Dopamine partial agonists: a discrete class of antipsychotics

Abstract

Worldwide, there are now three marketed dopamine D2 partial agonists: aripiprazole, brexpiprazole and cariprazine. These three drugs share a number of properties other than their action at D2 receptors. Pharmacologically, they are 5HT2 antagonists and D3 and 5HT1A partial agonists but with little or no alpha-adrenergic, anticholinergic or antihistaminic activity. They also share a long duration of action. Clinically, D2 partial agonists are effective antipsychotics and generally have useful antimanic and antidepressant activity. They are usually well tolerated, causing akathisia and insomnia only at the start of treatment, and are non-sedating. These drugs also share a very low risk of increased prolactin and of weight gain and accompanying metabolic effects. They may also have a relatively low risk of tardive dyskinesia. There is some evidence that they are preferred by patients to dopamine antagonists. Individual dopamineD2 partial agonists have much in common and as a group they differ importantly from dopamine D2 antagonists. Dopamine D2 partial agonists should be considered a distinct class of antipsychotics.

Key points

• D2 partial agonists share many pharmacological and clinical properties

• D2 partial agonists differ in several important respects from D2 antagonists

• D2 partial agonists should be considered a discrete class of antipsychotics

Keywords:

• D2 partial angonists
• antipsychotics
• aripiprazole
• brexpiprazole
• cariprazine

Disclosure statement

DT has received speaker honoraria from Janssen, Servier, Otsuka and Lundbeck. Research funding has been received from Janssen, Lundbeck and BMS. LH has received fees for presentations and advisory board attendance from Takeda, Recordati, Lundbeck and Sunovion. LH is medical director for Healios and Plast-IQ. RC has received speaker or chair fees from Janssen Cilag, Recordati, Lundbeck, Otsuka, Myogenes, Psych genetic Ltd, CNX therapeutics and for advisory board attendance from Boehringer-Ingelheim and Recordati. GR has received speaker honoraria and/or advisory board attendance from Boehringer-Ingelheim, Kang Hong, Lundbeck, Otsuka, Recordati and Sumitomo. JG has received fees from Recordati for chairing educational meetings. SP has received fees from Janssen, Recordati, Sunovion, CNX therapeutics, ROVI Biotech.