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Aripiprazole, A Drug that Displays Partial Agonism and Functional 
Selectivity

BACKGROUND: The treatment of schizophrenia is challenging due to the wide range of symptoms (positive, negative, cognitive) associated with the disease. Typical antipsychotics that antagonize D2 receptors are effective in treating positive symptoms, but extrapyramidal side-effects (EPS) are a common...

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Autores principales: Tuplin, Erin W., Holahan, Matthew R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bentham Science Publishers 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725548/
https://www.ncbi.nlm.nih.gov/pubmed/28412910
http://dx.doi.org/10.2174/1570159X15666170413115754
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author Tuplin, Erin W.
Holahan, Matthew R.
author_facet Tuplin, Erin W.
Holahan, Matthew R.
author_sort Tuplin, Erin W.
collection PubMed
description BACKGROUND: The treatment of schizophrenia is challenging due to the wide range of symptoms (positive, negative, cognitive) associated with the disease. Typical antipsychotics that antagonize D2 receptors are effective in treating positive symptoms, but extrapyramidal side-effects (EPS) are a common occurrence. Atypical antipsychotics targeting 5-HT2A and D2 receptors are more effective at treating cogni-tive and negative symptoms compared to typical antipsychotics, but these drugs also result in side-effects such as metabolic syndromes. OBJECTIVE: To identify evidence in the literature that elucidates the pharmacological profile of aripiprazole. METHODS: We searched PubMed for peer reviewed articles on aripiprazole and its clinical efficacy, side-effects, pharmacolo-gy, and effects in animal models of schizophrenia symptoms. RESULTS: Aripiprazole is a newer atypical antipsychotic that displays a unique pharmacological profile, including partial D2 agonism and functionally selective properties. Aripiprazole is effective at treating the positive symptoms of schizophrenia and has the potential to treat negative and cognitive symptoms at least as well as other atypical antipsychotics. The drug has a favorable side-effect profile and has a low propensity to result in EPS or metabolic syndromes. Animal models of schizophrenia have been used to determine the efficacy of aripiprazole in symptom management. In these instanc-es, aripiprazole resulted in the reversal of deficits in extinction, pre-pulse inhibition, and social withdrawal. Because aripipra-zole requires a greater than 90% occupancy rate at D2 receptors to be clinically active and does not produce EPS, this suggests a functionally selective effect on intracel-lular signaling pathways. CONCLUSION: A combination of factors such as dopamine system stabilization via partial agonism, functional selectivity at D2 receptors, and serotonin-dopamine system interaction may contribute to the ability of aripiprazole to successfully manage schizophrenia symptoms. This review examines these mechanisms of action to further clarify the pharmacological actions of aripiprazole.
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spelling pubmed-57255482018-05-01 Aripiprazole, A Drug that Displays Partial Agonism and Functional 
Selectivity Tuplin, Erin W. Holahan, Matthew R. Curr Neuropharmacol Article BACKGROUND: The treatment of schizophrenia is challenging due to the wide range of symptoms (positive, negative, cognitive) associated with the disease. Typical antipsychotics that antagonize D2 receptors are effective in treating positive symptoms, but extrapyramidal side-effects (EPS) are a common occurrence. Atypical antipsychotics targeting 5-HT2A and D2 receptors are more effective at treating cogni-tive and negative symptoms compared to typical antipsychotics, but these drugs also result in side-effects such as metabolic syndromes. OBJECTIVE: To identify evidence in the literature that elucidates the pharmacological profile of aripiprazole. METHODS: We searched PubMed for peer reviewed articles on aripiprazole and its clinical efficacy, side-effects, pharmacolo-gy, and effects in animal models of schizophrenia symptoms. RESULTS: Aripiprazole is a newer atypical antipsychotic that displays a unique pharmacological profile, including partial D2 agonism and functionally selective properties. Aripiprazole is effective at treating the positive symptoms of schizophrenia and has the potential to treat negative and cognitive symptoms at least as well as other atypical antipsychotics. The drug has a favorable side-effect profile and has a low propensity to result in EPS or metabolic syndromes. Animal models of schizophrenia have been used to determine the efficacy of aripiprazole in symptom management. In these instanc-es, aripiprazole resulted in the reversal of deficits in extinction, pre-pulse inhibition, and social withdrawal. Because aripipra-zole requires a greater than 90% occupancy rate at D2 receptors to be clinically active and does not produce EPS, this suggests a functionally selective effect on intracel-lular signaling pathways. CONCLUSION: A combination of factors such as dopamine system stabilization via partial agonism, functional selectivity at D2 receptors, and serotonin-dopamine system interaction may contribute to the ability of aripiprazole to successfully manage schizophrenia symptoms. This review examines these mechanisms of action to further clarify the pharmacological actions of aripiprazole. Bentham Science Publishers 2017-11 2017-11 /pmc/articles/PMC5725548/ /pubmed/28412910 http://dx.doi.org/10.2174/1570159X15666170413115754 Text en © 2017 Bentham Science Publishers https://creativecommons.org/licenses/by-nc/4.0/legalcode This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
spellingShingle Article
Tuplin, Erin W.
Holahan, Matthew R.
Aripiprazole, A Drug that Displays Partial Agonism and Functional 
Selectivity
title Aripiprazole, A Drug that Displays Partial Agonism and Functional 
Selectivity
title_full Aripiprazole, A Drug that Displays Partial Agonism and Functional 
Selectivity
title_fullStr Aripiprazole, A Drug that Displays Partial Agonism and Functional 
Selectivity
title_full_unstemmed Aripiprazole, A Drug that Displays Partial Agonism and Functional 
Selectivity
title_short Aripiprazole, A Drug that Displays Partial Agonism and Functional 
Selectivity
title_sort aripiprazole, a drug that displays partial agonism and functional 
selectivity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725548/
https://www.ncbi.nlm.nih.gov/pubmed/28412910
http://dx.doi.org/10.2174/1570159X15666170413115754
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