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 |
| Pharmacokinetic data | |
| Bioavailability | 90% |
| Metabolism | liver |
| Half life | 75h (active metabolite : 94h) |
| Excretion | feces and urine |
| Therapeutic considerations | |
| Licence data |
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| Pregnancy cat. |
C (USA) |
| Legal status |
℞ Prescription only |
| Routes | oral tablets or drink |
Aripiprazole (produced by Otsuka Pharmaceutical Co,. Ltd. and sold as Abilify®) is the sixth and most recent of the atypical antipsychotic medications to be approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia. It has also recently received FDA approval for the treatment of acute manic and mixed episodes associated with bipolar disorder.
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[edit] Pharmacology
Aripiprazole possesses a novel mechanism of action when compared to the other FDA approved atypical antipsychotics (i.e. clozapine, olanzapine, quetiapine, ziprasidone, and risperidone). Aripiprazole appears to mediate its antipsychotic effects primarily by partial agonism at the D2 receptor. Partial agonism at D2 receptors has been shown to modulate dopaminergic activity in areas where dopamine activity may be high or low, such as the mesolimbic and mesocortical areas of the schizophrenic brain, respectively. In addition to partial agonist activity at the D2 receptor, aripiprazole is also a partial agonist at the 5-HT1A receptor, and like the other atypical antipsychotics, aripiprazole 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 with an elimination half-life of approximately 75 hours. Accordingly, steady state plasma concentrations are achieved in about 14 days. Cmax (maximum plasma concentration) is achieved in 3-5 hours after oral dosing. The bioavailabilty of the oral tablets is about 90%. The drug undergoes extensive hepatic metabolization (dehydrogenation, hydroxylation, and N-dealkylation). The active major metabolite is dehydro-aripiprazole with an elimination half-life of about 94 hours. The parent drug is excreted only in traces and the metabolites, whether active or not, are excreted via feces and urine.
[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.
[edit] Adverse events
Adverse events reported in the package insert for aripiprazole include headache, nausea, vomiting, somnolence, insomnia, and akathisia. While Otsuka Pharmaceuticals has reported that the overall risk of EPS (Extrapyramidal Symptoms) is low with aripiprazole, they have separated akathisia from their analysis. With this adverse event included - the risk for EPS become substantial, similar to that of Zyprexa or Risperdal.The risk of tardive dyskinesia with prolonged aripiprazole use is unclear.
[edit] Dosage forms
Aripiprazole is available in 2mg, 5mg, 10mg, 15mg, 20mg, and 30mg tablets.
[edit] Warnings about medications with similar names
A warning has gone out recently because of this drug's name. The '-prazole' ending of this drug name makes this drug sound like it is one of the proton pump inhibitors (such as omeprazole, pantoprazole, lansoprazole) which are used in treating peptic ulcer disease. However, aripiprazole and these drugs are in an entirely different class of drugs altogether and confusing the two can lead to some unnecessary side effects.
Aripiprazole was develeloped by Otsuka Pharmaceutical Co., Ltd and is manufactured by the Bristol Myers Squibb pharmaceutical company (NYSE: BMY).
Aripiprazole was approved by the FDA on November 15, 2002.
[edit] Side effects
Common side effects: 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.
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. Some patients may experience high blood sugar, or the onset or worsening of diabetes.
