What is the mechanism of action of Abilify (Aripiprazole)?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: April 13, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Aripiprazole (Abilify) works through a unique mechanism called partial dopamine agonism, acting as a partial agonist at dopamine D2 and D3 receptors and as a partial agonist at serotonin 5-HT1A receptors and an antagonist at 5-HT2A receptors. This mechanism is distinct from traditional antipsychotics, which simply block dopamine receptors, and is believed to contribute to its effectiveness in treating schizophrenia and other conditions with fewer extrapyramidal side effects 1. The medication's ability to reduce dopamine activity in overactive pathways while increasing dopamine activity in underactive pathways creates a stabilizing effect, making it useful for both positive and negative symptoms of schizophrenia. Some key points about aripiprazole's mechanism include:

  • Partial dopamine agonism at D2 and D3 receptors
  • Partial agonism at serotonin 5-HT1A receptors
  • Antagonism at 5-HT2A receptors
  • Ability to reduce dopamine activity in overactive pathways and increase dopamine activity in underactive pathways
  • Effectiveness in treating schizophrenia and other conditions with fewer extrapyramidal side effects compared to typical antipsychotics 1. Overall, aripiprazole's unique mechanism of action makes it a valuable treatment option for a range of psychiatric conditions.

From the FDA Drug Label

The mechanism of action of aripiprazole in schizophrenia is unclear. However, the efficacy of aripiprazole in the listed indications could be mediated through a combination of partial agonist activity at D 2 and 5-HT 1A receptors and antagonist activity at 5-HT 2A receptors.

The mechanism of action of Abilify (Aripiprazole) is not fully understood, but it is believed to involve:

  • Partial agonist activity at D2 and 5-HT1A receptors
  • Antagonist activity at 5-HT2A receptors 2

From the Research

Mechanism of Action of Abilify (Aripiprazole)

  • Aripiprazole is an atypical antipsychotic drug that exhibits partial agonism at dopamine (D2) and 5-HT1A receptors, as well as antagonistic action at 5-HT2A receptors 3, 4.
  • The drug has a unique pharmacologic profile, which includes high affinity for dopamine D2 and D3, serotonin 5-HT1A and 5-HT2A receptors, moderate affinity for dopamine D4, serotonin 5-HT2C and 5-HT7, alpha1-adrenergic and histamine H1 receptors 5.
  • Aripiprazole's mechanism of action is thought to involve the stabilization of the dopamine system via partial agonism, functional selectivity at D2 receptors, and serotonin-dopamine system interaction 6.
  • Recent studies have suggested that aripiprazole acts as a selective dopamine D2 receptor partial agonist, and does not affect 5-HT receptors at therapeutic doses 7.

Key Features of Aripiprazole's Mechanism

  • Partial agonism at dopamine D2 receptors, which contributes to its efficacy in treating positive symptoms of schizophrenia 3, 4.
  • Functional selectivity at D2 receptors, which may contribute to its low propensity to result in extrapyramidal side-effects (EPS) or metabolic syndromes 6.
  • Interaction with the serotonin-dopamine system, which may contribute to its ability to manage schizophrenia symptoms 6.

Pharmacodynamics and Pharmacokinetics

  • Aripiprazole has a mean elimination half-life of about 75 hours, and steady-state concentrations are attained within 14 days of dosing 5.
  • The drug has a favorable side-effect profile, with a low propensity to result in EPS or metabolic syndromes 3, 4, 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.