Vardenafil
Identification
- Name
- Vardenafil
- Accession Number
- DB00862
- Description
Vardenafil (Levitra) is an oral therapy for the treatment of erectile dysfunction. It is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Penile erection is a hemodynamic process initiated by the relaxation of smooth muscle in the corpus cavernosum and its associated arterioles. During sexual stimulation, nitric oxide is released from nerve endings and endothelial cells in the corpus cavernosum. Nitric oxide activates the enzyme guanylate cyclase resulting in increased synthesis of cyclic guanosine monophosphate (cGMP) in the smooth muscle cells of the corpus cavernosum. The cGMP in turn triggers smooth muscle relaxation, allowing increased blood flow into the penis, resulting in erection. The tissue concentration of cGMP is regulated by both the rates of synthesis and degradation via phosphodiesterases (PDEs). The most abundant PDE in the human corpus cavernosum is the cGMPspecific phosphodiesterase type 5 (PDE5); therefore, the inhibition of PDE5 enhances erectile function by increasing the amount of cGMP.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Vardenafil (DB00862)
- Weight
- Average: 488.603
Monoisotopic: 488.220574232 - Chemical Formula
- C23H32N6O4S
- Synonyms
- Vardénafil
- Vardenafil
- Vardenafilo
- Vardenafilum
- External IDs
- BAY 389456
- BAY-389456
- BAY38-9456
- DE 19750085 1997
- WO 99/24433 1999
Pharmacology
- Indication
Used for the treatment of erectile dysfunction
- Associated Conditions
- Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More- Pharmacodynamics
Vardenafil is used to treat male erectile dysfunction (impotence) and pulmonary arterial hypertension (PAH). Part of the physiological process of erection involves the release of nitric oxide (NO) in the corpus cavernosum. This then activates the enzyme guanylate cyclase which results in increased levels of cyclic guanosine monophosphate (cGMP), leading to smooth muscle relaxation in the corpus cavernosum, resulting in increased inflow of blood and an erection. Vardenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum. This means that, with vardenafil on board, normal sexual stimulation leads to increased levels of cGMP in the corpus cavernosum which leads to better erections. Without sexual stimulation and no activation of the NO/cGMP system, vardenafil should not cause an erection.
- Mechanism of action
Vardenafil inhibits the cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum located around the penis. Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The inhibition of phosphodiesterase type 5 (PDE5) by vardenafil enhances erectile function by increasing the amount of cGMP.
Target Actions Organism AcGMP-specific 3',5'-cyclic phosphodiesterase inhibitorHumans URetinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma allosteric modulatorHumans URetinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma allosteric modulatorHumans - Absorption
Vardenafil is rapidly absorbed with absolute bioavailability of approximately 15%.
- Volume of distribution
- 208 L
- Protein binding
95%
- Metabolism
Vardenafil is metabolized predominantly by the hepatic enzyme CYP3A4, with contribution from the CYP3A5 and CYP2C isoforms. The major circulating metabolite, M1, results from desethylation at the piperazine moiety of vardenafil. M1 shows a phosphodiesterase selectivity profile similar to that of vardenafil and an in vitro inhibitory potency for PDE5 28% of that of vardenafil.
- Route of elimination
After oral administration, vardenafil is excreted as metabolites predominantly in the feces (approximately 91-95% of administered oral dose) and to a lesser extent in the urine (approximately 2-6% of administered oral dose).
- Half-life
4-5 hours
- Clearance
- 56 L/h
- Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More- Toxicity
Symptoms of overdose include vision changes and back and muscle pain.
- Affected organisms
- Humans and other mammals
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Unlock Additional DataAbametapir The serum concentration of Vardenafil can be increased when it is combined with Abametapir. Abatacept The metabolism of Vardenafil can be increased when combined with Abatacept. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Vardenafil. Abiraterone The metabolism of Vardenafil can be decreased when combined with Abiraterone. Acalabrutinib The metabolism of Vardenafil can be decreased when combined with Acalabrutinib. Acebutolol The risk or severity of QTc prolongation can be increased when Vardenafil is combined with Acebutolol. Acetaminophen The metabolism of Vardenafil can be decreased when combined with Acetaminophen. Acetazolamide The metabolism of Vardenafil can be decreased when combined with Acetazolamide. Acrivastine The risk or severity of QTc prolongation can be increased when Vardenafil is combined with Acrivastine. Adalimumab The metabolism of Vardenafil can be increased when combined with Adalimumab. Additional Data Available- Extended DescriptionExtended DescriptionAvailable for Purchase
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more - SeveritySeverityAvailable for Purchase
A severity rating for each drug interaction, from minor to major.
