The nonnarcotic antitussive drug dimemorfan: a review.
The antitussive dimemorfan phosphate was discovered through extensive screening of morphinic derivatives and was introduced in Japan in 1975. The majority of studies on dimemorfan have been published in Japanese, and this review aims to make these data more generally available. The antitussive action of dimemorfan appears to be directly on the cough center in the medulla. Dimemorfan does not induce any significant physical or psychologic dependence, and its antitussive action is not affected by the opioid-receptor blocker levallorphan. Dimemorfan is therefore considered a nonnarcotic antitussive. Studies of antitussive effects in animal models indicate that dimemorfan is up to three times more potent than codeine and is equivalent to dextromethorphan. Three major comparative clinical trials and postmarketing surveillance studies showed that dimemorfan is equally or slightly more efficacious than dextromethorphan, benproperine phosphate, or placebo for the control of coughing. Several animal and clinical studies have confirmed the efficacy and safety of dimemorfan. Dimemorfan was effective in the majority of patients. In contrast to the narcotic antitussives, dimemorfan caused no serious problems with the digestive system, such as constipation and disorders of the bile duct, caused no dependence or tolerance, and was unlikely to have clinical analgesic effects. Minor side effects, such as loss of appetite, nausea, and drowsiness, were seen in less than 10% of patients. A syrup formulation of dimemorphan that retains its efficacy and safety is also available. Overall, these data indicate that dimemorfan is an effective nonnarcotic antitussive agent with a low incidence of adverse events.
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Applied Pharmacology Research Pharmacology Laboratory, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tokyo, Japan.
D000818:Animals; D000996:Antitussive Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003371:Cough / Q000188:drug therapy*; D006801:Humans; D007928:Lethal Dose 50; D009019:Morphinans / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*
D000996:Antitussive Agents; D009019:Morphinans; C012621:dimemorfan