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Alstonine as an antipsychotic: effects on brain amines and metabolic changes.

Linck VM, Herrmann AP, Piato AL, Detanico BC, Figueiró M, Flório J, Iwu MM, Okunji CO, Leal MB, Elisabetsky E - Evid Based Complement Alternat Med (2011)

Bottom Line: Moreover, even with newer drugs, a sizable proportion of patients do not show significant improvement.In relation to possible side effects, preliminary data suggest that alstonine does not affect prolactin levels, does not induce gains in body weight, but prevents the expected fasting-induced decrease in glucose levels.Overall, this study reinforces the proposal that alstonine is a potential innovative antipsychotic, and that a comprehensive understanding of its neurochemical basis may open new avenues to developing newer antipsychotic medications.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Etnofamacologia, ICBS, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite 500/202, 90050-170 Porto Alegre, RS, Brazil.

ABSTRACT
Managing schizophrenia has never been a trivial matter. Furthermore, while classical antipsychotics induce extrapyramidal side effects and hyperprolactinaemia, atypical antipsychotics lead to diabetes, hyperlipidaemia, and weight gain. Moreover, even with newer drugs, a sizable proportion of patients do not show significant improvement. Alstonine is an indole alkaloid identified as the major component of a plant-based remedy used in Nigeria to treat the mentally ill. Alstonine presents a clear antipsychotic profile in rodents, apparently with differential effects in distinct dopaminergic pathways. The aim of this study was to complement the antipsychotic profile of alstonine, verifying its effects on brain amines in mouse frontal cortex and striatum. Additionally, we examined if alstonine induces some hormonal and metabolic changes common to antipsychotics. HPLC data reveal that alstonine increases serotonergic transmission and increases intraneuronal dopamine catabolism. In relation to possible side effects, preliminary data suggest that alstonine does not affect prolactin levels, does not induce gains in body weight, but prevents the expected fasting-induced decrease in glucose levels. Overall, this study reinforces the proposal that alstonine is a potential innovative antipsychotic, and that a comprehensive understanding of its neurochemical basis may open new avenues to developing newer antipsychotic medications.

No MeSH data available.


Related in: MedlinePlus

Alstonine.
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fig1: Alstonine.

Mentions: The indole alkaloid alstonine (Figure 1) was identified as the major component of a plant-based treatment given to mentally ill patients in Nigeria [13]. Alstonine shows a clear antipsychotic profile in rodents, closer to atypical than to classical agents [14]. Apparently, alstonine induces dissimilar effects in dopaminergic pathways: while apomorphine-induced stereotypy and amphetamine-induced lethality were significantly reduced by alstonine, suggesting a decrease in mesolimbic DA, alstonine reversed haloperidol-induced catalepsy, indicating that nigrostriatal dopamine transmission is not lessened [14]. Relevant for the treatment of negative symptoms, alstonine also presents anxiolytic properties, involving 5HT2A,C receptors, and reverses interaction deficits induced by MK801 [15, 16].


Alstonine as an antipsychotic: effects on brain amines and metabolic changes.

Linck VM, Herrmann AP, Piato AL, Detanico BC, Figueiró M, Flório J, Iwu MM, Okunji CO, Leal MB, Elisabetsky E - Evid Based Complement Alternat Med (2011)

Alstonine.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3140158&req=5

fig1: Alstonine.
Mentions: The indole alkaloid alstonine (Figure 1) was identified as the major component of a plant-based treatment given to mentally ill patients in Nigeria [13]. Alstonine shows a clear antipsychotic profile in rodents, closer to atypical than to classical agents [14]. Apparently, alstonine induces dissimilar effects in dopaminergic pathways: while apomorphine-induced stereotypy and amphetamine-induced lethality were significantly reduced by alstonine, suggesting a decrease in mesolimbic DA, alstonine reversed haloperidol-induced catalepsy, indicating that nigrostriatal dopamine transmission is not lessened [14]. Relevant for the treatment of negative symptoms, alstonine also presents anxiolytic properties, involving 5HT2A,C receptors, and reverses interaction deficits induced by MK801 [15, 16].

Bottom Line: Moreover, even with newer drugs, a sizable proportion of patients do not show significant improvement.In relation to possible side effects, preliminary data suggest that alstonine does not affect prolactin levels, does not induce gains in body weight, but prevents the expected fasting-induced decrease in glucose levels.Overall, this study reinforces the proposal that alstonine is a potential innovative antipsychotic, and that a comprehensive understanding of its neurochemical basis may open new avenues to developing newer antipsychotic medications.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Etnofamacologia, ICBS, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite 500/202, 90050-170 Porto Alegre, RS, Brazil.

ABSTRACT
Managing schizophrenia has never been a trivial matter. Furthermore, while classical antipsychotics induce extrapyramidal side effects and hyperprolactinaemia, atypical antipsychotics lead to diabetes, hyperlipidaemia, and weight gain. Moreover, even with newer drugs, a sizable proportion of patients do not show significant improvement. Alstonine is an indole alkaloid identified as the major component of a plant-based remedy used in Nigeria to treat the mentally ill. Alstonine presents a clear antipsychotic profile in rodents, apparently with differential effects in distinct dopaminergic pathways. The aim of this study was to complement the antipsychotic profile of alstonine, verifying its effects on brain amines in mouse frontal cortex and striatum. Additionally, we examined if alstonine induces some hormonal and metabolic changes common to antipsychotics. HPLC data reveal that alstonine increases serotonergic transmission and increases intraneuronal dopamine catabolism. In relation to possible side effects, preliminary data suggest that alstonine does not affect prolactin levels, does not induce gains in body weight, but prevents the expected fasting-induced decrease in glucose levels. Overall, this study reinforces the proposal that alstonine is a potential innovative antipsychotic, and that a comprehensive understanding of its neurochemical basis may open new avenues to developing newer antipsychotic medications.

No MeSH data available.


Related in: MedlinePlus