title: Dimethyl trisulfide: A novel cyanide countermeasure.
abstract: In the present studies, the in vitro and in vivo efficacies of a novel cyanide countermeasure, dimethyl trisulfide (DMTS), were evaluated. DMTS is a sulfur-based molecule found in garlic, onion, broccoli, and similar plants. DMTS was studied for effectiveness as a sulfur donor-type cyanide countermeasure. The sulfur donor reactivity of DMTS was determined by measuring the rate of the formation of the cyanide metabolite thiocyanate. In experiments carried out in vitro in the presence of the sulfurtransferase rhodanese (Rh) and at the experimental pH of 7.4, DMTS was observed to convert cyanide to thiocyanate with greater than 40 times higher efficacy than does thiosulfate, the sulfur donor component of the US Food and Drug Administration-approved cyanide countermeasure Nithiodote®In the absence of Rh, DMTS was observed to be almost 80 times more efficient than sodium thiosulfate in vitro The fact that DMTS converts cyanide to thiocyanate more efficiently than does thiosulfate both with and without Rh makes it a promising sulfur donor-type cyanide antidote (scavenger) with reduced enzyme dependence in vitro The therapeutic cyanide antidotal efficacies for DMTS versus sodium thiosulfate were measured following intramuscular administration in a mouse model and expressed as antidotal potency ratios (APR = LD50of cyanide with antidote/LD50of cyanide without antidote). A dose of 100 mg/kg sodium thiosulfate given intramuscularly showed only slight therapeutic protection (APR = 1.1), whereas the antidotal protection from DMTS given intramuscularly at the same dose was substantial (APR = 3.3). Based on these data, DMTS will be studied further as a promising next-generation countermeasure for cyanide intoxication.
authors.affiliation: Analytical Toxicology Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, USA gary.a.rockwood.civ@mail.mil.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Rockwood
authors.affiliation: Department of Chemistry, Sam Houston State University, Huntsville, TX, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Thompson
authors.affiliation: Department of Chemistry, Sam Houston State University, Huntsville, TX, USA.
authors.forename: Ilona
authors.initials: I
authors.lastname: Petrikovics
mesh_terms: D000818:Animals; D000931:Antidotes / Q000737:chemistry / Q000494:pharmacology*; D001937:Brassica / Q000737:chemistry; D003486:Cyanides / Q000737:chemistry / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005737:Garlic / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007273:Injections, Intramuscular; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D019697:Onions / Q000737:chemistry; D013440:Sulfides / Q000494:pharmacology*; D013861:Thiocyanates / Q000378:metabolism; D013884:Thiosulfate Sulfurtransferase / Q000378:metabolism; D013885:Thiosulfates / Q000494:pharmacology
chemical_list: D000931:Antidotes; D003486:Cyanides; D013440:Sulfides; D013861:Thiocyanates; D013885:Thiosulfates; C054170:dimethyl trisulfide; D013884:Thiosulfate Sulfurtransferase; C017717:sodium thiosulfate; C031760:thiocyanate
keywords: CAS#: 3658-80-8); Dimethyl trisulfide (DMTS; cyanide antagonism; in vitro sulfur donor reactivity; therapeutic antidotal efficacy