title: Original mechanisms of antipsychotic action by the indole alkaloid alstonine (Picralima nitida).
abstract: 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.
authors: Laboratório de Etnofarmacologia, Departamento de Farmacologia, Universidade Federal do Rio Grande do Sul, Avenida Sarmento Leite, 500, 90050-170, Porto Alegre, RS, Brazil ; Programa de Pós-graduação em Ciências Biológicas: Bioquímica Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Avenida Sarmento Leite, 500, 90050-170, Porto Alegre, RS, Brazil . Electronic address: vivilinck@gmail.com.
authors: Viviane M
authors: VM
authors: Linck
authors: Programa de Pós-graduação em Ciências Biológicas: Bioquímica Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Avenida Sarmento Leite, 500, 90050-170, Porto Alegre, RS, Brazil.
authors: Marcelo
authors: M
authors: Ganzella
authors: Laboratório de Etnofarmacologia, Departamento de Farmacologia, Universidade Federal do Rio Grande do Sul, Avenida Sarmento Leite, 500, 90050-170, Porto Alegre, RS, Brazil ; Programa de Pós-graduação em Ciências Biológicas: Bioquímica Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Avenida Sarmento Leite, 500, 90050-170, Porto Alegre, RS, Brazil.
authors: Ana P
authors: AP
authors: Herrmann
authors: International Centre for Ethnomedicine and Drug Development (InterCEDD), 110 Aku Road, Nsukka, EnuguState, Nigeria.
authors: Christopher O
authors: CO
authors: Okunji
authors: Programa de Pós-graduação em Ciências Biológicas: Bioquímica Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Avenida Sarmento Leite, 500, 90050-170, Porto Alegre, RS, Brazil.
authors: Diogo O
authors: DO
authors: Souza
authors: Laboratório de Programación Perinatal del Neurodesarrollo, Instituto de Biologia Celular y Neurociencias "Dr E.D.P. De Robertis", Facultad de Medicina, Universidad de Buenos Aires, Uriburu 951 6º piso, C1114AAC, Buenos Aires, Argentina.
authors: Marta C
authors: MC
authors: Antonelli
authors: Laboratório de Etnofarmacologia, Departamento de Farmacologia, Universidade Federal do Rio Grande do Sul, Avenida Sarmento Leite, 500, 90050-170, Porto Alegre, RS, Brazil ; Programa de Pós-graduação em Ciências Biológicas: Bioquímica Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Avenida Sarmento Leite, 500, 90050-170, Porto Alegre, RS, Brazil.
authors: Elaine
authors: E
authors: Elisabetsky
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D029062:Apocynaceae / Q000737:chemistry*; D001345:Autoradiography; D004298:Dopamine / Q000378:metabolism; D005638:Fruit / Q000737:chemistry; D008297:Male; D051379:Mice; D009714:Nucleus Accumbens / Q000187:drug effects; D011699:Putamen / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D046948:Secologanin Tryptamine Alkaloids / Q000493:pharmacokinetics / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D046948:Secologanin Tryptamine Alkaloids; C009244:serpentine (alkaloid); D004298:Dopamine
keywords: Alstonine; Antipsychotics; D(2) dopamine receptor; Dopamine uptake; Indole alkaloid; Picralima nitida; Schizophrenia