Comparison of the efficacy of varespladib and coral snake antivenom against the activities of the Amazon coral snake (Micrurus spixii) venom.

The ability of varespladib (VPL), a phospholipase A2 (PLA2) inhibitor, to attenuate several activities of the Amazon coral snake (Micrurus spixii) venom was assessed. The neutralization by VPL was compared to that of coral snake antivenom and, in some cases, neostigmine. The venom showed anticoagulant activity in human plasma (assessed using in vitro thromboelastometry), and was myotoxic (based on the increase in serum creatine kinase activity) and lethal to mice, in addition to causing neuromuscular blockade in chick isolated biventer cervicis preparations. Antivenom fully protected against lethality but only partially neutralized the other activities at the doses tested. VPL attenuated PLA2-dependent effects, including anticoagulant activity and myotoxicity, but did not abrogate lethality. A combination of VPL and antivenom was also effective against anticoagulant activity and myotoxicity. Antivenom and VPL were partially effective for inhibiting the neuromuscular blockade induced by the venom, suggesting that toxins other than PLA2s might be also involved. Antivenom and Varespladib combined have a higher inhibition than each of them alone against anticoagulant, myotoxic and neuromuscular blocking effects. Neostigmine, an anticholinesterase drug, showed only modest protection against lethality and neuromuscular blockade. These findings suggest that VPL could be a potential adjunct to conventional antivenom therapy in treating envenomation by M. spixii.