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药品详细

Penbutolol(喷布洛尔)

化学结构式图
中文名
喷布洛尔
英文名
Penbutolol
分子式
C18H29NO2
化学名
tert-butyl[(2S)-3-(2-cyclopentylphenoxy)-2-hydroxypropyl]amine
分子量
Average: 291.4284
Monoisotopic: 291.219829177
CAS号
36507-48-9
ATC分类
C07A 未知
药物类型
small molecule
阶段
approved, experimental
商品名
同义名
基本介绍

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.

生产厂家
  • Schwarz pharma inc
封装厂家
  • Schwarz Pharma Inc.
参考
Synthesis Reference Not Available
General Reference
  1. Maurer HH, Tenberken O, Kratzsch C, Weber AA, Peters FT: Screening for library-assisted identification and fully validated quantification of 22 beta-blockers in blood plasma by liquid chromatography-mass spectrometry with atmospheric pressure chemical ionization. J Chromatogr A. 2004 Nov 26;1058(1-2):169-81. Pubmed
  2. Aguirre C, Rodriguez-Sasiain JM, Calvo R: Decrease in penbutolol protein binding as a consequence of treatment with some alkylating agents. Cancer Chemother Pharmacol. 1994;34(1):86-8. Pubmed
  3. Hjorth S: (-)-Penbutolol as a blocker of central 5-HT1A receptor-mediated responses. Eur J Pharmacol. 1992 Nov 3;222(1):121-7. Pubmed
  4. Pepe S, Scalici G, D’Angelo A, Curiale B, Corrao S, Agnello C: [Validity of the use of penbutolol in essential arterial hypertension]. Minerva Med. 1990 Jun;81(6):471-3. Pubmed
  5. Frishman WH, Covey S: Penbutolol and carteolol: two new beta-adrenergic blockers with partial agonism. J Clin Pharmacol. 1990 May;30(5):412-21. Pubmed
  6. Martinez Jorda R, Aguirre C, Calvo R, Rodriguez-Sasiain JM, Erill S: Decrease in penbutolol central response as a cause of changes in its serum protein binding. J Pharm Pharmacol. 1990 Mar;42(3):164-6. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Phenols and Derivatives
  • Ethers
  • Anisoles
  • Phenyl Esters
Substructures
  • Hydroxy Compounds
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Amino Alcohols
  • Aromatic compounds
  • Anisoles
  • Alcohols and Polyols
  • Phenyl Esters
适应症
药理
Indication 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.
Pharmacodynamics 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.
Mechanism of action 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.
Absorption >90%.
Volume of distribution Not Available
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.
Toxicity Symptoms of overdose include drowsiness, vertigo, headache, and atriventricular block.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00305 Penbutolol Pathway SMP00305
理化性质
Properties
State solid
Experimental Properties
Property Value Source
boiling point 438.2 http://www.chemnet.com/cas/fr/38363-40-5/Penbutolol.html
logP 4.15 HANSCH,C ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 2.12e-02 g/l ALOGPS
logP 3.84 ALOGPS
logP 3.55 ChemAxon
logS -4.1 ALOGPS
pKa (strongest acidic) 14.09 ChemAxon
pKa (strongest basic) 9.76 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 41.49 ChemAxon
rotatable bond count 7 ChemAxon
refractivity 86.6 ChemAxon
polarizability 34.58 ChemAxon
药物相互作用
Drug Interaction
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.
食物相互作用
Not Available

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