Learn more - Evidence LevelEvidence LevelAvailable for Purchase
A rating for the strength of the evidence supporting each drug interaction.
Learn more - ActionActionAvailable for Purchase
An effect category for each drug interaction. Know how this interaction affects the subject drug.
Learn more
- Food Interactions
- Avoid grapefruit products. Vardenafil is metabolized by CYP3A4, and grapefruit products are CYP3A4 inhibitors; therefore, coadministration may increase serum levels of vardenafil and result in increased hypotension. .
- Take with or without food.
Products
- Product Ingredients
Ingredient UNII CAS InChI Key Vardenafil hydrochloride 5M8S2CU0TS 330808-88-3 FBCDRHDULQYRTB-UHFFFAOYSA-N - Product Images
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Unlock Additional DataLevitra Tablet, film coated 20 mg Oral Bayer Ag 2016-09-08 Not applicable EU 
Levitra Tablet 10 mg Oral Bayer 2004-03-17 Not applicable Canada 
Levitra Tablet, film coated 5 mg/1 Oral Schering Plough 2008-05-15 2013-07-01 US 
Levitra Tablet, film coated 10 mg Oral Bayer Ag 2016-09-08 Not applicable EU Levitra Tablet, film coated 10 mg Oral Bayer Ag 2016-09-08 Not applicable EU Levitra Tablet, film coated 20 mg/1 Oral Aphena Pharma Solutions Tennessee, Inc. 2008-05-15 Not applicable US Levitra Tablet, orally disintegrating 10 mg Oral Bayer Ag 2016-09-08 Not applicable EU Levitra Tablet, film coated 20 mg/1 Oral KAISER FOUNDATION HOSPITALS 2011-10-28 2014-09-30 US Levitra Tablet, film coated 5 mg/1 Oral GlaxoSmithKline LLC 2003-04-23 Not applicable US Levitra Tablet, film coated 10 mg/1 Oral Aphena Pharma Solutions Tennessee, Inc. 2011-04-22 Not applicable US 
Additional Data Available- Application NumberApplication NumberAvailable for Purchase
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more - Product CodeProduct CodeAvailable for Purchase
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
Learn more
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Unlock Additional DataAg-vardenafil Tablet Oral Angita Pharma Inc. Not applicable Not applicable Canada Ag-vardenafil Tablet Oral Angita Pharma Inc. Not applicable Not applicable Canada Ag-vardenafil Tablet Oral Angita Pharma Inc. Not applicable Not applicable Canada Apo-vardenafil Tablet Oral Apotex Corporation 2018-12-21 Not applicable Canada Apo-vardenafil Tablet Oral Apotex Corporation 2018-12-21 Not applicable Canada Apo-vardenafil Tablet Oral Apotex Corporation 2018-12-21 Not applicable Canada Jamp-vardenafil Tablet Oral Jamp Pharma Corporation 2018-11-01 Not applicable Canada Jamp-vardenafil Tablet Oral Jamp Pharma Corporation 2018-11-01 Not applicable Canada Jamp-vardenafil Tablet Oral Jamp Pharma Corporation 2018-11-01 Not applicable Canada Jamp-vardenafil ODT Tablet, orally disintegrating Oral Jamp Pharma Corporation 2019-06-06 Not applicable Canada Additional Data Available- Application NumberApplication NumberAvailable for Purchase
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more - Product CodeProduct CodeAvailable for Purchase
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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Categories
- ATC Codes
- G04BE09 — Vardenafil
- Drug Categories
- Cardiovascular Agents
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 Substrates
- Drugs Used in Erectile Dysfunction
