Schizophrenia aripiprazole

Aripiprazole was formulated in the early 1980s to function as a potential dopamine modulator, with both antagonist and agonist activity at the D2 receptor. It is the first D2 partial agonist available for the treatment of schizophrenia and is sometimes referred to as a third-generation antipsychotic. This novel mechanism is... 

Chan, H. Y. etal. (2007). Efficacy and safety of aripiprazole in the acute treatment of schizophrenia in Chinese patients with risperidone as an active control a randomized trial. /. Clin. Psychiatry, 68, 29-36. 

We prefer low doses of atypical antipsychotics as a first-line treatment. In this way, the threat of extrapyramidal symptoms is largely avoided without having to use a second anticholinergic medication to offset antipsychotic side effects. Risperidone 0.25-0.5mg/day, olanzapine 2.5mg/day, quetiapine 25mg/day, ziprasidone 20mg/day, or aripiprazole 2.5-5mg/day are reasonable starting doses. The typically higher doses used to treat schizophrenia are usually not necessary. 

Antipsychotics in a few small studies have been shown to be helpful. To date this research is limited to typical antipsychotics. Nevertheless, the excellent track record of atypical antipsychotics in treating schizophrenia and the lower burden of side effects lead us to recommend atypical antipsychotics as a first-line treatment for STPD as well. Low doses of risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole are all reasonable options. If no therapeutic effect is observed, doses should be increased. 

Swainston T, Perry CM. Aripiprazole a review of its use in schizophrenia and schizoaffective disorder. Drugs 2004 64 1715-36. 

Maintenance Evaluation of patients with schizophrenia who had been stable on other antipsychotic medications for periods of 3 months or longer, were discontinued from those medications, and were then administered aripiprazole 15 mg/day and who were observed for relapse for up to 26 weeks demonstrated a benefit of such maintenance treatment. Periodically reassess patients to determine the need for maintenance treatment. 

Aripiprazole has been approved for treatment of schizophrenia and acute manic or mixed episodes in bipolar disorder. This medication is also indicated for maintenance treatment in bipolar I disorder. The recommended starting and target dose for aripiprazole in patients with schizophrenia is 10 or 15 mg/day. This is a once-daily dose, and patients can take the medication with or without food. Although this medication has been shown to be effective in doses ranging from 10 to 30 mg/day, doses higher than 10-15 mg have not been shown to be more effective than 10- to 15-mg doses in patients with schizophrenia. The recommended starting dose for treatment of an acute manic or mixed episode is 30 mg the recommended dose for maintenance treatment in stable patients is 15 mg/day. The elimination half-life is 75 hours, and steady-state concentrations are reached within 2 weeks. Therefore, dose adjustments are recommended every 2 weeks, to allow time for clinical assessments of the medication s effects to be observed at steady-state concentration. Peak plasma concentrations occur within 3-5 hours. At equivalent doses, the plasma concentrations of aripiprazole from the solution were higher compared with plasma concentrations associated with the tablet form. 

These findings have been incorporated into the dopamine hypothesis of schizophrenia. However, additional factors complicate interpretation of dopamine receptor data. For example, dopamine receptors exist in both high- and low-affinity forms, and it is not known whether schizophrenia or the antipsychotic drugs alter the proportions of receptors in these two forms. The fact that aripiprazole shows partial agonism at D2 and 5-HT1A receptors in preclinical studies suggests that the proportions of several receptors in their various affinity states may prove clinically important. 

Aripiprazole Blockade of 5HT2A receptors > blockade of D2 receptors Some a blockade (clozapine, risperidone, ziprasidone) and M-receptor blockade (clozapine, olanzapine) variable receptor blockade (all) Schizophrenia—improve both positive and negative symptoms bipolar disorder (olanzapine or risperidone adjunctive with lithium) agitation in Alzheimer s and Parkinson s (low doses) major depression (aripiprazole) Toxicity Agranulocytosis (clozapine), diabetes (clozapine, olanzapine), hypercholesterolemia (clozapine, olanzapine), hyperprolactinemia (risperidone), QT prolongation (ziprasidone), weight gain (clozapine, olanzapine)... 

