Dimethyl trisulfide: A novel cyanide countermeasure

Area of Science:

• Biochemistry
• Toxicology
• Pharmacology

Background:

• Cyanide intoxication poses a significant public health risk.
• Current cyanide antidotes, like Nithiodote®, rely on thiosulfate as a sulfur donor.
• There is a need for more effective and less enzyme-dependent cyanide countermeasures.

Purpose of the Study:

• To evaluate the in vitro and in vivo efficacy of dimethyl trisulfide (DMTS) as a novel cyanide countermeasure.
• To compare the sulfur donor reactivity of DMTS with thiosulfate.
• To assess the therapeutic antidotal efficacy of DMTS in a mouse model.

Main Methods:

• In vitro experiments measured the conversion of cyanide to thiocyanate by DMTS and thiosulfate, with and without the enzyme rhodanese (Rh).
• In vivo studies involved intramuscular administration of DMTS and sodium thiosulfate in a mouse model of cyanide intoxication.
• Antidotal efficacy was quantified using antidotal potency ratios (APR).

Main Results:

• DMTS demonstrated significantly higher efficacy than thiosulfate in converting cyanide to thiocyanate in vitro, both with ( >40 times) and without ( ~80 times) Rh.
• In vivo, DMTS provided substantial therapeutic protection (APR = 3.3) compared to sodium thiosulfate (APR = 1.1) at a dose of 100 mg/kg.
• DMTS exhibited reduced enzyme dependence compared to thiosulfate.

Conclusions:

• Dimethyl trisulfide (DMTS) is a highly effective sulfur donor-type cyanide antidote with reduced enzyme dependence.
• DMTS shows superior in vitro and in vivo efficacy compared to sodium thiosulfate.
• DMTS represents a promising candidate for a next-generation cyanide countermeasure.