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Aripiprazole
Systematic (IUPAC) name
7-[4-[4-(2,3-dichlorophenyl) piperazin-1-yl]butoxy]- 3,4-dihydro-1H-quinolin-2-one
Identifiers
CAS number	129722-12-9
ATC code	N05AX12
PubChem	60795
DrugBank	APRD00638
Chemical data
Formula	C23H27Cl2N3O2
Mol. mass	448.385
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	87%
Metabolism	liver
Half life	75h (active metabolite : 94h)
Excretion	feces and urine
Therapeutic considerations
Licence data	EU, US
Pregnancy cat.	C (USA)
Legal status	℞ Prescription only
Routes	oral tablets or parenteral solution

Aripiprazole (ay-ree-PIP-ray-zole) (sold as Abilify) was approved by the Food and Drug Administration (FDA) on November 15, 2002 for the treatment of schizophrenia, the sixth atypical antipsychotic medication of its kind. More recently it received FDA approval for the treatment of acute manic and mixed episodes associated with bipolar disorder, as well as treatment of depression^[1]. Aripiprazole was developed by Otsuka in Japan; in the U.S., Otsuka America markets the drug jointly with Bristol-Myers Squibb.

Contents 1 Pharmacology 2 Pharmacokinetics 3 Metabolism 4 Dosage forms 5 Warnings about medications with similar names 6 Side effects 7 See also 8 References 9 External links

Pharmacology

Aripiprazole's mechanism of action is different from the other FDA-approved atypical antipsychotics (e.g., clozapine, olanzapine, quetiapine, ziprasidone, and risperidone). Although it is commonly believed that aripiprazole appears to mediate its antipsychotic effects due to partial agonism at the D₂ dopamine receptor, it is more likely that the primary mechanism of action is functional selectivity at the D₂ receptor. In either case, some type of differential modulation of dopaminergic activity may occur in mesolimbic, mesocortical, and basal ganglia target fields in the brain. In addition to its functional selectivity at the D₂ receptor, aripiprazole is also a partial agonist at the 5-HT_1A receptor, and like the other atypical antipsychotics displays an antagonist profile at the 5-HT_2A receptor. Aripiprazole has moderate affinity for histamine and alpha-adrenergic receptors, and no appreciable affinity for cholinergic muscarinic receptors.

Its mechanism of action makes aripiprazole a useful adjunct in the short-term treatment of psychosis associated with methylenedioxymethampetamine ( ecstasy ) abuse. It as also useful in the treatment of psychoses generated by compounds similar to ecstasy and its derivatives. It is not advised in the treatment of the chemically similar, but non-derivative, paramethoxymethamphetamine (PMA or Dr. Death). ^[2]

Pharmacokinetics

Aripiprazole displays linear kinetics and has an elimination half-life of approximately 75 hours.  Steady-state plasma concentrations are achieved in about 14 days.  Cmax (maximum plasma concentration) is achieved 3-5 hours after oral dosing.  Bioavailability of the oral tablets is about 90% and the drug undergoes extensive hepatic metabolization (dehydrogenation, hydroxylation, and N-dealkylation). Its active major metabolite is dehydro-aripiprazole, whose elimination half-life is about 94 hours. The parenteral drug is excreted only in traces, and its metabolites, active or not, are excreted via feces and urine.^[3]

Metabolism

Aripiprazole is metabolized by the Cytochrome P450 isoenzymes 3A4 and 2D6.  Accordingly, coadministration of aripiprazole with medications that may inhibit (e.g. paroxetine, fluoxetine) or induce (e.g. carbamazepine) these metabolic enzymes may increase or decrease, respectively, plasma concentrations of aripiprazole. Where there is coadministration of an interfering drug, measurement of plasma aripiprazole levels may be useful, with target concentrations of 150-300µg/L being suggested for aripiprazole (pre-dose sample) and dehydroaripiprazole at approximately 40% of the aripiprazole level.

