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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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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Bentham Science Publishers
2017
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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. |
format | Online Article Text |
id | pubmed-5725548 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Bentham Science Publishers |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT tuplinerinw aripiprazoleadrugthatdisplayspartialagonismandfunctionalselectivity AT holahanmatthewr aripiprazoleadrugthatdisplayspartialagonismandfunctionalselectivity |