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Identification
Name Alprenolol
Accession Number DB00866 (APRD00736)
Type small molecule
Groups approved
Description

One of the adrenergic beta-antagonists used as an antihypertensive, anti-anginal, and anti-arrhythmic agent. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Alfeprol [Russian]
  • Alpheprol
  • Alprenololum [INN-Latin]
Brand names
  • Apllobal
  • Aptine
  • Aptol Duriles
  • Gubernal
  • Regletin
  • Yobir
Brand name mixtures Not Available
Categories
  • Antihypertensive Agents
  • Adrenergic beta-Antagonists
  • Sympatholytics
  • Antiarrhythmic Agents
  • Anti-Arrhythmia Agents
CAS number 13655-52-2
Weight Average: 249.3486
Monoisotopic: 249.172878985
Chemical Formula C15H23NO2
InChI Key InChIKey=PAZJSJFMUHDSTF-UHFFFAOYSA-N
InChI
InChI=1S/C15H23NO2/c1-4-7-13-8-5-6-9-15(13)18-11-14(17)10-16-12(2)3/h4-6,8-9,12,14,16-17H,1,7,10-11H2,2-3H3
Plain Text
IUPAC Name
{2-hydroxy-3-[2-(prop-2-en-1-yl)phenoxy]propyl}(propan-2-yl)amine
SMILES
CC(C)NCC(O)COC1=C(CC=C)C=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenols and Derivatives
  • Ethers
  • Anisoles
  • Phenyl Esters
Substructures
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Amino Alcohols
  • Aromatic compounds
  • Anisoles
  • Alcohols and Polyols
  • Phenyl Esters
Pharmacology
Indication For the treatment of hypertension, angina, and arrhythmia
Pharmacodynamics Alprenolol is a non-selective beta-blocker used in the treatment of hypertension, edema, ventricular tachycardias, and atrial fibrillation. Alprenolol impairs AV node conduction and decreases sinus rate and may also increase plasma triglycerides and decrease HDL-cholesterol levels. Alprenolol is nonpolar and hydrophobic, with low to moderate lipid solubility. Alprenolol has little to no intrinsic sympathomimetic activity and, unlike some other beta-adrenergic blocking agents, alprenolol has little direct myocardial depressant activity and does not have an anesthetic-like membrane-stabilizing action.
Mechanism of action Alprenolol non-selectively blocks beta-1 adrenergic receptors mainly in the heart, inhibiting the effects of epinephrine and norepinephrine resulting in a decrease in heart rate and blood pressure. Also, with a more minor effect, by binding beta-2 receptors in the juxtaglomerular apparatus, alprenolol inhibits the production of renin, thereby inhibiting angiotensin II and aldosterone production and therefore inhibits the vasoconstriction and water retention due to angiotensin II and aldosterone, respectively.
Absorption Not Available
Volume of distribution Not Available
Protein binding 80-90%
Metabolism

Hepatic. One of the active metabolites, 4-OH-alprenolol, is an active beta-blocker.
Route of elimination Not Available
Half life 2-3 hours
Clearance Not Available
Toxicity LD50=597.0 mg/kg (Orally in rats)
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00297 Alprenolol Pathway SMP00297
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms Not Available
Prices Not Available
Patents Not Available
Properties
State solid
Melting point 107-109 oC
Experimental Properties
Property Value Source
water solubility 547 mg/L PhysProp
logP 2.8 PhysProp
Caco2 permeability -4.62 [ADME Research, USCD] BiGG
Predicted Properties
Property Value Source
water solubility 1.88e-01 g/l ALOGPS
logP 2.59 ALOGPS
logP 2.69 ChemAxon Molconvert
logS -3.12 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 41.49 ChemAxon Molconvert
rotatable bond count 8 ChemAxon Molconvert
refractivity 74.66 ChemAxon Molconvert
polarizability 29.38 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
PubChem Compound 2119 Link_out
PubChem Substance 46506033 Link_out
ChemSpider 2035 Link_out
BindingDB 25764 Link_out
ChEBI 51211 Link_out
ChEMBL 51211 Link_out
Therapeutic Targets Database DAP000941 Link_out
Drug Product Database 0 Link_out
ATC Codes
  • C07AA01
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Food Interactions Not Available
Targets

1. Beta-1 adrenergic receptor

Pharmacological action: yes
Actions: antagonist

Beta-adrenergic receptors mediate the catecholamine- induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity

