Disulfiram

Mechanism: Disulfiram irreversibly inhibits ALDH, particularly ALDH1A1, by competing with NAD at the cysteine residue. This prevents the conversion of acetaldehyde to acetic acid, leading to its accumulation and causing the disulfiram-alcohol reaction, characterized by symptoms such as diaphoresis, palpitations, facial flushing, nausea, vertigo, hypotension, and tachycardia.
Time Course: The disulfiram-alcohol reaction typically begins about 10 minutes after alcohol ingestion and can last for 1 hour or more, as noted in clinical observations (source).

Mechanism: Disulfiram inhibits DBH, the enzyme converting dopamine to norepinephrine, potentially increasing dopamine levels and decreasing norepinephrine, which may underlie its experimental use in cocaine dependence by correcting underlying dopamine deficits.
Time Course: Specific duration data for DBH inhibition is less documented, but given Disulfiram's daily administration, it seems likely that its effects are maintained with regular dosing. Studies on cocaine-related behaviors suggest effects are observed over days with chronic administration, but exact onset and duration remain unclear (source).

Disulfiram also inhibits aldehyde dehydrogenase family 3 member A2 (ALDH3A2) and competitively binds the peripheral benzodiazepine receptor, though these actions are less studied and their clinical significance, including time courses, is not well-established (source).

Half-Life: Disulfiram has a half-life of approximately 7 hours, while its active metabolite, diethyldithiocarbamate (DDTC), has a half-life of about 15 hours. There is significant inter-subject variability, which may stem from differences in metabolism, lipid content, enterohepatic circulation, or protein-binding capacity (source).
Bioavailability: Oral absorption is reported at 80-90%, indicating high bioavailability via the oral route, which is the standard administration method. This high absorption rate is supported by clinical pharmacokinetics data, though exact bioavailability figures may vary due to metabolic conversion to active metabolites (source).

Forms and Administration: Available as 250 mg and 500 mg oral tablets, which can be crushed and mixed with water, coffee, milk, or fruit juice for administration (source).
Safe Range: The recommended safe daily dose is up to 500 mg, with no additional benefit observed above this level (source).
Minimum Effective Dose: Typically ranges from 125 mg to 250 mg daily, with some sources indicating effectiveness at 125 mg, particularly for maintenance therapy (source).
Maximum Dose Without High Risks: 500 mg per day is the maximum recommended dose to avoid significant risks, as higher doses do not enhance efficacy and increase toxicity risk (source).
Toxic Threshold and LD50: Doses above 500 mg per day can lead to toxicity, with clinical manifestations rare below 3 g in a single dose for adults. Lethal doses are estimated at 10-30 g in a single ingestion for humans, based on case reports and clinical observations (source).