Sodasulphanecobalamin provides rapid cyanide detoxification and hemodynamic rescue in a rat model of acute cyanide poisoning.

Current cyanide antidotes have limitations including delayed onset, methemoglobinemia, or the need for multiple agents. We developed Sodasulphanecobalamin (SSC), a cobalt‑sulfur complex integrating rapid cyanide chelation with sulfur-donor detoxification. SSC was synthesized from hydroxocobalamin and sulfur-based precursors, characterized by HPLC, HR-MS, NMR, IR, and elemental analysis, with the coordination geometry pending X-ray crystallography. In rats, SSC given 1 or 5 min after intravenous KCN (2.5 mg/kg) restored mean arterial pressure (MAP) within 5 ± 1 and 9 ± 2 min, respectively, with 100% survival in both groups (n = 9). At a higher cyanide dose (3.5 mg/kg, ∼1.7× LD₅₀), SSC given after 5 min maintained 100% survival (n = 6), whereas hydroxocobalamin resulted in 83% survival. SSC (78% yield, >98% purity) restored MAP significantly faster than hydroxocobalamin (11 ± 2 min, p = 0.032) and standard nitrite-thiosulfate therapy (28 ± 3 min, p = 0.0004). At 3.5 mg/kg, SSC achieved 100% survival vs. 83% for hydroxocobalamin and 67% for standard therapy. Blood cyanide declined 85% within 5 min with corresponding thiocyanate rise, and methemoglobin remained below 3% (p > 0.05 vs. controls). Naive rats showed no toxicity over 28 days. Pharmacokinetics revealed a half-life of 4.2 ± 0.6 h. SSC is a fast-acting, well-tolerated cyanide antidote outperforming current therapies. Further studies are needed for dosing optimization and intramuscular administration.