Penbutolol

Các tên gọi khác (8 ) :

(2S)-1-(tert-butylamino)-3-(2-cyclopentylphenoxy)propan-2-ol
1-(tert-Butylamino)-3-(o-cyclopentylphenoxy)propan-2-ol
2-Propanol, 1-(2-cyclopentylphenoxy)-3-((1,1-dimethylethyl)amino)-, (S)-
HOE 893
HOE 893D
Levatol
Penbutolol
Penbutololum

antihypertensive agents, adrenergic beta antagonists

Thuốc Gốc

Small Molecule

CAS: 36507-48-9

ATC: C07AA23

ĐG : Schwarz Pharma Inc.

CTHH: C₁₈H₂₉NO₂

PTK: 291.4284

Penbutolol is a drug in the beta-blocker class used to treat hypertension. Penbutolol binds both beta-1 and beta-2 adrenergic receptors, rendering it a non-selective beta-blocker. Penbutolol can act as a partial agonist at beta adrenergic receptors, since it is a sympathomimetric drug. Penbutolol also demonstrates high binding affinity to the 5-hydroxytryptamine receptor 1A with antagonistic effects. This binding characteristic of penbutolol is being investigated for its implications in Antidepressant Therapy. Penbutolol is contraindicated in patients with cardiogenic shock, sinus bradycardia, second and third degree atrioventricular conduction block, bronchial asthma, and those with known hypersensitivity.

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₁₈H₂₉NO₂

Phân tử khối

291.4284

Monoisotopic mass

291.219829177

InChI

InChI=1S/C18H29NO2/c1-18(2,3)19-12-15(20)13-21-17-11-7-6-10-16(17)14-8-4-5-9-14/h6-7,10-11,14-15,19-20H,4-5,8-9,12-13H2,1-3H3/t15-/m0/s1

InChI Key

InChIKey=KQXKVJAGOJTNJS-HNNXBMFYSA-N

IUPAC Name

tert-butyl[(2S)-3-(2-cyclopentylphenoxy)-2-hydroxypropyl]amine

Traditional IUPAC Name

penbutolol

SMILES

CC(C)(C)NC[C@H](O)COC1=CC=CC=C1C1CCCC1

Độ sôi

438.2

Độ hòa tan

2.12e-02 g/l

logP

4.15

logS

-4.1

pKa (strongest acidic)

14.09

pKa (Strongest Basic)

9.76

PSA

41.49 Å²

Refractivity

86.6 m³·mol^-1

Polarizability

34.58 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 : Penbutolol is a ß-1, ß-2 (nonselective) adrenergic receptor antagonist. Experimental studies showed a dose-dependent increase in heart rate in reserpinized (norepinephrine-depleted) rats given penbutolol intravenously at doses of 0.25 to 1.0 mg/kg, suggesting that penbutolol has some intrinsic sympathomimetic activity. In human studies, however, heart rate decreases have been similar to those seen with propranolol.

Cơ Chế Tác Dụng : Penbutolol is a drug in the beta-blocker class used to treat hypertension. Penbutolol binds both beta-1 and beta-2 adrenergic receptors, rendering it a non-selective beta-blocker. Penbutolol can act as a partial agonist at beta adrenergic receptors, since it is a sympathomimetric drug. Penbutolol also demonstrates high binding affinity to the 5-hydroxytryptamine receptor 1A with antagonistic effects. This binding characteristic of penbutolol is being investigated for its implications in Antidepressant Therapy. Penbutolol is contraindicated in patients with cardiogenic shock, sinus bradycardia, second and third degree atrioventricular conduction block, bronchial asthma, and those with known hypersensitivity. Penbutolol acts on the β1 adrenergic receptors in both the heart and the kidney. When β1 receptors are activated by catecholamines, they stimulate a coupled G protein that leads to the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). The increase in cAMP leads to activation of protein kinase A (PKA), which alters the movement of calcium ions in heart muscle and increases the heart rate. Penbutolol blocks the catecholamine activation of β1 adrenergic receptors and decreases heart rate, which lowers blood pressure.

