Identification

Name
Alprenolol
Accession Number
DB00866  (APRD00736)
Type
Small Molecule
Groups
Experimental, Withdrawn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
  • Alprenololum
  • Aprenololo
External IDs
H 56/28 / H 561/28
Product Ingredients
IngredientUNIICASInChI Key
Alprenolol hydrochloride2502C2OIRK13707-88-5RRCPAXJDDNWJBI-UHFFFAOYSA-N
International/Other Brands
Apllobal (AstraZeneca) / Aptin (AstraZeneca) / Aptine / Aptol Duriles / Atenenol (Tsuruhara Seiyaku) / Elp (Shyh Dar) / Gubernal / Regletin / Skajilol (Kotobuki Seiyaku) / Yobir
Categories
UNII
877K5MQ27W
CAS number
13655-52-2
Weight
Average: 249.3486
Monoisotopic: 249.172878985
Chemical Formula
C15H23NO2
InChI Key
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

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.

TargetActionsOrganism
ABeta-1 adrenergic receptor
antagonist
Human
ABeta-2 adrenergic receptor
antagonist
Human
A5-hydroxytryptamine receptor 1A
antagonist
Human
UBeta-3 adrenergic receptor
antagonist
Human
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
PathwayCategory
Alprenolol Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of adverse effects can be increased when Alprenolol is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Alprenolol is combined with (S)-Warfarin.
1,10-Phenanthroline1,10-Phenanthroline may increase the bradycardic activities of Alprenolol.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Alprenolol is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe risk or severity of adverse effects can be increased when Alprenolol is combined with 3-isobutyl-1-methyl-7H-xanthine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Alprenolol is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Alprenolol is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe risk or severity of adverse effects can be increased when Alprenolol is combined with 4-hydroxycoumarin.
4-MethoxyamphetamineThe therapeutic efficacy of 4-Methoxyamphetamine can be decreased when used in combination with Alprenolol.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Alprenolol is combined with 5-methoxy-N,N-dimethyltryptamine.
Food Interactions
Not 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
Human Metabolome Database
HMDB0015004
KEGG Drug
D07156
PubChem Compound
2119
PubChem Substance
46506033
ChemSpider
2035
BindingDB
25764
ChEBI
51211
ChEMBL
CHEMBL266195
Therapeutic Targets Database
DAP000941
PharmGKB
PA164750541
Drugs.com
Drugs.com Drug Page
Wikipedia
Alprenolol
ATC Codes
C07AA01 — Alprenolol
MSDS
Download (28.7 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US3466376No1966-06-171986-06-17Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)107-109 °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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Download (3.94 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenol ethers
Sub Class
Not Available
Direct Parent
Phenol ethers
Alternative Parents
Phenoxy compounds / Alkyl aryl ethers / Secondary alcohols / 1,2-aminoalcohols / Dialkylamines / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Phenoxy compound / Phenol ether / Alkyl aryl ether / Monocyclic benzene moiety / 1,2-aminoalcohol / Secondary alcohol / Secondary aliphatic amine / Secondary amine / Ether / Organic nitrogen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
secondary alcohol, secondary amino compound (CHEBI:51211)

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 e...
Gene Name
ADRB1
Uniprot ID
P08588
Uniprot Name
Beta-1 adrenergic receptor
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 ...
Gene Name
ADRB2
Uniprot ID
P07550
Uniprot Name
Beta-2 adrenergic receptor
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...
Gene Name
HTR1A
Uniprot ID
P08908
Uniprot Name
5-hydroxytryptamine receptor 1A
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Beta-3 is involved in the regulation of lipolysis and thermogenesis.
Gene Name
ADRB3
Uniprot ID
P13945
Uniprot Name
Beta-3 adrenergic receptor
Molecular Weight
43518.615 Da
References
  1. Hoffmann C, Leitz MR, Oberdorf-Maass S, Lohse MJ, Klotz KN: Comparative pharmacology of human beta-adrenergic receptor subtypes--characterization of stably transfected receptors in CHO cells. Naunyn Schmiedebergs Arch Pharmacol. 2004 Feb;369(2):151-9. Epub 2004 Jan 17. [PubMed:14730417]

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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
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]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:44