Asenapine

Các tên gọi khác (1) :

Saphris

Thuốc Gốc

Small Molecule

CAS: 65576-45-6

ATC: N05AH05

CTHH: C₂₁H₂₀ClNO₅

PTK: 401.84

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.

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₂₁H₂₀ClNO₅

Phân tử khối

401.84

Monoisotopic mass

401.103000462

InChI

InChI=1S/C17H16ClNO.C4H4O4/c1-19-9-14-12-4-2-3-5-16(12)20-17-7-6-11(18)8-13(17)15(14)10-19;5-3(6)1-2-4(7)8/h2-8,14-15H,9-10H2,1H3;1-2H,(H,5,6)(H,7,8)/b;2-1-

InChI Key

InChIKey=GMDCDXMAFMEDAG-BTJKTKAUSA-N

IUPAC Name

(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

Traditional IUPAC Name

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; maleic acid

SMILES

OC(=O)\C=C/C(O)=O.CN1CC2C(C1)C1=C(OC3=CC=CC=C23)C=CC(Cl)=C1

logP

3.72

pKa (Strongest Basic)

7.29

PSA

12.47 Å²

Refractivity

81.65 m³·mol^-1

Polarizability

30.9 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

Rule of Five

true

Ghose Filter

true

Dược Lực Học : 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.

Cơ Chế Tác Dụng : 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. 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.

Dược Động Học :

▧ 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)

Chỉ Định : Used for treatment in psychosis, schizophrenia and schizoaffective disorders, manic disorders, and bipolar disorders as monotherapy or in combination.

Tương Tác Thuốc :

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).

Liều Lượng & Cách Dùng : Tablet - Sublingual - 5 mg, 10 mg

Dữ Kiện Thương Mại

Nhà Sản Xuất

Công ty : Organon Sub Merck

Sản phẩm biệt dược : Saphris
Công ty : Lundbeck

Sản phẩm biệt dược : Sycrest

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB06216

PubChem Compound

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=11954293

PubChem Substance

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=17397151

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D02995

ChemSpider

http://www.chemspider.com/Chemical-Structure.10128588.html

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0052-2139-03

Wikipedia

http://en.wikipedia.org/wiki/Asenapine

RxList

http://www.rxlist.com/saphris-drug.htm

Drugs.com

http://www.drugs.com/mtm/asenapine.html

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