Dosage forms

Aripiprazole is available in 1mg, 2mg, 5mg, 10mg, 15mg, 20mg, and 30mg tablets.^[4]Aripiprazole is also available as 10mg and 15mg orodispersible tablets, 1mg/1ml solution and 7.5mg/ml injection (for rapid tranquilisation)

Warnings about medications with similar names

Warning flags are raised by the drug's name: the '-prazole' suffix incorrectly associates the drug with the proton pump inhibitors (such as omeprazole, pantoprazole, and lansoprazole), that are used to treat peptic ulcer disease. However, aripiprazole is in an entirely different class of drugs, and can provoke unnecessary side effects when incorrectly prescribed for peptic ulcer disease.

Side effects

Common side effects: Akathisia, headache, unusual tiredness or weakness, nausea, vomiting, an uncomfortable feeling in the stomach, constipation, weight gain, light-headedness, trouble sleeping, restlessness, sleepiness, shaking, and blurred vision.

Uncommon side effects: Uncontrollable twitching or jerking movements, tremors and seizure. Some people may feel dizzy, especially when getting up from a lying or sitting position, or may experience a fast heart rate.

Rare side effects: Combination of fever, muscle stiffness, faster breathing, sweating, reduced consciousness, and sudden change in blood pressure and heart rate (neuroleptic malignant syndrome).

Very rare side effects: Allergic reaction (such as swelling in the mouth or throat, itching, rash), increased production of saliva, speech disorder, nervousness, agitation, fainting, reports of abnormal liver test values, inflammation of the pancreas, muscle pain, weakness, stiffness, or cramps.

While taking aripiprazole some elderly patients with dementia have suffered from stroke or 'mini' stroke. Other patients may experience high blood sugar or the onset or worsening of diabetes.

See also

• Tardive dysphrenia

References

• Lawler CP et al. (1999). "Interactions of the novel antipsychotic aripiprazole (OPC-14597) with dopamine and serotonin receptor subtypes". Neuropsychopharmacology 20: 612–27. doi:10.1016/S0893-133X(98)00099-2. PMID 10327430.  Fulltext
• Shapiro DA et al. (2003). "Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology". Neuropsychopharmacology 28: 1400–1411. doi:10.1038/sj.npp.1300203. 
• Urban JD et al. (2007). "Aripiprazole has functionally selective actions at dopamine D2 receptor-mediated signaling pathways". Neuropsychopharmacol. 32:: 67–77, 2007. doi:10.1038/sj.npp.1301071. PMID 16554739. 
• Urban JD et al. (2007). "Functional selectivity and classical concepts of quantitative pharmacology". J Pharmacol Exp Ther 320: 1–13. doi:10.1124/jpet.106.104463. PMID 16803859. 

1. ^ FDA OKs Abilify for Depression
2. ^ AJ Giannini. Drugs of Abuse--Second Edition. Los Angeles, Practice Management Information Corp., 1997.
3. ^ (WO/2007/035348) NANOPARTICULATE ARIPIPRAZOLE FORMULATIONS
4. ^ U.S. Food and Drug Administration Approves ABILIFY(R) (aripiprazole) for the Acute Treatment of Manic and Mixed Episodes Associated With Bipolar I Disorder in Pediatric Patients (10 to 17 Years of Age) - Forbes.com

External links

• Abilify - The Internet Drug Database
• Abilify on Epocrates Drug Lookup
• Abilify website
• drug label

  v • d • e Psycholeptics: antipsychotics - primarily dopamine antagonists (N05A) Typical Phenothiazine Chlorpromazine • Fluphenazine • Mesoridazine • Periciazine • Perphenazine • Prochlorperazine • Promazine • Thioridazine/Sulforidazine • Trifluoperazine • Triflupromazine Indoles Molindone Butyrophenones Azaperone, Benperidol, Bromperidol, Droperidol, Haloperidol, Trifluperidol Thioxanthenes Flupentixol, Chlorprothixene, Thiothixene, Zuclopenthixol Diphenylbutylpiperidines Fluspirilene, Penfluridol, Pimozide Other Loxapine Atypical Serotonin antagonists Butyrophenones Melperone Indoles Sertindole, Ziprasidone Diazepines/oxazepines/thiazepines Clozapine, Olanzapine, Quetiapine Other Aripiprazole, Asenapine, Iloperidone, Mosapramine, Paliperidone, Perospirone, Risperidone, Zotepine Benzamides Sulpiride, Remoxipride, Amisulpride

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• This page was last modified on 27 August 2008, at 19:00.

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