Bhattacharjee J, El-Sayeh HG Aripiprazole versus typical antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev 2008 16 (3) CD006617. 

Kane JM, Carson WH, Saha AR, Saha AR, McQuade RD, Ingenito GG, Zumbroff DL, Ali MW (2002) Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiat 63 763-71 Kasper S, Lerman MN, McQuade RD, Saha A, Carson WH, Ali M, Archibald D, Ingenito G, Marcus R, Pigott T (2003). Efficacy and safety of aripiprazole vs. haloperidol for long-term maintenance treatment following acute relapse of schizophrenia. Int J Neuropsychopharmacol 6 325-37... 

Montel H, Starke K, Taube HD (1975) Morphine tolerance and dependence in noradrenaline neurons of the rat cerebral cortex. Naunyn-Schmiedeberg s Arch Pharmacol 258 415-26 Potkin SG, Saha AR, Kujawa MJ, Carson WH, Ali M, Stock E, Strinfellow J, Ingenito G, Marder SR (2003) Aripiprazole, an antipsychotic with a novel mechanism of action and risperidone vs. placebo in patients with schizophrenia and psychoaffective disorder. Arch Gen Psychiat 60 681-90... 

Bristol-Myers Squibb in partnership with Otsuka has recently marketed aripiprazole for the treatment of schizophrenia. The synthesis (Scheme 20) begins with acylation of 3-methoxyaniline followed by Friedel-Crafts ring closure to give quinolinone 67. Hydrogenation provides dihydroquinolinone 68, which is treated with 1,4-dibromobutane in the presence of K2CO3 to afford 69. Compound 69 was treated with Nal and then alkylated with 2,3-dichlorophenylpiperazine to give aripiprazole (5). 

In a 4-week, double-blind, randomized placebo-con-trolled study in 36 US centers 414 patients with schizophrenia or schizoaffective disorder were randomized to aripiprazole (15-30 mg/day) or haloperidol (10 mg/day) (5). Haloperidol and both doses of aripiprazole produced statistically significant improvements from baseline compared with placebo. Unlike haloperidol, aripiprazole was... 

A 34-year-old African-American woman with schizophrenia had nausea, vomiting, and malaise for 3-4 days shortly after starting to take aripiprazole therapy. She had hyperglycaemia and a metabolic acidosis, which responded rapidly to standard treatment and did not recur when aripiprazole was withdrawn. 

Medical News. FDA approves oral solution formulation of Ability (aripiprazole) for schizophrenia, http //www.medi-calnewstoday.com/articles/18670.php. 

Second-generation antipsychotics (SGAs) (also known as atypical antipsy-chotics), except clozapine, are the agents of first choice in treatment of schizophrenia. Growing, but stiU controversial, evidence supports that the SGAs (e.g., clozapine, olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole) have superior efficacy for treatment of negative symptoms, cognition, and mood. 

Marder SR, McQuade RD, Stock E, Kaplita S, Marcus R, Safferman AZ, Saha A, Ali M, Iwamoto T. Aripiprazole in the treatment of schizophrenia safety and tolerability in shortterm, placebo-controlled trials. Schizophr Res 2003 61(2-3) 123-36. 

Aripiprazole is used for the treatment of schizophrenia. The key intermediate, phenylpiperazine 56, was prepared by conventional methodology via a ring closure reaction from 2,3-dichlorophenol in six steps with an overall yield of 9%. Alternatively, phenyl-piperazine 56 was prepared via a Pd-catalyzed amination of benzyl protected 4-bromo-2,3-dichlorophenol 54 with piperazine. The coupling reactions proceeded regio-selectively to provide excellent yield of phenyl piperazine [136-140]. 

Aripiprazole, a quinoUnone derivative, is a partial agonist at dopamine D2 and serotonin 5-HTlA receptors, and antagonist at serotonin 5-HT2A receptor. Aripiprazole is indicated in the treatment of schizophrenia and treatment of acute manic and mixed episodes associated with bipolar disorder. 

---