Dược Động Học :

▧ Absorption :
>90%.
▧ Protein binding :
80-98% bound to plasma proteins. Extensively bound to Alpha-1-acid glycoprotein 1.
▧ Metabolism :
Metabolized in the liver by hydroxylation and glucuroconjugation forming a glucuronide metabolite and a semi-active 4-hydroxy metabolite.
▧ Route of Elimination :
The metabolites are excreted principally in the urine.
▧ Half Life :
Plasma= approximately 5h Conjugated= approximately 20h in healthy persons, 25h in healthy elderly persons, and 100h in patients on renal dialysis.
▧ Clearance :
Approximately 90% of the metabolites are excreted in the urine.

Độc Tính : Symptoms of overdose include drowsiness, vertigo, headache, and atriventricular block.

Chỉ Định : Penbutolol is indicated in the treatment of mild to moderate arterial hypertension. It may be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.Penbutolol is contraindicated in patients with cardiogenic shock, sinus bradycardia, second and third degree atrioventricular conduction block, bronchial asthma, and those with known hypersensitivity.

Tương Tác Thuốc :

Aminophylline Antagonism of action and increased effect of theophylline
Chlorpropamide The beta-blocker, penbutolol, may decrease symptoms of hypoglycemia.
Clonidine Increased hypertension when clonidine stopped
Digoxin Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.
Dihydroergotamine Ischemia with risk of gangrene
Disopyramide The beta-blocker, penbutolol, may increase the toxicity of disopyramide.
Epinephrine Hypertension, then bradycardia
Ergotamine Ischemia with risk of gangrene
Fenoterol Antagonism
Formoterol Antagonism
Gliclazide The beta-blocker, penbutolol, may decrease symptoms of hypoglycemia.
Glyburide The beta-blocker, penbutolol, may decrease symptoms of hypoglycemia.
Ibuprofen Risk of inhibition of renal prostaglandins
Indomethacin Risk of inhibition of renal prostaglandins
Insulin Glargine The beta-blocker, penbutolol, may decrease symptoms of hypoglycemia.
Lidocaine Penbutolol increases the volume of distribution of lidocaine in normal subjects. This could result in a requirement for higher loading doses of lidocaine.
Methyldopa Possible hypertensive crisis
Methysergide Ischemia with risk of gangrene
Orciprenaline Antagonism
Oxtriphylline Antagonism of action and increased effect of theophylline
Pipobroman Antagonism
Piroxicam Risk of inhibition of renal prostaglandins
Prazosin Risk of hypotension at the beginning of therapy
Repaglinide The beta-blocker, penbutolol, may decrease symptoms of hypoglycemia.
Terazosin Increased risk of hypotension. Initiate concomitant therapy cautiously.
Terbutaline Antagonism
Theophylline Antagonism of action and increased effect of theophylline
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.

Liều Lượng & Cách Dùng : Tablet - Oral - 20 mg, yellow, oval.

Dữ Kiện Thương Mại

Giá thị trường

Biệt dược thương mại : Levatol 20 mg tablet

Giá bán buôn : USD >2.87

Đơn vị tính : tablet

Nhà Sản Xuất

Công ty : Hoechst Ltd.

Sản phẩm biệt dược : Betapressin
Công ty : Schwarz Pharma

Sản phẩm biệt dược : Levatol
Công ty :

Sản phẩm biệt dược : Levatolol
Công ty : Sanofi-Aventis

Sản phẩm biệt dược : Lobeta

Đóng gói

Công ty : Schwarz Pharma Inc.

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB01359

PubChem Compound

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=37464

PubChem Substance

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46504929

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D00602

ChemSpider

http://www.chemspider.com/Chemical-Structure.34369.html

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0091-4500-15

PharmGKB

http://www.pharmgkb.org/drug/PA164749474

Wikipedia

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

Drugs.com

http://www.drugs.com/cdi/penbutolol.html

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