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aripiprazole + lamotrigine + quetiapine + valproic acid

Development stage
Unknown
Lead developer
Bristol Myers Squibb
Modality
Small Molecules
Administration
Oral, Intramuscular, Intravenous
01

Overview

This is a combination therapy consisting of four distinct pharmaceutical agents commonly used in the management of mood disorders, particularly bipolar disorder and schizoaffective disorder. The components are: - **Aripiprazole**: An atypical antipsychotic that acts as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors, and as an antagonist at serotonin 5-HT2A receptors. It is primarily used for schizophrenia, bipolar I disorder (manic or mixed episodes), adjunctive treatment of major depressive disorder, irritability associated with autistic disorder, and Tourette's disorder[3][5]. - **Lamotrigine**: An anticonvulsant that stabilizes neuronal membranes by inhibiting voltage-sensitive sodium channels, thereby modulating presynaptic release of excitatory amino acids such as glutamate. It is indicated for epilepsy (various seizure types) and maintenance treatment of bipolar I disorder to delay mood episodes[1][3][5]. - **Quetiapine**: Another atypical antipsychotic with antagonistic activity at multiple neurotransmitter receptors including serotonin 5-HT2A and dopamine D2. It is approved for schizophrenia, acute manic or mixed episodes in bipolar I disorder (as monotherapy or adjunct), depressive episodes in bipolar depression, and as adjunctive therapy in major depressive disorder[6][7][8]. - **Valproic acid** (also known as sodium valproate): A broad-spectrum anticonvulsant that increases brain concentrations of gamma aminobutyric acid (GABA) by inhibiting its degradation; it also has effects on voltage-gated sodium channels. Indications include epilepsy/seizure disorders, acute mania in bipolar I disorder, migraine prophylaxis[6][7]. The rationale behind this combination lies in their complementary mechanisms—providing synergistic mood-stabilizing effects while targeting both manic/mixed states and depressive symptoms seen in complex psychiatric conditions like refractory or rapid-cycling bipolar disorders.

02

Targets

HTR2A (Serotonin receptor 5-HT2A)NaV (Voltage-gated sodium channels)HTR1A (Serotonin receptor 1A (5-hydroxytryptamine receptor 1A))HDAC (HDAC family)DRD2 (Dopamine D2 Receptor)DRD3 (Dopamine receptor D3)

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