Repurposing calcium channel blockers and cholinesterase inhibitors for antisnake venom therapy: a mechanistic literature review

Abstract

Snakebite envenomation remains a critical global health challenge, particularly in regions with high snakebite incidence and limited access to effective antivenom. The complex mixture of venom toxins including phospholipases, metalloproteinases, serine proteases, and neurotoxins causes severe systemic and local effects such as neurotoxicity, myotoxicity, and coagulopathy. Given the limitations of current antivenom therapy, there is increasing interest in drug repurposing as an adjunctive treatment strategy. This review explores the potential of calcium channel blockers (CCBs) and cholinesterase inhibitors (ChEIs) as repurposed agents for snakebite management. CCBs, commonly used in cardiovascular medicine, may counteract venom-induced neurotoxicity and muscle paralysis by regulating calcium influx, while ChEIs, by inhibiting acetylcholine degradation, could mitigate neuromuscular dysfunction. Using a structured literature search across databases including PubMed and Scopus, we analyzed the pharmacological mechanisms, potential therapeutic roles, and current evidence supporting these drugs in the context of snake envenomation. Although no experimental or clinical studies have yet confirmed their efficacy as antisnake venom agents, elucidating their mechanistic relevance offers promising directions for future therapeutic development and improved patient outcomes.