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
Abstract 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: First, virus dilution for antiviral effects in mice was determined. Then, animals were treated as follows: control (NaCl 250 µL/anim...
Published in: | Journal of Venomous Animals and Toxins including Tropical Diseases |
---|---|
Main Authors: | , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
SciELO
|
Subjects: | |
Online Access: | https://doi.org/10.1590/1678-9199-jvatitd-2019-0050 https://doaj.org/article/9833d13275474bedae53ee7d5ae46c8c |
id |
ftdoajarticles:oai:doaj.org/article:9833d13275474bedae53ee7d5ae46c8c |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:9833d13275474bedae53ee7d5ae46c8c 2023-05-15T15:09:47+02:00 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 Hugo Vigerelli Juliana M. Sciani Patricia M. C. Pereira Aline A. Lavezo Andrea C. R. Silva Rita C. O. Collaço Thalita Rocha Thais C. Bueno Daniel C. Pimenta https://doi.org/10.1590/1678-9199-jvatitd-2019-0050 https://doaj.org/article/9833d13275474bedae53ee7d5ae46c8c EN eng SciELO http://www.scielo.br/pdf/jvatitd/v26/1678-9199-jvatitd-26-e20190050.pdf http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992020000100303&tlng=en https://doaj.org/toc/1678-9199 1678-9199 doi:10.1590/1678-9199-jvatitd-2019-0050 https://doaj.org/article/9833d13275474bedae53ee7d5ae46c8c Journal of Venomous Animals and Toxins including Tropical Diseases Rabies Rabies therapy Bufotenine Arctic medicine. Tropical medicine RC955-962 Toxicology. Poisons RA1190-1270 Zoology QL1-991 article ftdoajarticles https://doi.org/10.1590/1678-9199-jvatitd-2019-0050 2022-12-31T13:42:36Z Abstract 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: 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 (10-6,82CVS dilution); and test (10-6,82 CVS dilution and bufotenine, in the above-mentioned doses). Animals were observed daily for 21 days or until the 3rd stage of rabies infection. Twitch-tension and liposome studies were applied to understand the possible interaction of bufotenine with receptors, particularly acetylcholine. 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: 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Journal of Venomous Animals and Toxins including Tropical Diseases 26 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Rabies Rabies therapy Bufotenine Arctic medicine. Tropical medicine RC955-962 Toxicology. Poisons RA1190-1270 Zoology QL1-991 |
spellingShingle |
Rabies Rabies therapy Bufotenine Arctic medicine. Tropical medicine RC955-962 Toxicology. Poisons RA1190-1270 Zoology QL1-991 Hugo Vigerelli Juliana M. Sciani Patricia M. C. Pereira Aline A. Lavezo Andrea C. R. Silva Rita C. O. Collaço Thalita Rocha Thais C. Bueno Daniel C. Pimenta 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 |
topic_facet |
Rabies Rabies therapy Bufotenine Arctic medicine. Tropical medicine RC955-962 Toxicology. Poisons RA1190-1270 Zoology QL1-991 |
description |
Abstract 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: 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 (10-6,82CVS dilution); and test (10-6,82 CVS dilution and bufotenine, in the above-mentioned doses). Animals were observed daily for 21 days or until the 3rd stage of rabies infection. Twitch-tension and liposome studies were applied to understand the possible interaction of bufotenine with receptors, particularly acetylcholine. 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: 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. |
format |
Article in Journal/Newspaper |
author |
Hugo Vigerelli Juliana M. Sciani Patricia M. C. Pereira Aline A. Lavezo Andrea C. R. Silva Rita C. O. Collaço Thalita Rocha Thais C. Bueno Daniel C. Pimenta |
author_facet |
Hugo Vigerelli Juliana M. Sciani Patricia M. C. Pereira Aline A. Lavezo Andrea C. R. Silva Rita C. O. Collaço Thalita Rocha Thais C. Bueno Daniel C. Pimenta |
author_sort |
Hugo Vigerelli |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
SciELO |
url |
https://doi.org/10.1590/1678-9199-jvatitd-2019-0050 https://doaj.org/article/9833d13275474bedae53ee7d5ae46c8c |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Journal of Venomous Animals and Toxins including Tropical Diseases |
op_relation |
http://www.scielo.br/pdf/jvatitd/v26/1678-9199-jvatitd-26-e20190050.pdf http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992020000100303&tlng=en https://doaj.org/toc/1678-9199 1678-9199 doi:10.1590/1678-9199-jvatitd-2019-0050 https://doaj.org/article/9833d13275474bedae53ee7d5ae46c8c |
op_doi |
https://doi.org/10.1590/1678-9199-jvatitd-2019-0050 |
container_title |
Journal of Venomous Animals and Toxins including Tropical Diseases |
container_volume |
26 |
_version_ |
1766340903125909504 |