- Enzyme Inhibitors
- Genito Urinary System and Sex Hormones
- Imidazoles
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- Phosphodiesterase 5 Inhibitors
- Phosphodiesterase Inhibitors
- Piperazines
- Potential QTc-Prolonging Agents
- QTc Prolonging Agents
- Urological Agents
- Urologicals
- Vasodilating Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Benzenesulfonamides
- Direct Parent
- Benzenesulfonamides
- Alternative Parents
- Benzenesulfonyl compounds / Phenoxy compounds / Phenol ethers / N-alkylpiperazines / Alkyl aryl ethers / Organosulfonamides / N-substituted imidazoles / 1,2,4-triazines / Sulfonyls / Heteroaromatic compounds show 5 more
- Substituents
- 1,2,4-triazine / 1,4-diazinane / Alkyl aryl ether / Amine / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenesulfonamide / Benzenesulfonyl group / Ether show 23 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- N-alkylpiperazine, imidazotriazine, N-sulfonylpiperazine (CHEBI:46295)
Chemical Identifiers
- UNII
- UCE6F4125H
- CAS number
- 224785-90-4
- InChI Key
- SECKRCOLJRRGGV-UHFFFAOYSA-N
- InChI
- InChI=1S/C23H32N6O4S/c1-5-8-20-24-16(4)21-23(30)25-22(26-29(20)21)18-15-17(9-10-19(18)33-7-3)34(31,32)28-13-11-27(6-2)12-14-28/h9-10,15H,5-8,11-14H2,1-4H3,(H,25,26,30)
- IUPAC Name
- 2-{2-ethoxy-5-[(4-ethylpiperazin-1-yl)sulfonyl]phenyl}-5-methyl-7-propyl-1H,4H-imidazo[4,3-f][1,2,4]triazin-4-one
- SMILES
- CCCC1=NC(C)=C2N1NC(=NC2=O)C1=C(OCC)C=CC(=C1)S(=O)(=O)N1CCN(CC)CC1
References
- Synthesis Reference
Yogesh S. Deshpande, Sandra Brueck, Julia Schulze Nahrup, Birgit Schnitter, Ganesh Gat, Javed Hussain, "PROCESS FOR THE PREPARATION OF A MEDICAMENT COMPRISING VARDENAFIL HYDROCHLORIDE TRIHYDRATE." U.S. Patent US20100159003, issued June 24, 2010.
US20100159003- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0015000
- KEGG Drug
- D08668
- PubChem Compound
- 110634
- PubChem Substance
- 46506777
- ChemSpider
- 99300
- BindingDB
- 50088373
- 306674
- ChEBI
- 46295
- ChEMBL
- CHEMBL1520
- ZINC
- ZINC000018324776
- Therapeutic Targets Database
- DAP000414
- PharmGKB
- PA10229
- PDBe Ligand
- VDN
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Vardenafil
- AHFS Codes
- 24:12.12 — Phosphodiesterase Type 5 Inhibitors
- PDB Entries
- 1uho / 1xot / 1xp0 / 3b2r / 7jsn
- FDA label
- Download (535 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Acquired Immune Deficiency Syndrome (AIDS) 1 4 Completed Treatment Arterial Hypertension / Endothelial Dysfunction / Erectile Dysfunction 1 4 Completed Treatment Erectile Dysfunction 15 4 Completed Treatment Erectile Dysfunction / Metabolic Syndromes 1 4 Completed Treatment Erectile Dysfunction / Sexual Dysfunctions 1 4 Completed Treatment Erectile Dysfunction / Spinal Cord Injuries (SCI) 1 4 Completed Treatment Safety 1 4 Terminated Treatment Hypogonadism / Type 2 Diabetes Mellitus 1 4 Unknown Status Treatment Erectile Dysfunction 2 4 Unknown Status Treatment Erectile Dysfunction / Hypogonadotrophic Males 1
Pharmacoeconomics
- Manufacturers
- Bayer healthcare pharmaceuticals inc
- Packagers
- A-S Medication Solutions LLC
- Bayer Healthcare
- Bryant Ranch Prepack
- Kaiser Foundation Hospital
- Lake Erie Medical and Surgical Supply
- Murfreesboro Pharmaceutical Nursing Supply
- Physicians Total Care Inc.
- Prepak Systems Inc.
- Redpharm Drug
- Schering Corp.
