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Antipsychotics: The Essentials Module 2 Mechanism of Action of Aripiprazole

Flavio Guzmn, MD

Aripiprazole is a partial agonist that acts on mesolimbic and mesocortical dopamine pathways.

What is an partial agonist?

Aripiprazole as partial agonist

Partial agonism in the mesolimbic pathway

Dopamine Activity in Healthy Individuals


Dopaminergic neurotransmission
Maximal Activity Normal Activity

Basal Activity

log [drug]
Courtesy of Richard Mailman, modified from Mailman RB, Murthy V. Current pharmaceutical design 2010;16:488-501.

Schizophrenia: overactivity of the mesolimbic pathway


Dopaminergic neurotransmission
Maximal Activity Schizophrenia

Basal Activity

log [drug]
Courtesy of Richard Mailman, modified from Mailman RB, Murthy V. Current pharmaceutical design 2010;16:488-501.

Aripiprazole therapy
Dopaminergic neurotransmission
Maximal Activity Schizophrenia

Dotted sigm in the prese of dopamin

Basal Activity

log [drug]
Courtesy of Richard Mailman, modified from Mailman RB, Murthy V. Current pharmaceutical design 2010;16:488-501.

Partial agonism in the mesocortical pathway

Dopamine Activity in Normal Circumstances


Dopaminergic neurotransmission
Maximal Activity Normal Activity

Basal Activity log [drug]


Courtesy of Richard Mailman, modified from Mailman RB, Murthy V. Current pharmaceutical design 2010;16:488-501.

Dopamine System in Schizophrenia


Maximal Activity Normal Activity Schizophrenia Basal Activity

log [drug]
Courtesy of Richard Mailman, modified from Mailman RB, Murthy V. Current pharmaceutical design 2010;16:488-501.

Aripiprazole Therapy
Dopaminergic neurotransmission
Maximal Activity Normal Activity Schizophrenia Basal Activity log [drug]
Courtesy of Richard Mailman, modified from Mailman RB, Murthy V. Current pharmaceutical design 2010;16:488-501.

Aripiprazole effects on other dopamine pathways


Tuberoinfundibular Pathway Nigrostriatal Pathway

Less risk of hyperprolactinemia

Less risk of EPS

Other pharmacological properties

Key Points
Aripiprazole is a partial agonist at D2 receptors. It may act as an antipsychotic by:
Lowering dopaminergic neurotransmission in the mesolimbic pathway. Enhancing dopaminergic activity in the mesocortical pathway.

It has a lower risk of EPS and hyperprolactinemia than other antipsychotics