Why might disulfiram cause parkinsonism?

Label:chem

Topic
Case reports have suggested that disulfiram treatment may lead to parkinsonian syndromes, but epidemiological confirmation has been lacking. The study aimed to assess the risk of incident parkinsonism associated with disulfiram prescribing in a large population. Disulfiram is rapidly reduced in the blood to N, N-diethyldithiocarbamate (DDTC), which then decomposes to carbon disulfide and diethylamine. Carbon disulfide is a known neurotoxicant, and parkinsonism has been a notable outcome of occupational carbon disulfide exposure.
Answer
One study observed a two- to three-fold increased risk of parkinsonism associated with disulfiram, increasing to up to four-fold with a greater number of disulfiram prescriptions. The neurotoxicity of disulfiram has been attributed to its metabolite, N, N-diethyldithiocarbamate (DDTC), which has shown neurological effects in humans and animals. Specifically, the parkinsonism-inducing effects of DDTC may be mediated by its breakdown to carbon disulfide. Blood concentrations of carbon disulfide increase substantially after disulfiram ingestion. Carbon disulfide is known to cause parkinsonism and damages dopaminergic neurons in the substantia nigra. Clinicians and drug regulatory agencies should consider parkinsonism when assessing the risks and benefits of disulfiram use.
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