Usefulness of the combination of a single dose of neostigmine-atropine plus antivenom on the experimental treatment of the envenomation caused by Micrurus venoms.
- 1Primera Catedra de Toxicologia, Carrera de Medicina, Facultad de Ciencias Medicas, Universidad de Buenos Aires. Paraguay 2155, CP 1121, CABA, Argentina.
- 2Area Investigacion y Desarrollo - Venenos. Instituto Nacional de Produccion de Biologicos, Administracion Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbran". Av. Velez Sarsfield 563, CP1282, CABA, Argentina.
Abstract
Envenomation by Micrurus snakes is relatively infrequent, but constitutes a persistent public health concern throughout the Americas, due to its potentially severe clinical consequences. The venom of these snakes, like that of other elapids, primarily contains postsynaptic toxins (α-neurotoxins, with a three-finger toxin (3-FTx) structure) and some species also produce presynaptic toxins (β-neurotoxins, with a phospholipase A2 (PLA2) structure). Given this composition, the potential therapeutic value of combining an acetylcholinesterase inhibitor, neostigmine (N) plus atropine (A) with an anti-Micrurus antivenom (AV) was investigated. The efficacy of this combination therapy was evaluated in comparison to AV alone, using experimental envenomation models involving Micrurus venoms with different proportions of 3-FTxs and PLA2s. Groups of mice were challenged with 1.2 minimal mortal doses of M. pyrrhocryptus (Mp), M. altirostris (Ma), M. surinamensis (Ms), M. nigrocinctus (Mn), or M. fulvius (Mf) venom. After 15 minutes, the animals received a single rescue treatment with either N+A, various doses of anti-Micrurus AV alone, or a combination of AV plus N+A. Survival was assessed at 24 hours. For the venom control groups and those treated with N+A alone, time to death was also recorded. The median effective dose of AV alone, or with the addition of N+A, was estimated for Mp and Ma venoms. Treatment with the N+A combination alone did not provide effective protection. However, N+A slightly delayed the time to death in animals envenomed with Ms, Ma, and Mp venoms (p < 0.05). The combination of N+A with AV significantly improved survival compared to AV alone in mice challenged with Ma and Mp venoms (p < 0.05). In contrast, higher AV doses were required to achieve similar effects in animals envenomed with Ms venom, while Mn and Mf venoms required the highest AV doses to show some level of protection. The estimated median effective dose of AV in combination with N+A was more potent, enhancing AV potency by 1.6-fold for Mp and up to 3.4-fold for Ma venom. The survival of mice treated with AV plus N+A was higher in envenomations caused by Ma, Ms, and Mp venoms, which are characterized by prominent α-neurotoxic activity and a lower proportion of PLA2s. The effect was less evident and only apparent at the highest AV doses for Mn and Mf venoms, which contain higher levels of PLA2s and exhibit strong experimental myotoxic capacity. The results show that the combined use of N+A and AV enhances the effectiveness of treatment in Micrurus envenomations, especially those involving predominantly postsynaptic neurotoxins, by reducing the AV dose required for recovery.
Related
- Strengthening public health programmes and the antivenom ecosystem: strategic policy priorities to combat envenomation by animal bites and stings in Latin America and the Caribbean.
- Rutin (quercetin-3-rutinoside) administered orally after experimental Bothrops jararaca envenomation prevents hemostatic, inflammatory and hemorrhagic disturbances
- Suspected Microvascular Occlusion Syndrome Following Scorpion Envenomation: A Pediatric Case Report
- Purinergic Signalling in Snakebite Envenomation: Mechanistic Insights, Therapeutic Targets and Future Perspectives
- Envenomation Leads to Venom Protein Reduction and a Recovery Period in Bumblebee Workers
BibTeX
@article{roodt2026usefulness,
title = {{Usefulness of the combination of a single dose of neostigmine-atropine plus antivenom on the experimental treatment of the envenomation caused by Micrurus venoms.}},
author = {Adolfo Rafael DE Roodt and Daniel Dozoretz and Fernando Andrés Morón Goñi and Marcela Alejandra Desio and Carlos Fabián Damín},
journal = {Medecine tropicale et sante internationale},
year = {2026},
month = jul,
doi = {10.48327/mtsi.v6i3.2026.871},
url = {https://europepmc.org/article/MED/42953169},
note = {CC BY},
}
RIS
TY - JOUR
TI - Usefulness of the combination of a single dose of neostigmine-atropine plus antivenom on the experimental treatment of the envenomation caused by Micrurus venoms.
AU - Adolfo Rafael DE Roodt
AU - Daniel Dozoretz
AU - Fernando Andrés Morón Goñi
AU - Marcela Alejandra Desio
AU - Carlos Fabián Damín
PY - 2026
DA - 2026/07/02
JO - Medecine tropicale et sante internationale
DO - 10.48327/mtsi.v6i3.2026.871
UR - https://europepmc.org/article/MED/42953169
AB - Envenomation by Micrurus snakes is relatively infrequent, but constitutes a persistent public health concern throughout the Americas, due to its potentially severe clinical consequences. The venom of these snakes, like that of other elapids, primarily contains postsynaptic toxins (α-neurotoxins, with a three-finger toxin (3-FTx) structure) and some species also produce presynaptic toxins (β-neurotoxins, with a phospholipase A2 (PLA2) structure). Given this composition, the potential therapeutic value of combining an acetylcholinesterase inhibitor, neostigmine (N) plus atropine (A) with an anti-Micrurus antivenom (AV) was investigated. The efficacy of this combination therapy was evaluated in comparison to AV alone, using experimental envenomation models involving Micrurus venoms with different proportions of 3-FTxs and PLA2s. Groups of mice were challenged with 1.2 minimal mortal doses of M. pyrrhocryptus (Mp), M. altirostris (Ma), M. surinamensis (Ms), M. nigrocinctus (Mn), or M. fulvius (Mf) venom. After 15 minutes, the animals received a single rescue treatment with either N+A, various doses of anti-Micrurus AV alone, or a combination of AV plus N+A. Survival was assessed at 24 hours. For the venom control groups and those treated with N+A alone, time to death was also recorded. The median effective dose of AV alone, or with the addition of N+A, was estimated for Mp and Ma venoms. Treatment with the N+A combination alone did not provide effective protection. However, N+A slightly delayed the time to death in animals envenomed with Ms, Ma, and Mp venoms (p < 0.05). The combination of N+A with AV significantly improved survival compared to AV alone in mice challenged with Ma and Mp venoms (p < 0.05). In contrast, higher AV doses were required to achieve similar effects in animals envenomed with Ms venom, while Mn and Mf venoms required the highest AV doses to show some level of protection. The estimated median effective dose of AV in combination with N+A was more potent, enhancing AV potency by 1.6-fold for Mp and up to 3.4-fold for Ma venom. The survival of mice treated with AV plus N+A was higher in envenomations caused by Ma, Ms, and Mp venoms, which are characterized by prominent α-neurotoxic activity and a lower proportion of PLA2s. The effect was less evident and only apparent at the highest AV doses for Mn and Mf venoms, which contain higher levels of PLA2s and exhibit strong experimental myotoxic capacity. The results show that the combined use of N+A and AV enhances the effectiveness of treatment in Micrurus envenomations, especially those involving predominantly postsynaptic neurotoxins, by reducing the AV dose required for recovery.
SN - 2778-2034
ER -