Banner
Identification
Name Propranolol
Accession Number DB00571 (APRD00194)
Type small molecule
Groups approved
Description

A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Dl-Propranolol Hydrochloride
  • Propanalol
  • Propanolol
  • Propranalol
  • propranolol
  • Propranolol Hcl
  • Propranolol Hydrochloride
  • R,S-Propranolol Hydrochloride
Brand names
  • Angilol
  • Apsolol
  • Avlocardyl
  • Bedranol
  • Beprane
  • Berkolol
  • Beta-Neg
  • Beta-Propranolol
  • Beta-Tablinen
  • Beta-Timelets
  • Betachron
  • Betalong
  • Cardinol
  • Caridolol
  • Corpendol
  • Deralin
  • Dociton
  • Duranol
  • Efektolol
  • Elbrol
  • Etalong
  • Euprovasin
  • Frekven
  • Inderal
  • Inderal La
  • Inderide
  • Indobloc
  • Innopran XL
  • Intermigran
  • Kemi S
  • Migrastat
  • Obsidan
  • Oposim
  • Prano-Puren
  • Propanix
  • Prophylux
  • Propranolol Hcl Intensol
  • Propranur
  • Proprasylyt
  • Pylapron
  • Rapynogen
  • Reducor
  • Reducor Line
  • Sagittol
  • Servanolol
  • Sloprolol
  • Sumial
  • Tesnol
Brand name mixtures Not Available
Categories
  • Anti-anxiety Agents
  • Antihypertensive Agents
  • Adrenergic Agents
  • Adrenergic beta-Antagonists
  • Vasodilator Agents
  • Antiarrhythmic Agents
  • Anti-Arrhythmia Agents
CAS number 525-66-6
Weight Average: 259.3434
Monoisotopic: 259.157228921
Chemical Formula C16H21NO2
InChI Key InChIKey=AQHHHDLHHXJYJD-UHFFFAOYSA-N
InChI
InChI=1S/C16H21NO2/c1-12(2)17-10-14(18)11-19-16-9-5-7-13-6-3-4-8-15(13)16/h3-9,12,14,17-18H,10-11H2,1-2H3
Plain Text
IUPAC Name
[2-hydroxy-3-(naphthalen-1-yloxy)propyl](propan-2-yl)amine
SMILES
CC(C)NCC(O)COC1=CC=CC2=C1C=CC=C2
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Naphthalenes
Substructures
  • Hydroxy Compounds
  • Naphthalenes
  • 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 prophylaxis of migraine.
Pharmacodynamics Propranolol, the prototype of the beta-adrenergic receptor antagonists, is a competitive, nonselective beta-blocker similar to nadolol without intrinsic sympathomimetic activity. Propanolol is a racemic compound; the l-isomer is responsible for adrenergic blocking activity.
Mechanism of action Propranolol competes with sympathomimetic neurotransmitters such as catecholamines for binding at beta(1)-adrenergic receptors in the heart, inhibiting sympathetic stimulation. This results in a reduction in resting heart rate, cardiac output, systolic and diastolic blood pressure, and reflex orthostatic hypotension.
Absorption Propranolol is almost completely absorbed from the GI tract; however, plasma concentrations attained are quite variable among individuals.
Volume of distribution
  • 4 L
Protein binding More than 90%
Metabolism

