Early Treatment with Intranasal Neostigmine Reduces Mortality in a Mouse Model of Naja naja (Indian Cobra) Envenomation
Objective. Most snakebite deaths occur prior to hospital arrival; yet inexpensive, effective, and easy to administer out-of-hospital treatments do not exist. Acetylcholinesterase inhibitors can be therapeutic in neurotoxic envenomations when administered intravenously, but nasally delivered drugs co...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Journal of Tropical Medicine |
| Online Access: | http://dx.doi.org/10.1155/2014/131835 |
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| author | Matthew R. Lewin Stephen P. Samuel David S. Wexler Philip Bickler Sakthivel Vaiyapuri Brett D. Mensh |
| author_facet | Matthew R. Lewin Stephen P. Samuel David S. Wexler Philip Bickler Sakthivel Vaiyapuri Brett D. Mensh |
| author_sort | Matthew R. Lewin |
| collection | DOAJ |
| description | Objective. Most snakebite deaths occur prior to hospital arrival; yet inexpensive, effective, and easy to administer out-of-hospital treatments do not exist. Acetylcholinesterase inhibitors can be therapeutic in neurotoxic envenomations when administered intravenously, but nasally delivered drugs could facilitate prehospital therapy for these patients. We tested the feasibility of this idea in experimentally envenomed mice. Methods. Mice received intraperitoneal injections of Naja naja venom 2.5 to 10 times the estimated LD50 and then received 5 μL neostigmine (0.5 mg/mL) or 5 μL normal saline by nasal administration. Animals were observed up to 12 hours and survivors were euthanized. Results. 100% of control mice died. Untreated mice injected with 2.5× LD50 Naja naja died at average 193 minutes after injection, while 10 of 15 (67%) of treated mice survived and were behaviorally normal by 6 hours (P<0.02). In the 5× LD50 group, survival was prolonged from 45 minutes to 196 minutes (P=0.01) and for 10× LD50 mice, survival increased from 30 to 175 minutes (P<0.02). Conclusion. This pilot suggests that intranasal drugs can improve survival and is the first direct demonstration that such an approach is plausible, suggesting means by which treatment could be initiated before reaching the hospital. Further investigation of this approach to neurotoxic and other types of envenomation is warranted. |
| format | Article |
| id | doaj-art-9c5f5d0002284f22bcda2bdaa64f391b |
| institution | Kabale University |
| issn | 1687-9686 1687-9694 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Tropical Medicine |
| spelling | doaj-art-9c5f5d0002284f22bcda2bdaa64f391b2025-02-03T05:54:18ZengWileyJournal of Tropical Medicine1687-96861687-96942014-01-01201410.1155/2014/131835131835Early Treatment with Intranasal Neostigmine Reduces Mortality in a Mouse Model of Naja naja (Indian Cobra) EnvenomationMatthew R. Lewin0Stephen P. Samuel1David S. Wexler2Philip Bickler3Sakthivel Vaiyapuri4Brett D. Mensh5Center for Exploration and Travel Health, California Academy of Sciences, 55 Music Concourse Drive, San Francisco, CA 94118, USADepartment of Clinical Medicine, Trinity College Dublin, Dublin 2, IrelandDepartment of Chemistry and Biochemistry, University of California, Berkeley, Berkeley, CA 94920, USADepartment of Anesthesia and Perioperative Care, 505 Parnassus Avenue, University of California, San Francisco, CA 94122, USAInstitute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Reading, UKJanelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USAObjective. Most snakebite deaths occur prior to hospital arrival; yet inexpensive, effective, and easy to administer out-of-hospital treatments do not exist. Acetylcholinesterase inhibitors can be therapeutic in neurotoxic envenomations when administered intravenously, but nasally delivered drugs could facilitate prehospital therapy for these patients. We tested the feasibility of this idea in experimentally envenomed mice. Methods. Mice received intraperitoneal injections of Naja naja venom 2.5 to 10 times the estimated LD50 and then received 5 μL neostigmine (0.5 mg/mL) or 5 μL normal saline by nasal administration. Animals were observed up to 12 hours and survivors were euthanized. Results. 100% of control mice died. Untreated mice injected with 2.5× LD50 Naja naja died at average 193 minutes after injection, while 10 of 15 (67%) of treated mice survived and were behaviorally normal by 6 hours (P<0.02). In the 5× LD50 group, survival was prolonged from 45 minutes to 196 minutes (P=0.01) and for 10× LD50 mice, survival increased from 30 to 175 minutes (P<0.02). Conclusion. This pilot suggests that intranasal drugs can improve survival and is the first direct demonstration that such an approach is plausible, suggesting means by which treatment could be initiated before reaching the hospital. Further investigation of this approach to neurotoxic and other types of envenomation is warranted.http://dx.doi.org/10.1155/2014/131835 |
| spellingShingle | Matthew R. Lewin Stephen P. Samuel David S. Wexler Philip Bickler Sakthivel Vaiyapuri Brett D. Mensh Early Treatment with Intranasal Neostigmine Reduces Mortality in a Mouse Model of Naja naja (Indian Cobra) Envenomation Journal of Tropical Medicine |
| title | Early Treatment with Intranasal Neostigmine Reduces Mortality in a Mouse Model of Naja naja (Indian Cobra) Envenomation |
| title_full | Early Treatment with Intranasal Neostigmine Reduces Mortality in a Mouse Model of Naja naja (Indian Cobra) Envenomation |
| title_fullStr | Early Treatment with Intranasal Neostigmine Reduces Mortality in a Mouse Model of Naja naja (Indian Cobra) Envenomation |
| title_full_unstemmed | Early Treatment with Intranasal Neostigmine Reduces Mortality in a Mouse Model of Naja naja (Indian Cobra) Envenomation |
| title_short | Early Treatment with Intranasal Neostigmine Reduces Mortality in a Mouse Model of Naja naja (Indian Cobra) Envenomation |
| title_sort | early treatment with intranasal neostigmine reduces mortality in a mouse model of naja naja indian cobra envenomation |
| url | http://dx.doi.org/10.1155/2014/131835 |
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