- Va Cmop Dallas
- Dosage Forms
Form Route Strength Tablet, orally disintegrating Oral Tablet, film coated Oral 10 mg Tablet, film coated Oral 10 mg/1 Tablet, film coated Oral 2.5 mg/1 Tablet, film coated Oral 20 mg/1 Tablet, film coated Oral 20 mg Tablet, film coated Oral 5 mg/1 Tablet, film coated Oral 5 mg Tablet, orally disintegrating Oral 10 mg Tablet, soluble Oral 10 MG Tablet Oral 10 mg Tablet, coated Oral 10 mg Tablet Oral 20 mg Tablet, coated Oral 20 mg Tablet Oral 5 mg Tablet, coated Oral 5 mg Tablet Oral Tablet, orally disintegrating Oral 10 mg/1 Tablet, orally disintegrating Oral 11.85 mg/1 Tablet Oral 11.85 mg/1 Tablet Oral 10 mg/1 Tablet Oral 2.5 mg/1 Tablet Oral 20 mg/1 Tablet Oral 5 mg/1 - Prices
Unit description Cost Unit Levitra 10 mg tablet 19.04USD tablet Levitra 20 mg tablet 19.04USD tablet Levitra 5 mg tablet 19.04USD tablet Levitra 2.5 mg tablet 18.66USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region Unlock Additional DataCA2309332 No 2002-12-03 2018-10-31 Canada US6362178 No 2002-03-26 2018-10-31 US US7696206 No 2010-04-13 2018-10-31 US US8273876 No 2012-09-25 2027-07-23 US US8841446 No 2014-09-23 2023-07-03 US US8613950 No 2013-12-24 2028-12-23 US Additional Data Available- Filed OnFiled OnAvailable for Purchase
The date on which a patent was filed with the relevant government.
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Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 192 °C Not Available water solubility 0.11 mg/mL (HCl salt) Not Available logP 1.4 Not Available - Predicted Properties
Property Value Source Water Solubility 0.325 mg/mL ALOGPS logP 2.18 ALOGPS logP 1.33 ChemAxon logS -3.2 ALOGPS pKa (Strongest Acidic) 8.01 ChemAxon pKa (Strongest Basic) 6.21 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 8 ChemAxon Hydrogen Donor Count 1 ChemAxon Polar Surface Area 109.13 Å2 ChemAxon Rotatable Bond Count 7 ChemAxon Refractivity 142.71 m3·mol-1 ChemAxon Polarizability 53.22 Å3 ChemAxon Number of Rings 4 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule Yes ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.6682 Caco-2 permeable + 0.5502 P-glycoprotein substrate Substrate 0.7415 P-glycoprotein inhibitor I Inhibitor 0.6976 P-glycoprotein inhibitor II Inhibitor 0.8552 Renal organic cation transporter Non-inhibitor 0.6975 CYP450 2C9 substrate Non-substrate 0.6386 CYP450 2D6 substrate Substrate 0.7909 CYP450 3A4 substrate Substrate 0.697 CYP450 1A2 substrate Non-inhibitor 0.8215 CYP450 2C9 inhibitor Inhibitor 0.7426 CYP450 2D6 inhibitor Non-inhibitor 0.8464 CYP450 2C19 inhibitor Non-inhibitor 0.7472 CYP450 3A4 inhibitor Inhibitor 0.8857 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7205 Ames test Non AMES toxic 0.5748 Carcinogenicity Non-carcinogens 0.6141 Biodegradation Not ready biodegradable 0.8875 Rat acute toxicity 2.6208 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8367 hERG inhibition (predictor II) Inhibitor 0.7696
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available LC-MS/MS Spectrum - LC-ESI-QFT , negative LC-MS/MS splash10-000i-0040900000-a78a646244f2fb1f6276 MS/MS Spectrum - , positive LC-MS/MS splash10-000f-0011900000-88f62b9a8f7aec917a41 MS/MS Spectrum - , positive LC-MS/MS splash10-0002-0092000000-cf98ecae287c01370dbc
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Metal ion binding
- Specific Function
- Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP (PubMed:9714779, ...
