Aripiprazole, a novel antipsychotic, is a high-affinity
partial agonist at human dopamine D2 receptors

Burris KD, Molski TF, Xu C, Ryan E,
Tottori K, Kikuchi T, Yocca FD, Molinoff PB.
Neuroscience Drug Discovery,
Bristol-Myers Squibb Pharmaceutical Research Institute,
5 Research Parkway, Wallingford, CT 06492, USA.
J Pharmacol Exp Ther 2002 Jul;302(1):381-9


Aripiprazole is the first next-generation atypical antipsychotic with a mechanism of action that differs from currently marketed typical and atypical antipsychotics. Aripiprazole displays properties of an agonist and antagonist in animal models of dopaminergic hypoactivity and hyperactivity, respectively. This study examined the interactions of aripiprazole with a single population of human D2 receptors to clarify further its pharmacologic properties. In membranes prepared from Chinese hamster ovary cells that express recombinant D2L receptors, aripiprazole bound with high affinity to both the G protein-coupled and uncoupled states of receptors. Aripiprazole potently activated D2 receptor-mediated inhibition of cAMP accumulation. Partial receptor inactivation using the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) significantly reduced the maximum effect of aripiprazole on inhibition of cAMP accumulation. This effect was seen with concentrations of EEDQ that did not alter the maximal inhibitory effect of dopamine. Consistent with the expected effects of a partial agonist, increasing concentrations of aripiprazole blocked the action of dopamine with maximal blockade equal to the agonist effect of aripiprazole alone. The efficacy of aripiprazole relative to that of dopamine varied from 25% in cells that lacked spare receptors for dopamine to 90% in cells with receptor reserve. These results, together with previous studies demonstrating partial agonist activity at serotonin 5-hydroxytryptamine (5-HT)1A receptors and antagonist activity at 5-HT2A receptors, support the identification of aripiprazole as a dopamine-serotonin system stabilizer. The receptor activity profile may underlie the unique activity of aripiprazole in animals and its antipsychotic activity in humans.
Aripiprazole: review
Schizophrenia: neuroleptics
Are atypicals antidepressants?
New antipsychotics: aripiprazole
Serotonin model of schizophrenia
Dopamine model of schizophrenia
Aripiprazole (Abilify, Abilitat): side-effects
Aripiprazole (Abilify, Abilitat) for bipolar mania
Aripiprazole (Abilify): prescribing information (PDF)
Quetiapine (Seroquel) and aripiprazole (Abilify, Abilitat)
Aripiprazole (Abilify, Abilitat): pharmacology and clinical use

and further reading

Future Opioids
BLTC Research
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Good Drug Guide

The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family