Organism class: human
UniProt ID: P08588 Link_out
Gene: ADRB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Surman AJ, Doggrell SA: Alprenolol and bromoacetylalprenololmenthane are competitive slowly reversible antagonists at the beta 1-adrenoceptors of rat left atria. J Cardiovasc Pharmacol. 1993 Jan;21(1):35-9. Pubmed
  2. De Ponti F, Cosentino M, Costa A, Girani M, Gibelli G, D’Angelo L, Frigo G, Crema A: Inhibitory effects of SR 58611A on canine colonic motility: evidence for a role of beta 3-adrenoceptors. Br J Pharmacol. 1995 Apr;114(7):1447-53. Pubmed
  3. Varma DR, Shen H, Deng XF, Peri KG, Chemtob S, Mulay S: Inverse agonist activities of beta-adrenoceptor antagonists in rat myocardium. Br J Pharmacol. 1999 Jun;127(4):895-902. Pubmed
  4. Brahmadevara N, Shaw AM, MacDonald A: Evidence against beta 3-adrenoceptors or low affinity state of beta 1-adrenoceptors mediating relaxation in rat isolated aorta. Br J Pharmacol. 2003 Jan;138(1):99-106. Pubmed
  5. Im MJ, Holzhofer A, Bottinger H, Pfeuffer T, Helmreich EJ: Interactions of pure beta gamma-subunits of G-proteins with purified beta 1-adrenoceptor. FEBS Lett. 1988 Jan 25;227(2):225-9. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Beta-2 adrenergic receptor

Pharmacological action: yes
Actions: antagonist

Beta-adrenergic receptors mediate the catecholamine- induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine

Organism class: human
UniProt ID: P07550 Link_out
Gene: ADRB2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Brodde OE, Wang XL, O’Hara N, Daul A, Schiess W: Effect of propranolol, alprenolol, pindolol, and bopindolol on beta 2-adrenoceptor density in human lymphocytes. J Cardiovasc Pharmacol. 1986;8 Suppl 6:S70-3. Pubmed
  2. Brodde OE, Daul A, Stuka N, O’Hara N, Borchard U: Effects of beta-adrenoceptor antagonist administration on beta 2-adrenoceptor density in human lymphocytes. The role of the “intrinsic sympathomimetic activity”. Naunyn Schmiedebergs Arch Pharmacol. 1985 Feb;328(4):417-22. Pubmed
  3. Abrahamsson T: The beta 1- and beta 2-adrenoceptor stimulatory effects of alprenolol, oxprenolol and pindolol: a study in the isolated right atrium and uterus of the rat. Br J Pharmacol. 1986 Apr;87(4):657-64. Pubmed

3. 5-hydroxytryptamine 1A receptor

Pharmacological action: yes
Actions: antagonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity

Organism class: human
UniProt ID: P08908 Link_out
Gene: HTR1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Millan MJ, Rivet JM, Canton H, Lejeune F, Bervoets K, Brocco M, Gobert A, Lefebvre de Ladonchamps B, Le Marouille-Girardon S, Verriele L, et al.: S 14671: a naphtylpiperazine 5-hydroxytryptamine1A agonist of exceptional potency and high efficacy possessing antagonist activity at 5-hydroxytryptamine1C/2 receptors. J Pharmacol Exp Ther. 1992 Aug;262(2):451-63. Pubmed
  2. Darmani NA: Role of the inhibitory adrenergic alpha 2 and serotonergic 5-HT1A components of cocaine’s actions on the DOI-induced head-twitch response in 5-HT2-receptor supersensitive mice. Pharmacol Biochem Behav. 1993 Jun;45(2):269-74. Pubmed
  3. Kuipers W, Link R, Standaar PJ, Stoit AR, Van Wijngaarden I, Leurs R, Ijzerman AP: Study of the interaction between aryloxypropanolamines and Asn386 in helix VII of the human 5-hydroxytryptamine1A receptor. Mol Pharmacol. 1997 May;51(5):889-96. Pubmed
  4. Misane I, Johansson C, Ogren SO: Analysis of the 5-HT1A receptor involvement in passive avoidance in the rat. Br J Pharmacol. 1998 Oct;125(3):499-509. Pubmed
Enzymes

1. Cytochrome P450 2D6

Actions: substrate

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:07

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