sensory cough receptors, has a favorable benefit-risk profile compared with dextromethorphan (Catena and Daffonchio 1997) this is currently available in several European countries. 

A. Specific levels. Assays exist for semm and urine analysis, but are not generally available. In seven fatal infant cases, blood levels averaged 0.38 mg/L (range 0.10-0.95). Despite its stmctural similarity to opioids, dextromethorphan is not likely to produce a false-positive urine opioid immunoassay screen. However, it may produce a false-positive result on methadone and phencyclidine immunoassays. Dextromethorphan is readily detected by comprehensive urine toxicology screening. 

Despite the very limited information available, the severity of the reactions indicates that patients taking MAOIs should avoid taking dextromethorphan. The manufacturer of moclobemide also contraindicates the concurrent use of dextromethorphan. Patients should be warned that many cough preparations contain dextromethorphan. 

Dextromethorphan is available in different forms such as capsule, liquid, liquid gelatin capsule, lozenge, tablets, intramuscular, as well as in powdered forms (available on the internet). 

Structure. The availability of (+)-dihydrothebainone, later accomplished with better procedures (lijima et al. 1978a), made it possible to investigate several unnatural (+)-opioids as neurochemical tools (Jacquet et al. 1977, lijima et al. 1978b). It is interesting to note that sinomenine, only recently tested in an antitussive screen (Nakamura personal communication) proved superior to dextromethorphan and codeine, suggesting that antitussive agents may still be discovered in the (+)-series of mor-phinan alkaloids (Kerekes et al. in press). 

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