VRAYLAR is thought to have adaptive receptor activity as a partial agonist to help modulate dopamine and serotonin1

Mechanism of action

The mechanism of action of VRAYLAR is unknown. The efficacy of VRAYLAR is thought to be mediated through a combination of partial agonist activity at central dopamine D2 and serotonin 5-HT1A receptors and antagonist activity at serotonin 5-HT2A receptors.1

LOW

May act as an agonist to increase signaling when neurotransmitters are low2

Dial showing dopamine and serotonin activity with partial agonism.

HIGH

May act as an antagonist to decrease signaling when neurotransmitters are high2

VRAYLAR is the only partial agonist approved for MDD (adjunctive) and bipolar I depressive and acute manic or mixed episodes.1

VRAYLAR is indicated in adults as adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD), for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression), for the acute treatment of manic or mixed episodes associated with bipolar I disorder, and for the treatment of schizophrenia.1

VRAYLAR is thought to act on a variety of receptors, including dopamine and serotonin1,3,4

Pharmacodynamics

Chart showing VRAYLAR receptor binding affinity.

VRAYLAR is shown to have a higher dopamine D3 binding affinity than that of endogenous dopamine5

VRAYLAR demonstrated up to ~8-fold greater in vitro affinity for dopamine D3 vs D2 receptors1

The clinical significance of the in vitro data is unknown.

Ki (inhibitory constant) value represents the binding strength between a medication and a specific receptor.

The smaller the Ki value, the greater the binding affinity to that receptor.

No appreciable affinity for cholinergic muscarinic receptors (IC50>1000 nM).

*dopamine D3 Ki value (nM): 0.085, dopamine D2L Ki value (nM): 0.49, dopamine D2S Ki value (nM): 0.69, serotonin 5-HT2B Ki value (nM): 0.58, serotonin 5-HT1A Ki value (nM): 2.6.

†serotonin 5-HT2A Ki value (nM): 18.8, histamine H1 Ki value (nM): 23.2.

‡serotonin 5-HT2C Ki value (nM): 134, α1A-adrenergic Ki value (nM): 155.

In MDD, VRAYLAR can provide complementary actions to antidepressants by binding to a variety of receptors1

Pyramid diagram showing pharmacodynamic receptor binding.

Not an exhaustive list of the receptors that are thought to be bound by cariprazine.

§The activity of these compounds is based on in vitro data. The clinical significance of the in vitro data is unknown.

Review dosing

MDD=major depressive disorder; nM=nanomolar.