Aripiprazole
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Aripiprazole
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| Systematic (IUPAC) name | |
| 7-[4-[4-(2,3-dichlorophenyl) piperazin-1-yl]butoxy]- 3,4-dihydro-1H-quinolin-2-one |
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| Identifiers | |
| CAS number | |
| ATC code | N05 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C23H27Cl2N3O2 |
| Mol. mass | 448.385 |
| SMILES | & |
| Pharmacokinetic data | |
| Bioavailability | 87% |
| Metabolism | liver |
| Half life | 75h (active metabolite : 94h) |
| Excretion | feces and urine |
| Therapeutic considerations | |
| Licence data |
, |
| 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.
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[edit] 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-HT1A receptor, and like the other atypical antipsychotics displays an antagonist profile at the 5-HT2A receptor. Aripiprazole has moderate affinity for histamine and alpha-adrenergic receptors, and no appreciable affinity for cholinergic muscarinic receptors.
[edit] 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.[2]
[edit] 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.
[edit] Dosage forms
Aripiprazole is available in 1mg, 2mg, 5mg, 10mg, 15mg, 20mg, and 30mg tablets.[3]
Aripiprazole is also available as 10mg and 15mg orodispersible tablets, 1mg/1ml solution and 7.5mg/ml injection (for rapid tranquilisation)
[edit] 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.
[edit] Side effects
Common side effects: Akathisia, headache, unusual tiredness or weakness, nausea, vomiting, an uncomfortable feeling in the stomach, constipation, 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.
[edit] See also
[edit] References
Lawler CP et al. (1999). "Interactions of the novel antipsychotic aripiprazole (OPC-14597) with dopamine and serotonin receptor subtypes". Neuropsychopharmacology 20: 612-27. PMID 10327430. Fulltext
Shapiro DA et al. (2003). "Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology". Neuropsychopharmacology 28: 1400-1411.
Urban JD et al.. "Aripiprazole has functionally selective actions at dopamine D2 receptor-mediated signaling pathways". Neuropsychopharmacol. 32:. PMID 16554739.
Urban JD et al. (2007). "Functional selectivity and classical concepts of quantitative pharmacology". J Pharmacol Exp Ther 320: 1-13. PMID 16803859.
- ^ FDA OKs Abilify for Depression
- ^ (WO/2007/035348) NANOPARTICULATE ARIPIPRAZOLE FORMULATIONS
- ^ 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
[edit] External links
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