The following presentation discusses current thinking on the mechanism of action of aripiprazole
(scroll down to see a summary with images).
This image depicts aripiprazole binding to three different receptors: D2, 5HT1A, 5HT2A
1
What are the implications of D2 partial agonism? Aripiprazole binds to the D2 receptor with
the same affinity than dopamine, but has a lower intrinsic efficacy, so the response it
triggers is lower than dopamine but higher than an antagonist.
Aripiprazole as partial agonist: note that the signal is lower than dopamine but higher than an
antagonist
2
Positive symptoms of schizophrenia might be the result of an overactivation of the mesolimbic
pathway.
Aripiprazole reduces dopaminergic activity in the mesolimbic pathway through partial D2 agonism.
The dopamine theory of negative and cognitive symptoms suggests that there is a
hypofunction of dopaminergic neurotransmission in the mesocortical pathway.
3
Dopaminergic activity in the mesocortical pathway is thought to be reduced in schizophrenia
4
Aripiprazole is a partial agonist at D2 receptors.
It may act as an antipsychotic by:
o Lowering dopaminergic neurotransmission in the mesolimbic pathway.
o Enhancing dopaminergic activity in the mesocortical pathway.
o It has a lower risk of EPS and hyperprolactinemia than other antipsychotics.