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Identification
NameAlprenolol
Accession NumberDB00866  (APRD00736)
TypeSmall Molecule
GroupsApproved, Withdrawn
Description

One of the adrenergic beta-antagonists used as an antihypertensive, anti-anginal, and anti-arrhythmic agent. Alprenolol is no longer marketed by AstraZeneca, but may still be available in generic varieties.

Structure
Thumb
Synonyms
(RS)-1-(2-allylphenoxy)-3-(isopropylamino)propan-2-ol
1-(2-Allylphenoxy)-3-isopropylamino-2-propanol
1-(O-Allylphenoxy)-3-(isopropylamino)-2-propanol
Alfeprol
Alprenolol
Alprénolol
Alprenolol
Alprenololum
Aprenololo
External Identifiers
  • H 56/28
  • H 561/28
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
ApllobalAstraZeneca
AptinAstraZeneca
AptineNot Available
Aptol DurilesNot Available
AtenenolTsuruhara Seiyaku
ElpShyh Dar
GubernalNot Available
RegletinNot Available
SkajilolKotobuki Seiyaku
YobirNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Alprenolol hydrochloride
ThumbNot applicableDBSALT000932
Categories
UNII877K5MQ27W
CAS number13655-52-2
WeightAverage: 249.3486
Monoisotopic: 249.172878985
Chemical FormulaC15H23NO2
InChI KeyInChIKey=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
IUPAC Name
1-[2-(prop-2-en-1-yl)phenoxy]-3-[(propan-2-yl)amino]propan-2-ol
SMILES
CC(C)NCC(O)COC1=CC=CC=C1CC=C
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylpropenes. These are compounds containing a phenylpropene moiety, which consists of a propene substituent bound to a phenyl group.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenylpropenes
Direct ParentPhenylpropenes
Alternative Parents
Substituents
  • Phenylpropene
  • Phenol ether
  • Alkyl aryl ether
  • Secondary alcohol
  • 1,2-aminoalcohol
  • Secondary amine
  • Ether
  • Secondary aliphatic amine
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Alcohol
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of hypertension, angina, and arrhythmia
PharmacodynamicsAlprenolol 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 actionAlprenolol 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein binding80-90%
Metabolism

Hepatic. One of the active metabolites, 4-OH-alprenolol, is an active beta-blocker.

SubstrateEnzymesProduct
Alprenolol
Not Available
4-hydroxy-alprenololDetails
Route of eliminationNot Available
Half life2-3 hours
ClearanceNot Available
ToxicityLD50=597.0 mg/kg (Orally in rats)
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Alprenolol Action PathwayDrug actionSMP00297
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9831
Blood Brain Barrier-0.9394
Caco-2 permeable+0.8866
P-glycoprotein substrateSubstrate0.6064
P-glycoprotein inhibitor IInhibitor0.5066
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterNon-inhibitor0.8305
CYP450 2C9 substrateNon-substrate0.824
CYP450 2D6 substrateSubstrate0.882
CYP450 3A4 substrateNon-substrate0.7469
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8839
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8933
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.9106
BiodegradationNot ready biodegradable0.9646
Rat acute toxicity2.5069 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8664
hERG inhibition (predictor II)Non-inhibitor0.6946
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US3466376 No1966-06-171986-06-17Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point107-109 °CPhysProp
water solubility547 mg/LNot Available
logP3.10HANSCH,C ET AL. (1995)
Caco2 permeability-4.62ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.188 mg/mLALOGPS
logP2.59ALOGPS
logP2.69ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)14.09ChemAxon
pKa (Strongest Basic)9.67ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area41.49 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity74.66 m3·mol-1ChemAxon
Polarizability29.38 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (3.94 KB)
SpectraNot Available
References
Synthesis Reference

http://www.google.com.mx/patents/US3466376

General References
  1. Hold KM, de Boer D, Bos KL, van Ooijen RD, Zuidema J, Maes RA: Enantioselective quantitation of (R)- and (S)-alprenolol by gas chromatography-mass spectrometry in human saliva an plasma. J Chromatogr Sci. 1996 Jan;34(1):13-9. [PubMed:8586675 ]
  2. Himori N, Ishimori T, Izumi A, Hiramatsu Y: Effects of beta-adrenoceptor blocking agents, pindolol, alprenolol and practolol on blood pressure and heart rate in conscious renal hypertensive dogs. Arch Int Pharmacodyn Ther. 1977 Jan;225(1):152-65. [PubMed:15525 ]
External Links
ATC CodesC07AA01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (28.7 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Receptor signaling protein activity
Specific Function:
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. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling.
Gene Name:
ADRB1
Uniprot ID:
P08588
Molecular Weight:
51322.1 Da
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:7678677 ]
  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:7606348 ]
  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:10433496 ]
  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:12522078 ]
  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:2828119 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Protein homodimerization activity
Specific Function:
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.
Gene Name:
ADRB2
Uniprot ID:
P07550
Molecular Weight:
46458.32 Da
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:2439825 ]
  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:2859531 ]
  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:2871880 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G pro...
Gene Name:
HTR1A
Uniprot ID:
P08908
Molecular Weight:
46106.335 Da
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:1323650 ]
  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:8392199 ]
  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:9145928 ]
  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:9806333 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
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.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
References
  1. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Comments
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Drug created on June 13, 2005 07:24 / Updated on December 03, 2014 20:12