Original mechanisms of antipsychotic action by the indole alkaloid alstonine (Picralima nitida)

Autores
Linck, Viviane M.; Ganzella, Marcelo; Herrmann, Ana P.; Okunji, Christopher O.; Souza, Diogo O.; Antonelli, Marta Cristina; Elisabetsky, Elaine
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Alstonine is the major component of plant based remedies that traditional psychiatrists use in Nigeria. Alstonine is an indole alkaloid that has an antipsychotic experimental profile comparable with that of clozapine and is compatible with the alleged effects in mental patients. Representing a desirable innovation in the pharmacodynamics of antipsychotic medications, the evidence indicates that alstonine does not bind to D2 dopamine receptors (D2R) and differentially regulates dopamine in the cortical and limbic areas. The purpose of this study was to further investigate the effects of alstonine on D2R binding in specific brain regions using quantitative autoradiography (QAR) and its effects on dopamine (DA) uptake in mouse striatal synaptosomes. The effects of alstonine on D2R binding were determined in the nucleus accumbens and caudate-putamen using QAR in mice treated with alstonine doses that have antipsychotic effects. The effects of alstonine [3H]DA uptake were assessed in synaptosomes prepared from striatal tissue obtained from mice treated acutely or for 7 days with alstonine. Alstonine did not change the D2R binding densities in the studied regions. DA uptake was increased after acute (but not after 7 days) treatment with alstonine. Consistent with the alstonine behavioral profile, these results indicate that alstonine indirectly modulates DA receptors, specifically by modulating DA uptake. This unique mechanism for DA transmission modulation contributes to the antipsychotic-like effects of alstonine and is compatible with its behavioral profile in mice and alleged effects in patients. These results may represent an innovation in the antipsychotic development field.
Fil: Linck, Viviane M.. Universidade Federal do Rio Grande do Sul; Brasil
Fil: Ganzella, Marcelo. Universidade Federal do Rio Grande do Sul; Brasil
Fil: Herrmann, Ana P.. Universidade Federal do Rio Grande do Sul; Brasil
Fil: Okunji, Christopher O.. International Centre for Ethnomedicine and Drug Development; Nigeria
Fil: Souza, Diogo O.. Universidade Federal do Rio Grande do Sul; Brasil
Fil: Antonelli, Marta Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Elisabetsky, Elaine. Universidade Federal do Rio Grande do Sul; Brasil
Materia
ALSTONINE
ANTIPSYCHOTICS
D2 DOPAMINE RECEPTOR
DOPAMINE UPTAKE
INDOLE ALKALOID
PICRALIMA NITIDA
SCHIZOPHRENIA
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/182647
Acceder
id CONICETDig_f9329a121c24c7e3d9fc4b0c2c80eb89
oai_identifier_str oai:ri.conicet.gov.ar:11336/182647
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Original mechanisms of antipsychotic action by the indole alkaloid alstonine (Picralima nitida)Linck, Viviane M.Ganzella, MarceloHerrmann, Ana P.Okunji, Christopher O.Souza, Diogo O.Antonelli, Marta CristinaElisabetsky, ElaineALSTONINEANTIPSYCHOTICSD2 DOPAMINE RECEPTORDOPAMINE UPTAKEINDOLE ALKALOIDPICRALIMA NITIDASCHIZOPHRENIAhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Alstonine is the major component of plant based remedies that traditional psychiatrists use in Nigeria. Alstonine is an indole alkaloid that has an antipsychotic experimental profile comparable with that of clozapine and is compatible with the alleged effects in mental patients. Representing a desirable innovation in the pharmacodynamics of antipsychotic medications, the evidence indicates that alstonine does not bind to D2 dopamine receptors (D2R) and differentially regulates dopamine in the cortical and limbic areas. The purpose of this study was to further