1. Antipsychotics: The Essentials Module 2 Mechanism of Action of Aripiprazole
Flavio Guzmán, MD

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

3. What is an partial agonist?

4. Aripiprazole as partial agonist

5. Partial agonism in the mesolimbic pathway

6. 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:

7. 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:

8. Aripiprazole therapy
Dotted sigmoidal line: actions of partial agonist in the presence of endogenous concentrations of dopamine.
Dopaminergic neurotransmission
Maximal Activity
Schizophrenia
Basal Activity
log [drug]
Courtesy of Richard Mailman, modified from Mailman RB, Murthy V. Current pharmaceutical design 2010;16:

9. Partial agonism in the mesocortical pathway

10. 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:

11. 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:

12. 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:

13. Aripiprazole effects on other dopamine pathways
Tuberoinfundibular Pathway
Nigrostriatal Pathway
Less risk of hyperprolactinemia
Less risk of EPS

14. Other pharmacological properties

15. 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