药品详细

Asenapine(阿塞那平)

基本信息
剂型规格
适应症
药理
临床
理化性质
相互作用
文档
专利
Pathway
文献
序列

化学结构式图

中文名

阿塞那平

英文名

Asenapine

分子式

C₂₁H₂₀ClNO₅

化学名

(2Z)-but-2-enedioic acid; 9-chloro-4-methyl-13-oxa-4-azatetracyclo[12.4.0.0^{2,6}.0^{7,12}]octadeca-1(14),7(12),8,10,15,17-hexaene

分子量

Average: 401.84
Monoisotopic: 401.103000462

CAS号

65576-45-6

ATC分类

N05A 未知

药物类型

small molecule

阶段

approved

商品名

同义名

基本介绍

Developed by Schering-Plough after its merger with Organon International, asenapine is a sublingually administered, atypical antipsychotic for treatment of schizophrenia and acute mania associated with bipolar disorder. Asenapine also belongs to the dibenzo-oxepino pyrrole class. It is also for severe post-traumatic stress disorder nightmares in soldiers as an off-label use. FDA approved on August 13, 2009.

生产厂家

Organon usa inc

封装厂家

参考

Synthesis Reference

Not Available

General Reference

Huang M, Li Z, Dai J, Shahid M, Wong EH, Meltzer HY: Asenapine Increases Dopamine, Norepinephrine, and Acetylcholine Efflux in the Rat Medial Prefrontal Cortex and Hippocampus. Neuropsychopharmacology. 2008 Apr 16;. Pubmed
Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologicagent with a unique human receptor signature. J Psychopharmacol. 2008 Feb 28;. Pubmed
Franberg O, Wiker C, Marcus MM, Konradsson A, Jardemark K, Schilstrom B, Shahid M, Wong EH, Svensson TH: Asenapine, a novel psychopharmacologic agent: preclinical evidence for clinical effects in schizophrenia. Psychopharmacology (Berl). 2008 Feb;196(3):417-29. Epub 2007 Oct 17. Pubmed
Fagiolini A, Forgione RN, Morana B, Maccari M, Goracci A, Bossini L, Pellegrini F, Cuomo A, Casamassima F: Asenapine for the treatment of manic and mixed episodes associated with bipolar I disorder: from clinical research to clinical practice. Expert Opin Pharmacother. 2013 Mar;14(4):489-504. doi: 10.1517/14656566.2013.765859. Epub 2013 Jan 29. Pubmed

剂型

规格

化合物类型

Type	small molecule

Classes

Not Available

Substructures

Not Available

适应症

药理

Indication	Used for treatment in psychosis, schizophrenia and schizoaffective disorders, manic disorders, and bipolar disorders as monotherapy or in combination.
Pharmacodynamics	Asenapine is a serotonin, dopamine, noradrenaline, and histamine antagonist in which asenapine possess more potent activity with serotonin receptors than dopamine. Sedation in patients is associated with asenapine's antagonist activity at histamine receptors. Its lower incidence of extrapyramidal effects are associated with the upregulation of D1 receptors. This upregulation occurs due to asenapine's dose-dependent effects on glutamate transmission in the brain. It does not have any significant activity with muscarinic, cholinergic receptors therefore symptoms associated with anticholinergic drug activity like dry mouth or constipation are not expected to be observed. Asenapine has a higher affinity for all aforementioned receptors compared to first-generation and second-generation antipsychotics except for 5-HT1A and 5-HT1B receptors.
Mechanism of action	Asenapine is an atypical antipsychotic multireceptor neuroleptic drug which shows strong 5HT2A (serotonin) and D2 (dopamine) receptor antagonism, which has been shown to enhance dopamine (DA) and acetylcholine (Ach) efflux in rat brains. Asenapine may improve cognitive function and negative symptoms in patients with schizophrenia.
Absorption	Cmax, single 5 mg dose = 4 ng/mL (within 1 hour); Bioavailability, sublingual administration = 35%; Bioavailability, oral administration (swallowed) = <2%; Time to steady state, 5 mg = 3 days; Peak plasma concentration occurs within 0.5 to 1.5 hours. Doubling dose of asenapine results in 1.7-fold increase in maximum concentration and exposure. Drinking water within 2-5 minutes post administration of asenapine results in a decrease in exposure.
Volume of distribution	20-25 L/kg
Protein binding	95% protein bound
Metabolism	Asenapine is oxidized via CYP1A2 and undergoes direct glucuronidation via UGT1A4. Oxidation via CYP1A2 is asenapine's primary mode of metabolism.
Route of elimination	Urine (50%) and feces (50%)
Half life	24 hours (range of 13.4 - 39.2 hours)
Clearance	Not Available
Toxicity	Not Available
Affected organisms	Humans and other mammals
Pathways	Not Available

理化性质

Properties

State

solid

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
logP	3.72	ChemAxon
pKa (strongest basic)	7.29	ChemAxon
physiological charge	1	ChemAxon
hydrogen acceptor count	1	ChemAxon
hydrogen donor count	0	ChemAxon
polar surface area	12.47	ChemAxon
rotatable bond count	2	ChemAxon
refractivity	81.65	ChemAxon
polarizability	30.9	ChemAxon

药物相互作用

Drug	Interaction
Artemether	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Carbamazepine	Carbamazepine is a CYP1A2 inducer that decreases asenapine's exposure by 20%.
Fluvoxamine	Fluvoxamine is a CYP1A2 inhibitor that increases exposure of asenapine by 30%.
Indacaterol	Concomitant therapy with monoamine oxidase inhibitors, tricyclic antidepressants, or other drugs that prolong the QTc interval should be monitored closely. These drugs may potentiate the effect of adrenergic agonist on the cardiovascular system.
Lumefantrine	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Ondansetron	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Paroxetine	Paroxetine is a substrate of CYP2D6 and concomitant therapy with asenapine (CYP2D6 inhibitor) increases concentrations of paroxetine 2-fold. May require dosing adjustments.
Phenobarbital	Phenobarbital is a CYP1A2 inducer and may increase metabolism of asenapine.
Phenytoin	Phenytoin is a CYP1A2 inducer and may increase metabolism of asenapine.
Primidone	Primidone is a CYP1A2 inducer and may increase metabolism of asenapine.
Saquinavir	Increased incidence of adverse effects due to pharmacodynamic synergism. Concomitant therapy should be avoided.
Sildenafil	Increased incidence of adverse effects (hypotension) due to pharmacodynamic synergism. Concomitant therapy should be avoided.
Thioridazine	Thioridazine is a CYP2D6 substrate in which concomitant therapy with asenapine will increase serum levels of thioridazine. Consider alternative therapy.
Toremifene	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Valproic Acid	Valproate completely inhibits the glucuronidation of asenapine but does not effect its exposure. Dose adjustment is not necessary with concomitant therapy.
Voriconazole	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Vorinostat	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Yohimbine	Increased incidence of adverse effects due to pharmacodynamic synergism. Concomitant therapy should be avoided.
Ziprasidone	Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Zuclopenthixol	Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

食物相互作用

Avoid water and food for at least 10 minutes post administration of asenapine

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