investigate the effects of alstonine on D2R binding in specific brain regions using quantitative autoradiography (QAR) and its effects on dopamine (DA) uptake in mouse striatal synaptosomes. The effects of alstonine on D2R binding were determined in the nucleus accumbens and caudate-putamen using QAR in mice treated with alstonine doses that have antipsychotic effects. The effects of alstonine [3H]DA uptake were assessed in synaptosomes prepared from striatal tissue obtained from mice treated acutely or for 7 days with alstonine. Alstonine did not change the D2R binding densities in the studied regions. DA uptake was increased after acute (but not after 7 days) treatment with alstonine. Consistent with the alstonine behavioral profile, these results indicate that alstonine indirectly modulates DA receptors, specifically by modulating DA uptake. This unique mechanism for DA transmission modulation contributes to the antipsychotic-like effects of alstonine and is compatible with its behavioral profile in mice and alleged effects in patients. These results may represent an innovation in the antipsychotic development field.Fil: Linck, Viviane M.. Universidade Federal do Rio Grande do Sul; BrasilFil: Ganzella, Marcelo. Universidade Federal do Rio Grande do Sul; BrasilFil: Herrmann, Ana P.. Universidade Federal do Rio Grande do Sul; BrasilFil: Okunji, Christopher O.. International Centre for Ethnomedicine and Drug Development; NigeriaFil: Souza, Diogo O.. Universidade Federal do Rio Grande do Sul; BrasilFil: Antonelli, Marta Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Elisabetsky, Elaine. Universidade Federal do Rio Grande do Sul; BrasilElsevier Gmbh2015-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/182647Linck, Viviane M.; Ganzella, Marcelo; Herrmann, Ana P.; Okunji, Christopher O.; Souza, Diogo O.; et al.; Original mechanisms of antipsychotic action by the indole alkaloid alstonine (Picralima nitida); Elsevier Gmbh; Phytomedicine; 22; 1; 1-2015; 52-550944-71131618-095XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.phymed.2014.10.010info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0944711314003651info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-12-23T13:12:31Zoai:ri.conicet.gov.ar:11336/182647instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-12-23 13:12:32.245CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Original mechanisms of antipsychotic action by the indole alkaloid alstonine (Picralima nitida)
title Original mechanisms of antipsychotic action by the indole alkaloid alstonine (Picralima nitida)
spellingShingle Original mechanisms of antipsychotic action by the indole alkaloid alstonine (Picralima nitida)
Linck, Viviane M.
ALSTONINE
ANTIPSYCHOTICS
D2 DOPAMINE RECEPTOR
DOPAMINE UPTAKE
INDOLE ALKALOID
PICRALIMA NITIDA
SCHIZOPHRENIA
title_short Original mechanisms of antipsychotic action by the indole alkaloid alstonine (Picralima nitida)
title_full Original mechanisms of antipsychotic action by the indole alkaloid alstonine (Picralima nitida)
title_fullStr Original mechanisms of antipsychotic action by the indole alkaloid alstonine (Picralima nitida)
title_full_unstemmed Original mechanisms of antipsychotic action by the indole alkaloid alstonine (Picralima nitida)
title_sort Original mechanisms of antipsychotic action by the indole alkaloid alstonine (Picralima nitida)
dc.creator.none.fl_str_mv Linck, Viviane M.
Ganzella, Marcelo
Herrmann, Ana P.
Okunji, Christopher O.
Souza, Diogo O.
Antonelli, Marta Cristina
Elisabetsky, Elaine
author Linck, Viviane M.
author_facet Linck, Viviane M.
Ganzella, Marcelo
Herrmann, Ana P.
Okunji, Christopher O.
Souza, Diogo O.
Antonelli, Marta Cristina
Elisabetsky, Elaine
author_role author
author2 Ganzella, Marcelo
Herrmann, Ana P.
Okunji, Christopher O.
Souza, Diogo O.