Hepatic

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 2D6 4'-hydroxypropanolol 4-hydroxylation 2.73 0
Cytochrome P450 1A2 N-desisopropylpropranolol N-desisopropylation 200 0
Route of elimination Propranolol is extensively metabolized with most metabolites appearing in the urine.
Half life 4 hours
Clearance Not Available
Toxicity Symptoms of overdose include bradycardia, cardiac failure, hypotension, and brochospasm. LD50=565 mg/kg (orally in mice).
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00307 Propranolol Pathway SMP00307
Pharmacoeconomics
Manufacturers
  • Akrimax pharmaceuticals llc
  • Glaxosmithkline llc
  • Actavis elizabeth llc
  • Inwood laboratories inc sub forest laboratories inc
  • Mylan pharmaceuticals inc
  • Par pharmaceutical
  • Upsher smith laboratories inc
  • Roxane laboratories inc
  • App pharmaceuticals llc
  • Baxter healthcare corp anesthesia critical care
  • Bedford laboratories div ben venue laboratories inc
  • Hikma farmaceutica (portugal) sa
  • Sandoz canada inc
  • Smith and nephew solopak div smith and nephew
  • Solopak medical products inc
  • Morton grove pharmaceuticals inc
  • Wyeth ayerst laboratories
  • Clonmel healthcare ltd
  • Duramed pharmaceuticals inc sub barr laboratories inc
  • Interpharm inc
  • Ipca laboratories ltd
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Lederle laboratories div american cyanamid co
  • Mutual pharmaceutical co inc
  • Northstar healthcare holdings ltd
  • Par pharmaceutical inc
  • Pliva inc
  • Purepac pharmaceutical co
  • Sandoz inc
  • Schering corp sub schering plough corp
  • Superpharm corp
  • Teva pharmaceuticals usa inc
  • Vintage pharmaceuticals
  • Warner chilcott div warner lambert co
  • Warner chilcott inc
  • Watson laboratories inc
Packagers
Dosage forms
Form Route Strength
Capsule, extended release Oral
Solution Intravenous
Tablet Oral
Prices
Unit description Cost Unit
Propranolol hcl powder 11.63 USD g
Propranolol 1 mg/ml vial 10.0 USD ml
Inderal la 160 mg capsule 8.41 USD capsule
Inderal LA 160 mg 24 Hour Capsule 7.6 USD capsule
Inderal la 160 mg capsule sa 7.01 USD capsule
Inderal la 120 mg capsule 6.42 USD capsule
Inderal LA 120 mg 24 Hour Capsule 5.8 USD capsule
Inderal la 120 mg capsule sa 5.36 USD capsule
Inderal la 80 mg capsule 5.18 USD capsule
Inderal LA 60 mg 24 Hour Capsule 4.79 USD capsule
Inderal LA 80 mg 24 Hour Capsule 4.68 USD capsule
Inderal la 60 mg capsule 4.43 USD capsule
Inderal la 80 mg capsule sa 4.32 USD capsule
Inderal la 60 mg capsule sa 3.7 USD capsule
Propranolol HCl CR 160 mg 24 Hour Capsule 2.62 USD capsule
InnoPran XL 80 mg 24 Hour Capsule 2.5 USD capsule
InnoPran XL 120 mg 24 Hour Capsule 2.46 USD capsule
Innopran xl 120 mg capsule 2.41 USD capsule
Innopran xl 80 mg capsule 2.41 USD capsule
Inderide 80-25 mg tablet 2.17 USD tablet
Propranolol HCl CR 120 mg 24 Hour Capsule 2.0 USD capsule
Inderide 40-25 mg tablet 1.74 USD tablet
Propranolol HCl CR 80 mg 24 Hour Capsule 1.61 USD capsule
Propranolol HCl CR 60 mg 24 Hour Capsule 1.38 USD capsule
Propranolol HCl 60 mg tablet 1.27 USD tablet
Inderal-La 160 mg Sustained-Release Capsule 1.26 USD capsule
Inderal-La 120 mg Sustained-Release Capsule 1.07 USD capsule
Inderal-La 80 mg Sustained-Release Capsule 0.69 USD capsule
Propranolol HCl 80 mg tablet 0.66 USD tablet
Propranolol-HCTZ 80-25 mg tablet 0.65 USD tablet
Inderal-La 60 mg Sustained-Release Capsule 0.62 USD capsule
Propranolol-HCTZ 40-25 mg tablet 0.61 USD tablet
Propranolol 80 mg tablet 0.58 USD tablet
Propranolol 60 mg tablet 0.56 USD tablet
Propranolol HCl 40 mg tablet 0.53 USD tablet
Propranolol 40 mg tablet 0.45 USD tablet
Propranolol HCl 20 mg tablet 0.36 USD tablet
Propranolol 20 mg tablet 0.33 USD tablet
Apo-Propranolol 120 mg Tablet 0.32 USD tablet
Propranolol HCl 10 mg tablet 0.29 USD tablet
Propranolol 10 mg tablet 0.22 USD tablet
Propranolol HCl 20 mg/5ml Solution 0.11 USD ml
