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| Toxicity Summary |
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| Link to the Distributed Structure-Searchable Toxicity (DSSTox) Database |
| IDENTIFICATION AND USE: Dextromethorphan is a white odorless solid crystal or powder. It is an opium alkaloid derivative, which is found in cough and cold preparations. HUMAN STUDIES: Dextromethorphan is a drug of abuse. The main risks associated with dextromethorphan are ataxia, central nervous system (CNS) stimulation, dizziness, lethargy and psychotic behavior. Less frequently with large doses seizures and respiratory depression can occur. Nausea, vomiting, constipation and tachycardia may also occur. CNS effects include ataxia, drowsiness, vertigo and rarely coma. CNS stimulation may be observed. Restlessness, increased muscle tone with body rigidity have been reported. With extremely large ingestions respiratory depression can occur. Gastrointestinal effects include nausea, vomiting, constipation and dry mouth. Urinary retention may be seen. Dextromethorphan abuse has been described and produces euphoria, CNS stimulation, visual and/or auditory hallucinations. Dextromethorphan hydrobromide is the drug form, thus the possibility of bromide poisoning should be considered in the long term abuser. Dextromethorphan enhances serotonin activity by inhibiting the reuptake of serotonin. Specific non-opioid dextromethorphan binding sites are present in the CNS which mediate the antitussive effects, separate from codeine and other opioids. Death has been reported after overdose in two cases but quantity was uncertain. In adults, it can cause intoxication with hyperexcitability, visual and/or auditory hallucinations. It has been reported that sniffing two to three times a day over 2 to 3 months produced euphoria and restlessness for up to 2 hours followed by dizziness, nausea, depression and fatigue. Toxicity may be variable in children. Some children have shown no symptoms while others have shown ataxia, stupor, transient fever, lethargy or nystagmus. Seizures have also been reported. Long-acting products may be more toxic in children, producing prolonged CNS depression. There was no association between dextromethorphan and malformations. Dextromethorphan is generally considered safe to use during pregnancy. Urticaria was reported in a child after acute overdose of a long-acting preparation. A cutaneous lesion consistent with a fixed-drug reaction was reported after ingestion over 2 to 3 weeks in therapeutic doses. ANIMAL STUDIES: Dextromethorphan is a weak noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. It is metabolized in vivo to dextrorphan, a more potent noncompetitive NMDA antagonist that is the dextrorotatory enantiomer of the opioid agonist levorphanol. Although in rats both dextromethorphan and dextrorphan increased plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone, the dextromethorphan-induced responses occurred more rapidly than the dextrorphan-induced responses. Three sets of zebrafish embryos/larvae were exposed to dextromethorphan at 24, 48 and 72 hr post fertilization (hpf), respectively, during the embryonic/larval development. Compared with the 48 and 72 hpf exposure sets, the embryos/larvae in the 24 hpf exposure set showed much higher mortality rates which increased in a dose-dependent manner. Bradycardia and reduced blood flow were observed for the embryos/larvae treated with increasing concentrations of dextromethorphan. Morphological effects of dextromethorphan exposure, including yolk sac and cardiac edema, craniofacial malformation, lordosis, non-inflated swim bladder and missing gill, were also more frequent and severe among zebrafish embryos/larvae exposed to dextromethorphan at 24 hpf. After treatment with a high-dose of dextromethorphan (40 mg/kg/day) for 2 weeks, rats showed increased depression-like behavior when compared to the control animals. Neurogenesis in the hippocampus was suppressed by dextromethorphan treatment, which was indicated by decreases in number of proliferative cells and immature neurons. Dextromethorphan was not genotoxic in mice. |
| Source: DrugBank or Hazardous Substances Data Bank (HSDB) |