Asenapine

Asenapine (INN, trade names Saphris, Sycrest) is a new atypical antipsychotic developed for the treatment of schizophrenia and acute mania associated with bipolar disorder by Schering-Plough after its November 19, 2007 merger with Organon International. Development of the drug, through Phase III trials, began while Organon was still a part of Akzo Nobel. Preliminary data indicate that it has minimal anticholinergic and cardiovascular side effects, as well as minimal weight gain. Over 3000 patients have participated in clinical trials of asenapine, and the FDA accepted the manufacturer's NDA on November 26, 2007 for standard review.

Some American psychiatrists have begun to prescribe the drug to combat veterans with severe PTSD nightmares as an "off-label" use, although this use is not yet allowed by the United States Department of Veterans Administration. (Search "Formulary" at www.va.gov)

Pharmacology
Asenapine shows high affinity (pKi) for numerous receptors, including the serotonin 5-HT1A (8.6), 5-HT1B (8.4), 5-HT2A (10.2), 5-HT2B (9.8), 5-HT2C (10.5), 5-HT5A (8.8), 5-HT6 (9.5), and 5-HT7 (9.9) receptors, the adrenergic α1 (8.9), α2A (8.9), α2B (9.5), and α2C (8.9) receptors, the dopamine D1 (8.9), D2 (8.9), D3 (9.4), and D4 (9.0) receptors, and the histamine H1 (9.0) and H2 (8.2) receptors. It has much lower affinity (pKi < 5) for the muscarinic acetylcholine receptors. Asenapine behaves as an a partial agonist at the 5-HT1A and D1 receptors. At all other targets Asenapine is an antagonist. As of November 2010 Asenapine is also in clinical trials at UC Irvine to treat stuttering.

Indications and usage
Asenapine has been approved by the FDA for the acute treatment of adults with schizophrenia and acute treatment of manic or mixed episodes associated with bipolar I disorder with or without psychotic features in adults.

Side effects
Common side effects: (incidence at least 5% or greater and at least twice that for placebo or greater than 10% regardless of placebo rate) Severe akathisia, oral hypothesia, somnolence, dizziness, extrapyramidal symptoms other than akathisia, weight gain, insomnia, extreme sedation, headache.

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

The FDA has warned healthcare professionals and patients that serious allergic reactions have been reported with the use of Saphris.Healthcare professionals and patients are encouraged to report adverse events or side effects to the FDA's MedWatch Safety Information and Adverse Event Reporting Program.

Synthesis


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