Apo-Propranolol 80 mg Tablet 0.06 USD tablet
Novo-Pranol 80 mg Tablet 0.06 USD tablet
Pms-Propranolol 80 mg Tablet 0.06 USD tablet
Apo-Propranolol 20 mg Tablet 0.04 USD tablet
Apo-Propranolol 40 mg Tablet 0.04 USD tablet
Novo-Pranol 20 mg Tablet 0.04 USD tablet
Novo-Pranol 40 mg Tablet 0.04 USD tablet
Apo-Propranolol 10 mg Tablet 0.02 USD tablet
Novo-Pranol 10 mg Tablet 0.02 USD tablet
Patents
Country Patent Number Approved Expires
United States 6500454 2002-12-31 2022-12-31
Properties
State solid
Melting point 163-164oC
Experimental Properties
Property Value Source
water solubility 0.070 mg/mL (HCl salt) PhysProp
logP 3 PhysProp
Caco2 permeability -4.58 [ADME Research, USCD] BiGG
Predicted Properties
Property Value Source
water solubility 7.94e-02 g/l ALOGPS
logP 3.03 ALOGPS
logP 2.58 ChemAxon Molconvert
logS -3.51 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 6 ChemAxon Molconvert
refractivity 76.83 ChemAxon Molconvert
polarizability 29.98 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Brunet A, Orr SP, Tremblay J, Robertson K, Nader K, Pitman RK: Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder. J Psychiatr Res. 2007 Jun 21;. Pubmed
  2. Ohnishi ST, Sadanaga KK, Katsuoka M, Weidanz WP: Effects of membrane acting-drugs on plasmodium species and sickle cell erythrocytes. Mol Cell Biochem. 1989 Nov 23-Dec 19;91(1-2):159-65. Pubmed
  3. Singh N, Puri SK: Interaction between chloroquine and diverse pharmacological agents in chloroquine resistant Plasmodium yoelii nigeriensis. Acta Trop. 2000 Nov 2;77(2):185-93. Pubmed
  4. Murphy SC, Harrison T, Hamm HE, Lomasney JW, Mohandas N, Haldar K: Erythrocyte G protein as a novel target for malarial chemotherapy. PLoS Med. 2006 Dec;3(12):e528. Pubmed
External Links
Resource Link
KEGG Compound C07407 Link_out
PubChem Compound 4946 Link_out
PubChem Substance 46505387 Link_out
ChemSpider 4777 Link_out
BindingDB 25761 Link_out
ChEBI 8499 Link_out
ChEMBL 8499 Link_out
Therapeutic Targets Database DAP000089 Link_out
Drug Product Database 663719 Link_out
RxList http://www.rxlist.com/cgi/generic/propran.htm Link_out
Drugs.com http://www.drugs.com/propranolol.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Propranolol Link_out
ATC Codes
  • C07AA05
AHFS Codes
  • 24:24.00
PDB Entries Not Available
FDA label show (256.2 KB)
MSDS show (74.7 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Avoid natural licorice.
  • Take with food.
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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Lewis CJ, Gong H, Brown MJ, Harding SE: Overexpression of beta 1-adrenoceptors in adult rat ventricular myocytes enhances CGP 12177A cardiostimulation: implications for ‘putative’ beta 4-adrenoceptor pharmacology. Br J Pharmacol. 2004 Mar;141(5):813-24. Epub 2004 Feb 2. Pubmed
  3. Rouget C, Barthez O, Goirand F, Leroy MJ, Breuiller-Fouche M, Rakotoniaina Z, Guerard P, Morcillo EJ, Advenier C, Sagot P, Cabrol D, Dumas M, Bardou M: Stimulation of the ADRB3 adrenergic receptor induces relaxation of human placental arteries: influence of preeclampsia. Biol Reprod. 2006 Jan;74(1):209-16. Epub 2005 Sep 21. Pubmed
  4. Horinouchi T, Morishima S, Tanaka T, Suzuki F, Tanaka Y, Koike K, Miwa S, Muramatsu I: Different changes of plasma membrane beta-adrenoceptors in rat heart after chronic administration of propranolol, atenolol and bevantolol. Life Sci. 2007 Jul 12;81(5):399-404. Epub 2007 Jun 16. Pubmed
  5. Rezmann-Vitti LA, Louis SN, Nero TL, Jackman GP, Machida CA, Louis WJ: Site-directed mutagenesis of the rat beta1-adrenoceptor. Involvement of Tyr356 (7.43) in (/-)cyanopindolol but not (/-)[125Iodo]cyanopindolol binding. Eur J Med Chem. 2004 Jul;39(7):625-31. Pubmed
  6. Yazawa K, Wang JW, Hao LY, Onoue Y, Kameyama M: Verrucotoxin, a stonefish venom, modulates calcium channel activity in guinea-pig ventricular myocytes. Br J Pharmacol. 2007 Aug;151(8):1198-203. Epub 2007 Jun 18. Pubmed

