Introduction to Aripiprazole

Aripiprazole is primarily used for the treatment of bipolar and schizophrenia. It differs from other atypical antipsychotics in that instead of antagonising the D₂ receptor it acts as a partial agonist. It is also associated with minimal weight gain by comparison to other atypical antipsychotics, it is believed this may be due to its 5-HT_2c agonism.[3]

Using Aripiprazole

Ways of Administration

Oral
IM Injection.

Dose

Column 1	Column 2
Threshold	0.25 mg
Light	2-5mg
Medium	10-15mg
Strong	15-30mg

Effects of Aripiprazole

Aripiprazole combinations

Recreational drug combinations with Aripiprazole

Concurrent use with stimulants (Amphetamines, MDMA, Cocaine) may reduce the efficacy of either or both agents. [4]

Dangerous interactions with Aripiprazole

No dangerous combinations with Aripiprazole have been added to this wiki yet.

Medication interactions with Aripiprazole

Strong CYP3A4 Inhibitors (e.g. itraconazole, clarithromycin) – Increases exposure of Aripiprazole.
Strong CYP2D6 Inhibitors (e.g. quinidine, fluoxetine, paroxetine) – Increases exposure of Aripiprazole.
Strong CYP3A4 Inducers (e.g. carbamazepine, rifampin) – Decreases exposure of Aripiprazole.
Antihypertensive drugs – May potentiate Antihypertensive drugs.
Benzodiazepines – Increased sedation.

Potentiators of Aripiprazole

No Potentiation combinations with Aripiprazole have been added to this wiki yet.

Different Uses for Aripiprazole

Aripiprazole is approved in the U.S. as an antipsychotic for schizophrenia and acute manic episodes in bipolar disorder. It is also used as adjunctive therapy in major depressive disorder, and may be of use in autism spectrum disorders and obsessive-compulsive disorder.

Pharmacology of Aripiprazole

General

Aripiprazole has a novel binding profile that differs from other atypical antispychotics in that it is a dopamine D₂ partial agonist, rather than an antagonist.[5]

It appears to show predominantly antagonist activity on postsynaptic D2 receptors and partial agonist activity on presynaptic D2 receptors. Aripiprazole is also a partial agonist of the D3 receptor.

Aripiprazole is also a partial agonist of the serotonin 5-HT1A receptor (intrinsic activity = 68%). It is a very weak partial agonist of the 5-HT2A receptor (intrinsic activity = 12.7%), and like other atypical antipsychotics, displays a functional antagonist profile at this receptor. The drug differs from other atypical antipsychotics in having higher affinity for the D2 receptor than for the 5-HT2A receptor. At the 5-HT2B receptor, aripiprazole acts as a potent inverse agonist. Unlike other antipsychotics, aripiprazole is a high-efficacy partial agonist of the 5-HT2C receptor (intrinsic activity = 82%) and with relatively weak affinity; this property may underlie the minimal weight gain seen in the course of therapy.

Targets, Enzymes, and Transporters

Targets

Target​
	Action​
D2	partial agonist
D3	partial agonist
D4	partial agonist
5HT1A	partial agonist
5HT2A	antagonist
5HT2C	partial agonist

Chemistry of Aripiprazole

Property​
	Values​
Systematic(IUPAC) name:	7-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy]-3,4-dihydro-1H-quinolin-2-one
Synonyms:	14597, OPC; 7-(4-(4-(2,3-dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone; Abilify; Aripiprazol; aripiprazole; OPC 14597; OPC-14597
Molecular Formula:	CXHYClNZOM...
Molar mass:	448.38538 g/mol.
CAS Registry Number:	129722-12-9
Melting Point:	No data
Boiling Point:	139.0-139.5 ℃+
Flash Point:	No data
Solubility:	<0.3 [ug/mL]
Additional data:
Notes:

[6]

Aripiprazole is a phenylpiperazine and is chemically related to nefazodone, etoperidone, and trazodone.

The Dangers of Aripiprazole

General Warnings

Cerebrovascular adverse reactions in elderly patients with dementia related psychosis.
Neuroleptic malignant syndrome
Tardive Dyskinesia
Metabolic changes – hyperglycaemia/diabetes mellitus, dyslipidemia, weight gain
Orthostatic hypotension
Leukopenia, Neutropenia and Argranulocytosis
Seizures/Convulsions – Use cautiously in patients with history of seizures or with conditions that lower the seizure threshold.
Potential for cognitive and motor impairment.
Suicide

Side Effects and Interactions

Potential Side Effects

Akathisia
Extrapyramidal disorder
Somnolence
Tremor
Sedation
Restlessness
Insomnia
Fatigue
Nausea
Blurred vision
Salivary hypersecretion
Dizziness
Constipation
Vomiting
Pyrexia
Drooling
Decreased appetite
Lethargy
Headache
Nasopharyngitis
Increased appetite

Potential Drug Interactions

Strong CYP3A4 Inhibitors (e.g. itraconazole, clarithromycin) – Increases exposure of Aripiprazole.
Strong CYP2D6 Inhibitors (e.g. quinidine, fluoxetine, paroxetine) – Increases exposure of Aripiprazole.
Strong CYP3A4 Inducers (e.g. carbamazepine, rifampin) – Decreases exposure of Aripiprazole.
Antihypertensive drugs – May potentiate Antihypertensive drugs.
Benzodiazepines – Increased sedation.

Mental Health Risks

Suicide

Risk of suicide is associated with schizophrenia and bipolar disorders. Close supervision of at risk patients should accompany therapy.

Legal Status of Aripiprazole

USA

Unscheduled but prescription only.

History of Aripiprazole

Aripiprazole was developed by Otsuka Pharmaceutical and its patent has since expired allowing the approval of generic versions since 2015.[7].

More Aripiprazole Sections and Information

Aripiprazole image Gallery: Post and view pictures of Aripiprazole.
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References

1. ^Otsuka Pharmaceutical. (2016). Ablify Product Information.
2. ^US Food and Drug Administration. (2015). Press Release - FDA approves first generic Abilify to treat mental illnesses.
3. ^ Zhang J. Y., Kowal D. M., Nawoschik S. P., Lou, Z., Dunlop J. Distinct functional profiles of aripiprazole and olanzapine at RNA edited human 5-HT2C receptor isoforms. Biochemical Pharmacology Volume 71, Issue 4, 14 February 2006, Pages 521–529.
4. ^Dean, A. (2006). Illicit drugs and drug interactions. Australian Pharmacist. 25 9. 684-689.
5. ^ Shapiro, D. A., Renock, S., Arrington, E., Chiodo, L. A., Liu, L., Sibley, D. R., … Mailman, R. (2003). Aripiprazole, A Novel Atypical Antipsychotic Drug with a Unique and Robust Pharmacology. Neuropsychopharmacology, 28(8), 1400-1411. doi:10.1038/sj.npp.1300203
6. ^ National Center for Biotechnology Information. Compound Summary for CID 60795
7. ^US Food and Drug Administration. (2015)