Bufotenine, a tryptophan-derived alkaloid, suppresses the symptoms and increases the survival rate of rabies-infected mice: the development of a pharmacological approach for rabies treatment.
Bufotenine
Rabies
Rabies therapy
Journal
The journal of venomous animals and toxins including tropical diseases
ISSN: 1678-9199
Titre abrégé: J Venom Anim Toxins Incl Trop Dis
Pays: Brazil
ID NLM: 101201501
Informations de publication
Date de publication:
2020
2020
Historique:
received:
19
08
2019
accepted:
19
12
2019
entrez:
20
2
2020
pubmed:
20
2
2020
medline:
20
2
2020
Statut:
epublish
Résumé
Between 40,000-70,000 people die yearly of rabies, an incurable disease. Besides post-bite vaccination, no treatment is available for it. First, virus dilution for antiviral effects in mice was determined. Then, animals were treated as follows: control (NaCl 250 µL/animal/day); bufotenine (0.63, 1.05 and 2.1 mg in 250 µL of NaCl/animal/day); rabies (10 Bufotenine was able to increase the survival rate of intracerebrally virus-infected mice from 15 to 40%. Bufotenine did not seem to interfere with the acetylcholine response in the skeletal muscle, indicating that its mechanism of action is not blocking the virus entrance due to nAChR antagonism. By analyzing liposomes, we could observe that bufotenine did not passively penetrates cell membranes, indicating the necessity of complementary structures to cell penetration. Bufotenine is a promising candidate for drug development. After further chemical modification, it might be possible to dissociate minor side effects, increase efficiency, efficacy and pharmacokinetics, yielding a true anti-rabies drug.
Sections du résumé
BACKGROUND
BACKGROUND
Between 40,000-70,000 people die yearly of rabies, an incurable disease. Besides post-bite vaccination, no treatment is available for it.
METHODS
METHODS
First, virus dilution for antiviral effects in mice was determined. Then, animals were treated as follows: control (NaCl 250 µL/animal/day); bufotenine (0.63, 1.05 and 2.1 mg in 250 µL of NaCl/animal/day); rabies (10
RESULTS
RESULTS
Bufotenine was able to increase the survival rate of intracerebrally virus-infected mice from 15 to 40%. Bufotenine did not seem to interfere with the acetylcholine response in the skeletal muscle, indicating that its mechanism of action is not blocking the virus entrance due to nAChR antagonism. By analyzing liposomes, we could observe that bufotenine did not passively penetrates cell membranes, indicating the necessity of complementary structures to cell penetration.
CONCLUSIONS
CONCLUSIONS
Bufotenine is a promising candidate for drug development. After further chemical modification, it might be possible to dissociate minor side effects, increase efficiency, efficacy and pharmacokinetics, yielding a true anti-rabies drug.
Identifiants
pubmed: 32071597
doi: 10.1590/1678-9199-JVATITD-2019-0050
pmc: PMC6996410
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e20190050Déclaration de conflit d'intérêts
Competing interests: The authors declare that they have no competing interests.
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