Neostigmine in the Treatment of Elapidae Bites

Determination of Residual Solvents in Neostigmine Methylsulfate by Headspace Gas Chromatography.

“…Neostigmine methylsulfate is a acetylcholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine and is currently recommended by the WHO for the treatment of neurotoxic snakebite [1][2][3][4].…”

Small Molecule Therapeutics for the Initial and Adjunctive Treatment of Snakebite

“…Examples of successfully repurposed drugs include Thalomid (Thalidomide) for side effects of leprosy and Viagra (Sildenafil) for pulmonary hypertension [20,69]. In 1972, Banerjee et al presented an early example of repurposing an SMT for snakebite when neostigmine was used to treat the paralytic effects of an elapid bite [52]. Multiple groups have since investigated the use of this class of acetylcholinesterase inhibitors in the clinical setting with variable results [52,61,65,66].…”

“…In 1972, Banerjee et al presented an early example of repurposing an SMT for snakebite when neostigmine was used to treat the paralytic effects of an elapid bite [52]. Multiple groups have since investigated the use of this class of acetylcholinesterase inhibitors in the clinical setting with variable results [52,61,65,66]. Development of a hypothetical SMT using a repurposing pathway are shown in Figure 4.…”

“…sPLA2s are also some of the most pharmacologically active, multi-effect (neuro-myo-cyto-hemotoxic) venom components ( While sPLA2 inhibition might prove sufficient as a "bridge-to-survival" for many types of venoms when administered in a pre-referral setting and, at times, be sufficient for treatment, future SMTs might be mixtures of other SMT (Figure 3a). Some targets could also be inhibited indirectly by SMTs, such as three-finger toxins, whose effects might sometimes be mitigated by acetylcholinesterase inhibitors, though the use of these inhibitors remains controversial despite decades of use for this purpose [52,61,[64][65][66]. In addition, SMTs might be used to slow the spread of venom by paralyzing lymphatic smooth muscles (e.g., with lignocaine) [67].…”

“…Proteomic analysis has revealed a wide array of active toxic ingredients from at least 26 protein families, but the most common medically relevant components are found within four families in varying proportions [49][50][51]. These proteins are the phospholipase A2 (PLA2s), snake venom metallo-and serine-proteases (svMPs and SPs, respectively), and the non-enzymatic three-finger toxins (3-FTX) [41,[50][51][52]. Not all snake venoms, however, have unique toxins that are in this group of four, including mambas with dendrotoxins and some rattlesnakes with low molecular mass cationic myotoxins [53][54][55].…”