Dopamine partial agonists: a discrete class of antipsychotics

Area of Science:

• Psychopharmacology
• Neuroscience
• Clinical Psychiatry

Background:

• Three dopamine D2 partial agonists (aripiprazole, brexpiprazole, cariprazine) are currently marketed worldwide.
• These agents share key pharmacological and clinical characteristics, distinguishing them from dopamine D2 antagonists.

Purpose of the Study:

• To delineate the shared properties of dopamine D2 partial agonists.
• To establish dopamine D2 partial agonists as a distinct therapeutic class.

Main Methods:

• Pharmacological profiling of dopamine D2 partial agonists.
• Clinical efficacy and tolerability assessment.
• Comparative analysis against dopamine D2 antagonists.

Main Results:

• Dopamine D2 partial agonists exhibit 5HT2 antagonism and D3/5HT1A partial agonism with minimal adrenergic, anticholinergic, or antihistaminic activity.
• They demonstrate efficacy as antipsychotics with antimanic and antidepressant properties, generally well-tolerated with low incidence of akathisia, insomnia, prolactin increase, weight gain, and metabolic effects.
• These agents may have a lower risk of tardive dyskinesia and are potentially preferred by patients over dopamine antagonists.

Conclusions:

• Dopamine D2 partial agonists constitute a unique class of antipsychotics due to their shared pharmacological and clinical profiles.
• Their distinct properties necessitate consideration as a separate therapeutic category from dopamine D2 antagonists.