title: Nitrocobinamide, a new cyanide antidote that can be administered by intramuscular injection.
abstract: Currently available cyanide antidotes must be given by intravenous injection over 5-10 min, making them ill-suited for treating many people in the field, as could occur in a major fire, an industrial accident, or a terrorist attack. These scenarios call for a drug that can be given quickly, e.g., by intramuscular injection. We have shown that aquohydroxocobinamide is a potent cyanide antidote in animal models of cyanide poisoning, but it is unstable in solution and poorly absorbed after intramuscular injection. Here we show that adding sodium nitrite to cobinamide yields a stable derivative (referred to as nitrocobinamide) that rescues cyanide-poisoned mice and rabbits when given by intramuscular injection. We also show that the efficacy of nitrocobinamide is markedly enhanced by coadministering sodium thiosulfate (reducing the total injected volume), and we calculate that ∼1.4 mL each of nitrocobinamide and sodium thiosulfate should rescue a human from a lethal cyanide exposure.
authors: Departments of †Medicine, ‡Pathology, §Chemistry and Biochemistry, and ∥Anesthesiology, University of California-San Diego , La Jolla, California 92093-0652, United States.
authors: Adriano
authors: A
authors: Chan
authors: Jingjing
authors: J
authors: Jiang
authors: Alla
authors: A
authors: Fridman
authors: Ling T
authors: LT
authors: Guo
authors: G Diane
authors: GD
authors: Shelton
authors: Ming-Tao
authors: MT
authors: Liu
authors: Carol
authors: C
authors: Green
authors: Kristofer J
authors: KJ
authors: Haushalter
authors: Hemal H
authors: HH
authors: Patel
authors: Jangwoen
authors: J
authors: Lee
authors: David
authors: D
authors: Yoon
authors: Tanya
authors: T
authors: Burney
authors: David
authors: D
authors: Mukai
authors: Sari B
authors: SB
authors: Mahon
authors: Matthew
authors: M
authors: Brenner
authors: Renate B
authors: RB
authors: Pilz
authors: Gerry R
authors: GR
authors: Boss
mesh_terms: D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D003038:Cobamides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D003486:Cyanides / Q000506:poisoning*; D004305:Dose-Response Relationship, Drug; D007273:Injections, Intramuscular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects; D011817:Rabbits; D012977:Sodium Nitrite / Q000737:chemistry; D013329:Structure-Activity Relationship; D013885:Thiosulfates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000931:Antidotes; D003038:Cobamides; D003486:Cyanides; D013885:Thiosulfates; C000597467:nitrocobinamide; C017142:cobinamide; C017717:sodium thiosulfate; D012977:Sodium Nitrite
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