Antonelli, Marta Cristina
Elisabetsky, Elaine
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv ALSTONINE
ANTIPSYCHOTICS
D2 DOPAMINE RECEPTOR
DOPAMINE UPTAKE
INDOLE ALKALOID
PICRALIMA NITIDA
SCHIZOPHRENIA
topic ALSTONINE
ANTIPSYCHOTICS
D2 DOPAMINE RECEPTOR
DOPAMINE UPTAKE
INDOLE ALKALOID
PICRALIMA NITIDA
SCHIZOPHRENIA
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Alstonine is the major component of plant based remedies that traditional psychiatrists use in Nigeria. Alstonine is an indole alkaloid that has an antipsychotic experimental profile comparable with that of clozapine and is compatible with the alleged effects in mental patients. Representing a desirable innovation in the pharmacodynamics of antipsychotic medications, the evidence indicates that alstonine does not bind to D2 dopamine receptors (D2R) and differentially regulates dopamine in the cortical and limbic areas. The purpose of this study was to further investigate the effects of alstonine on D2R binding in specific brain regions using quantitative autoradiography (QAR) and its effects on dopamine (DA) uptake in mouse striatal synaptosomes. The effects of alstonine on D2R binding were determined in the nucleus accumbens and caudate-putamen using QAR in mice treated with alstonine doses that have antipsychotic effects. The effects of alstonine [3H]DA uptake were assessed in synaptosomes prepared from striatal tissue obtained from mice treated acutely or for 7 days with alstonine. Alstonine did not change the D2R binding densities in the studied regions. DA uptake was increased after acute (but not after 7 days) treatment with alstonine. Consistent with the alstonine behavioral profile, these results indicate that alstonine indirectly modulates DA receptors, specifically by modulating DA uptake. This unique mechanism for DA transmission modulation contributes to the antipsychotic-like effects of alstonine and is compatible with its behavioral profile in mice and alleged effects in patients. These results may represent an innovation in the antipsychotic development field.
Fil: Linck, Viviane M.. Universidade Federal do Rio Grande do Sul; Brasil
Fil: Ganzella, Marcelo. Universidade Federal do Rio Grande do Sul; Brasil
Fil: Herrmann, Ana P.. Universidade Federal do Rio Grande do Sul; Brasil
Fil: Okunji, Christopher O.. International Centre for Ethnomedicine and Drug Development; Nigeria
Fil: Souza, Diogo O.. Universidade Federal do Rio Grande do Sul; Brasil
Fil: Antonelli, Marta Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Elisabetsky, Elaine. Universidade Federal do Rio Grande do Sul; Brasil
description Alstonine is the major component of plant based remedies that traditional psychiatrists use in Nigeria. Alstonine is an indole alkaloid that has an antipsychotic experimental profile comparable with that of clozapine and is compatible with the alleged effects in mental patients. Representing a desirable innovation in the pharmacodynamics of antipsychotic medications, the evidence indicates that alstonine does not bind to D2 dopamine receptors (D2R) and differentially regulates dopamine in the cortical and limbic areas. The purpose of this study was to further investigate the effects of alstonine on D2R binding in specific brain regions using quantitative autoradiography (QAR) and its effects on dopamine (DA) uptake in mouse striatal synaptosomes. The effects of alstonine on D2R binding were determined in the nucleus accumbens and caudate-putamen using QAR in mice treated with alstonine doses that have antipsychotic effects. The effects of alstonine [3H]DA uptake were assessed in synaptosomes prepared from striatal tissue obtained from mice treated acutely or for 7 days with alstonine. Alstonine did not change the D2R binding densities in the studied regions. DA uptake was increased after acute (but not after 7 days) treatment with alstonine. Consistent with the alstonine behavioral profile, these results indicate that alstonine indirectly modulates DA receptors, specifically by modulating DA uptake. This unique mechanism for DA transmission modulation contributes to the antipsychotic-like effects of alstonine and is compatible with its behavioral profile in mice and alleged effects in patients. These results may represent an innovation in the antipsychotic development field.
publishDate 2015
dc.date.none.fl_str_mv 2015-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/182647
Linck, Viviane M.; Ganzella, Marcelo; Herrmann, Ana P.; Okunji, Christopher O.; Souza, Diogo O.; et al.; Original mechanisms of antipsychotic action by the indole alkaloid alstonine (Picralima nitida); Elsevier Gmbh; Phytomedicine; 22; 1; 1-2015; 52-55
0944-7113
1618-095X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/182647
identifier_str_mv Linck, Viviane M.; Ganzella, Marcelo; Herrmann, Ana P.; Okunji, Christopher O.; Souza, Diogo O.; et al.; Original mechanisms of antipsychotic action by the indole alkaloid alstonine (Picralima nitida); Elsevier Gmbh; Phytomedicine; 22; 1; 1-2015; 52-55
0944-7113
1618-095X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.phymed.2014.10.010
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0944711314003651
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Gmbh
publisher.none.fl_str_mv Elsevier Gmbh
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1852334919852752896
score 13.049097

Publicaciones similares