2. Beta-2 adrenergic receptor

Pharmacological action: unknown
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. Isaza C, Henao J, Ramirez E, Cuesta F, Cacabelos R: Polymorphic variants of the beta2-adrenergic receptor (ADRB2) gene and ADRB2-related propanolol-induced dyslipidemia in the Colombian population. Methods Find Exp Clin Pharmacol. 2005 May;27(4):237-44. Pubmed
  2. Rouget C, Barthez O, Goirand F, Leroy MJ, Breuiller-Fouche M, Rakotoniaina Z, Guerard P, Morcillo EJ, Advenier C, Sagot P, Cabrol D, Dumas M, Bardou M: Stimulation of the ADRB3 adrenergic receptor induces relaxation of human placental arteries: influence of preeclampsia. Biol Reprod. 2006 Jan;74(1):209-16. Epub 2005 Sep 21. Pubmed
  3. Illingworth CJ, Gooding SR, Winn PJ, Jones GA, Ferenczy GG, Reynolds CA: Classical polarization in hybrid QM/MM methods. J Phys Chem A. 2006 May 25;110(20):6487-97. Pubmed
  4. Horinouchi T, Morishima S, Tanaka T, Suzuki F, Tanaka Y, Koike K, Miwa S, Muramatsu I: Different changes of plasma membrane beta-adrenoceptors in rat heart after chronic administration of propranolol, atenolol and bevantolol. Life Sci. 2007 Jul 12;81(5):399-404. Epub 2007 Jun 16. Pubmed
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

3. Beta-3 adrenergic receptor

Pharmacological action: unknown
Actions: antagonist

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

Organism class: human
UniProt ID: P13945 Link_out
Gene: ADRB3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed# Berg T, Piercey BW, Jensen J: Role of beta1-3-adrenoceptors in blood pressure control at rest and during tyramine-induced norepinephrine release in spontaneously hypertensive rats. Hypertension. 2010 May;55(5):1224-30. Epub 2010 Mar 15. Pubmed

4. 5-hydroxytryptamine 1A receptor

Pharmacological action: unknown
Actions: other/unknown

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. Smejkal-Jagar L, Boranic M: Serotonin and serotoninergic agents affect proliferation of normal and transformed lymphoid cells. Immunopharmacol Immunotoxicol. 1995 Feb;17(1):151-62. Pubmed

