Chemical Properties and Mechanism of Action for Asenapine -- (Saphris)

Asenapine (Saphris) 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 merge with Organon International. Development of the drug, through Phase III trials, began while Organon was still a part of Akzo Nobel.^[1] 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.^[2]

Pharmacology

Asenapine shows high affinity (pKi) for numerous receptors, including the serotonin 5-HT_1A (8.6), 5-HT_1B (8.4), 5-HT_2A (10.2), 5-HT_2B (9.8), 5-HT_2C (10.5), 5-HT_5A (8.8), 5-HT₆ (9.5), and 5-HT₇ (9.9) receptors, the adrenergic α₁ (8.9), α_2A (8.9), α_2B (9.5), and α_2C (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.^[3] It has much lower affinity (pKi < 5) for the muscarinic acetylcholine receptors. Asenapine behaves as an antagonist at all receptors.^[3]

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.^[4]

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) Akathisia, oral hypothesia, somnolence, dizziness, extrapyramidal symptoms other than akathisia, weight gain, insomnia, 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.

References

"Bipolar Disorder". Clinical Trials Update (Genetic Engineering & Biotechnology News): pp. 52,55. 2007-06-15.
^ Schering-Plough "Schering-Plough Announces Asenapine NDA Accepted for Filing by the U.S. FDA". Press release. http://www.schering-plough.com/news/news_article.aspx?reqid=1080771. Retrieved 2008-12-29.
^ ^a ^b ^c Shahid M, Walker GB, Zorn SH, Wong EH. (2009). "Asenapine: a novel psychopharmacologic agent with a unique human receptor signature.". J Psychopharmacol. 23 (1): 65-73.
^ ^a ^b "Saphris (asenapine) prescribing information" (PDF). Schering Corporation. 2009-08-01. http://www.spfiles.com/pisaphrisv1.pdf. Retrieved 2009-09-05.