Agonists of melatonin receptors strongly promote the functional recovery from the neuroparalysis induced by neurotoxic snakes

Giorgia D’Este, Federico Fabris, Marco Stazi, Chiara Baggio, Morena Simonato, Aram Megighian, Michela Rigoni, Samuele Negro and Cesare Montecucco

PLOS Neglected Tropical Diseases, 2024, vol. 18, issue 1, 1-17

Abstract: Snake envenoming is a major, but neglected, tropical disease. Among venomous snakes, those inducing neurotoxicity such as kraits (Bungarus genus) cause a potentially lethal peripheral neuroparalysis with respiratory deficit in a large number of people each year. In order to prevent the development of a deadly respiratory paralysis, hospitalization with pulmonary ventilation and use of antivenoms are the primary therapies currently employed. However, hospitals are frequently out of reach for envenomated patients and there is a general consensus that additional, non-expensive treatments, deliverable even long after the snake bite, are needed. Traumatic or toxic degenerations of peripheral motor neurons cause a neuroparalysis that activates a pro-regenerative intercellular signaling program taking place at the neuromuscular junction (NMJ). We recently reported that the intercellular signaling axis melatonin-melatonin receptor 1 (MT1) plays a major role in the recovery of function of the NMJs after degeneration of motor axon terminals caused by massive Ca2+ influx. Here we show that the small chemical MT1 agonists: Ramelteon and Agomelatine, already licensed for the treatment of insomnia and depression, respectively, are strong promoters of the neuroregeneration after paralysis induced by krait venoms in mice, which is also Ca2+ mediated. The venom from a Bungarus species representative of the large class of neurotoxic snakes (including taipans, coral snakes, some Alpine vipers in addition to other kraits) was chosen. The functional recovery of the NMJ was demonstrated using electrophysiological, imaging and lung ventilation detection methods. According to the present results, we propose that Ramelteon and Agomelatine should be tested in human patients bitten by neurotoxic snakes acting presynaptically to promote their recovery of health. Noticeably, these drugs are commercially available, safe, non-expensive, have a long bench life and can be administered long after a snakebite even in places far away from health facilities.Author summary: Snakebite envenomings cause important tropical human diseases that often include a lethal muscle paralysis. Current treatments consist in hospitalization and antivenoms, which are not always quickly accessible to victims. In fact, these snakebites take place mainly in rural and low-income countries.

Date: 2024
References: Add references at CitEc
Citations:

Downloads: (external link)
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0011825 (text/html)
https://journals.plos.org/plosntds/article/file?id ... 11825&type=printable (application/pdf)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:plo:pntd00:0011825

DOI: 10.1371/journal.pntd.0011825

Access Statistics for this article

More articles in PLOS Neglected Tropical Diseases from Public Library of Science
Bibliographic data for series maintained by plosntds ().