5. 5-hydroxytryptamine 1B receptor

Pharmacological action: unknown
Actions: other/unknown

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: P28222 Link_out
Gene: HTR1B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Bailey SR, Elliott J: Evidence for different 5-HT1B/1D receptors mediating vasoconstriction of equine digital arteries and veins. Eur J Pharmacol. 1998 Aug 21;355(2-3):175-87. Pubmed
  2. Choppin A, O’Connor SE: Presence of vasoconstrictor 5HT1-like receptors revealed by precontraction of rabbit isolated mesenteric artery. Br J Pharmacol. 1995 Jan;114(2):309-14. Pubmed
Enzymes

1. Cytochrome P450 3A5

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 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

2. Cytochrome P450 2D6

Actions: substrate, inhibitor

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. Yoshimoto K, Echizen H, Chiba K, Tani M, Ishizaki T: Identification of human CYP isoforms involved in the metabolism of propranolol enantiomers—N-desisopropylation is mediated mainly by CYP1A2. Br J Clin Pharmacol. 1995 Apr;39(4):421-31. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. 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
  4. Lewis DF, Modi S, Dickins M: Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82. Pubmed

3. Cytochrome P450 3A7

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 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

4. Cytochrome P450 1A2

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yoshimoto K, Echizen H, Chiba K, Tani M, Ishizaki T: Identification of human CYP isoforms involved in the metabolism of propranolol enantiomers—N-desisopropylation is mediated mainly by CYP1A2. Br J Clin Pharmacol. 1995 Apr;39(4):421-31. Pubmed
  2. Brosen K: Drug interactions and the cytochrome P450 system. The role of cytochrome P450 1A2. Clin Pharmacokinet. 1995;29 Suppl 1:20-5. Pubmed
  3. Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. Pubmed
  4. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  5. 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
  6. Carrillo JA, Benitez J: Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin Pharmacokinet. 2000 Aug;39(2):127-53. Pubmed
  7. Masubuchi Y, Hosokawa S, Horie T, Suzuki T, Ohmori S, Kitada M, Narimatsu S: Cytochrome P450 isozymes involved in propranolol metabolism in human liver microsomes. The role of CYP2D6 as ring-hydroxylase and CYP1A2 as N-desisopropylase. Drug Metab Dispos. 1994 Nov-Dec;22(6):909-15. Pubmed

5. Cytochrome P450 2C19

Actions: substrate

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 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

6. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
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

7. Cytochrome P450 1A1

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P04798 Link_out
Gene: CYP1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed
Transporters

1. Solute carrier family 22 member 2

Actions: inhibitor

Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity

UniProt ID: O15244 Link_out
Gene: SLC22A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Dudley AJ, Bleasby K, Brown CD: The organic cation transporter OCT2 mediates the uptake of beta-adrenoceptor antagonists across the apical membrane of renal LLC-PK cell monolayers. Br J Pharmacol. 2000 Sep;131(1):71-9. Pubmed

2. Multidrug resistance protein 1

Actions: substrate, inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. Pubmed
  2. D’Emanuele A, Jevprasesphant R, Penny J, Attwood D: The use of a dendrimer-propranolol prodrug to bypass efflux transporters and enhance oral bioavailability. J Control Release. 2004 Mar 24;95(3):447-53. Pubmed
Carriers

1. Alpha-1-acid glycoprotein 1

Appears to function in modulating the activity of the immune system during the acute-phase reaction

UniProt ID: P02763 Link_out
Gene: ORM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Ferry DG, Caplan NB, Cubeddu LX: Interaction between antidepressants and alpha 1-adrenergic receptor antagonists on the binding to alpha 1-acid glycoprotein. J Pharm Sci. 1986 Feb;75(2):146-9. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:04

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.