Title:Aripiprazole, A Drug that Displays Partial Agonism and Functional Selectivity
Volume: 15
Issue: 8
Author(s): Erin W Tuplin *Matthew R Holahan*
Affiliation:
- Department of Neuroscience, Faculty of Science, Carleton University, 3414 Herzberg, 1125 Colonel By Drive, Ottawa, K1S 5B6, ON,Canada
- Department of Neuroscience, Faculty of Science, Carleton University, 3414 Herzberg, 1125 Colonel By Drive, Ottawa, K1S 5B6, ON,Canada
Keywords:
Dopamine receptors, schizophrenia, antipsychotics, partial agonism, functional selectivity, serotonin receptors,
MK-801
Abstract: 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 cognitive 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.s.
Methods: We searched PubMed for peer reviewed articles on aripiprazole and its clinical efficacy,
side-effects, pharmacology, 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 instances, aripiprazole resulted in the reversal of deficits in extinction, pre-pulse
inhibition, and social withdrawal. Because aripiprazole 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 intracellular 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.
