Isosorbide Dinitrate

Isosorbide dinitrate (ISDN, CAS 87-33-2) is a clinically commonly used vasodilator, indicated for the treatment of cardiovascular diseases such as angina pectoris and congestive heart failure. In addition, it has demonstrated potential in the management of cyanide poisoning. In studies utilizing rabbits as an animal model, intravenous administration of 1 mg/kg potassium cyanide was followed by intravenous injection of ISDN at a dose of 50 μg/kg (human equivalent dose) at 3, 5, and 7 minutes post-poisoning. The treatment groups exhibited a survival rate of 83.3%, whereas all animals in the control group succumbed. Furthermore, ISDN administration improved vital signs, including pulse and blood pressure, as well as metabolic disturbances such as blood lactate and pH levels. Notably, the group receiving ISDN at 3 minutes post-poisoning demonstrated superior recovery (p < 0.05) [1].

The underlying mechanism of ISDN involves the in vivo generation of nitric oxide (NO), which competitively binds to cytochrome c oxidase, thereby reversing the inhibition of aerobic metabolism induced by cyanide. Additionally, ISDN promotes vasodilation to improve circulation and inhibits excessive activation of cerebral NMDA receptors, thereby alleviating neurotoxicity. Owing to its low cost, wide availability, and suitability for emergency scenarios, ISDN represents a promising antidote for cyanide poisoning. However, limitations such as small sample size and short observation periods should be noted. Nevertheless, administration within 7 minutes post-poisoning can significantly improve short-term survival rates, highlighting ISDN’s considerable potential as a cyanide antidote.

References:

[1] Lavon O, Avrahami A, Eisenkraft A. Effectiveness of isosorbide dinitrate in cyanide poisoning as a function of the administration timing. BMC Pharmacol Toxicol. 2017 Mar 14;18(1):13. doi: 10.1186/s40360-017-0122-0. PMID: 28288687; PMCID: PMC5348846.