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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

Serotonin (5-HT) and its metabolite (5HIAA) in mouse frontal cortex (a) and in striatum (b) Mean ± SD. *P < .05, **P < .01 when compared with saline, Independent t-test.
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fig3: Serotonin (5-HT) and its metabolite (5HIAA) in mouse frontal cortex (a) and in striatum (b) Mean ± SD. *P < .05, **P < .01 when compared with saline, Independent t-test.

Mentions: The effects of alstonine on brain amines are shown in Figures 2 and 3. DA levels were decreased (t = 4.96, P < .01) in frontal cortex (Figure 2(a)), with a concomitant increase in DOPAC (t = −2.22, P < .05) and no change in HVA. DOPAC levels were also increased (t = −3.62, P < .01) in the striatum (Figure 2(b)), without changes in DA or HVA. 5HT levels were increased only in the frontal cortex (t = −3.74, P < .05), whereas increases in 5-HIAA were seen in frontal cortex (t = −2.68, P < .01, Figure 3(a)) and striatum (t = −2.5, P < .05, Figure 3(b)).


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)

Serotonin (5-HT) and its metabolite (5HIAA) in mouse frontal cortex (a) and in striatum (b) Mean ± SD. *P < .05, **P < .01 when compared with saline, Independent t-test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: Serotonin (5-HT) and its metabolite (5HIAA) in mouse frontal cortex (a) and in striatum (b) Mean ± SD. *P < .05, **P < .01 when compared with saline, Independent t-test.
Mentions: The effects of alstonine on brain amines are shown in Figures 2 and 3. DA levels were decreased (t = 4.96, P < .01) in frontal cortex (Figure 2(a)), with a concomitant increase in DOPAC (t = −2.22, P < .05) and no change in HVA. DOPAC levels were also increased (t = −3.62, P < .01) in the striatum (Figure 2(b)), without changes in DA or HVA. 5HT levels were increased only in the frontal cortex (t = −3.74, P < .05), whereas increases in 5-HIAA were seen in frontal cortex (t = −2.68, P < .01, Figure 3(a)) and striatum (t = −2.5, P < .05, Figure 3(b)).

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