- Gene Name
- PDE5A
- Uniprot ID
- O76074
- Uniprot Name
- cGMP-specific 3',5'-cyclic phosphodiesterase
- Molecular Weight
- 99984.14 Da
References
- Blount MA, Zoraghi R, Ke H, Bessay EP, Corbin JD, Francis SH: A 46-amino acid segment in phosphodiesterase-5 GAF-B domain provides for high vardenafil potency over sildenafil and tadalafil and is involved in phosphodiesterase-5 dimerization. Mol Pharmacol. 2006 Nov;70(5):1822-31. Epub 2006 Aug 22. [PubMed:16926278]
- Carrier S: Pharmacology of phosphodiesterase 5 inhibitors. Can J Urol. 2003 Feb;10 Suppl 1:12-6. [PubMed:12625845]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
- Kim NN, Huang YH, Goldstein I, Bischoff E, Traish AM: Inhibition of cyclic GMP hydrolysis in human corpus cavernosum smooth muscle cells by vardenafil, a novel, selective phosphodiesterase type 5 inhibitor. Life Sci. 2001 Sep 28;69(19):2249-56. [PubMed:11669467]
- Saenz de Tejada I, Angulo J, Cuevas P, Fernandez A, Moncada I, Allona A, Lledo E, Korschen HG, Niewohner U, Haning H, Pages E, Bischoff E: The phosphodiesterase inhibitory selectivity and the in vitro and in vivo potency of the new PDE5 inhibitor vardenafil. Int J Impot Res. 2001 Oct;13(5):282-90. [PubMed:11890515]
- Scheen AJ: [Medication of the month. Vardenafil (Levitra)]. Rev Med Liege. 2003 Sep;58(9):576-9. [PubMed:14626653]
- Sung BJ, Hwang KY, Jeon YH, Lee JI, Heo YS, Kim JH, Moon J, Yoon JM, Hyun YL, Kim E, Eum SJ, Park SY, Lee JO, Lee TG, Ro S, Cho JM: Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. Nature. 2003 Sep 4;425(6953):98-102. [PubMed:12955149]
- Wang H, Ye M, Robinson H, Francis SH, Ke H: Conformational variations of both phosphodiesterase-5 and inhibitors provide the structural basis for the physiological effects of vardenafil and sildenafil. Mol Pharmacol. 2008 Jan;73(1):104-10. Epub 2007 Oct 24. [PubMed:17959709]
- Zoraghi R, Francis SH, Corbin JD: Critical amino acids in phosphodiesterase-5 catalytic site that provide for high-affinity interaction with cyclic guanosine monophosphate and inhibitors. Biochemistry. 2007 Nov 27;46(47):13554-63. Epub 2007 Nov 3. [PubMed:17979301]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Allosteric modulator
- General Function
- Enzyme inhibitor activity
- Specific Function
- Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones.
- Gene Name
- PDE6G
- Uniprot ID
- P18545
- Uniprot Name
- Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
- Molecular Weight
- 9643.09 Da
References
- Zhang XJ, Cahill KB, Elfenbein A, Arshavsky VY, Cote RH: Direct allosteric regulation between the GAF domain and catalytic domain of photoreceptor phosphodiesterase PDE6. J Biol Chem. 2008 Oct 31;283(44):29699-705. doi: 10.1074/jbc.M803948200. Epub 2008 Sep 8. [PubMed:18779324]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Allosteric modulator
- General Function
- Enzyme inhibitor activity
- Specific Function
- Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones.
- Gene Name
- PDE6H
- Uniprot ID
- Q13956
- Uniprot Name
- Retinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
- Molecular Weight
- 9074.36 Da
References
- Zhang XJ, Cahill KB, Elfenbein A, Arshavsky VY, Cote RH: Direct allosteric regulation between the GAF domain and catalytic domain of photoreceptor phosphodiesterase PDE6. J Biol Chem. 2008 Oct 31;283(44):29699-705. doi: 10.1074/jbc.M803948200. Epub 2008 Sep 8. [PubMed:18779324]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- 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 react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Sheweita SA, Wally M, Hassan M: Erectile Dysfunction Drugs Changed the Protein Expressions and Activities of Drug-Metabolising Enzymes in the Liver of Male Rats. Oxid Med Cell Longev. 2016;2016:4970906. doi: 10.1155/2016/4970906. Epub 2016 Oct 9. [PubMed:27800121]
- Huang SA, Lie JD: Phosphodiesterase-5 (PDE5) Inhibitors In the Management of Erectile Dysfunction. P T. 2013 Jul;38(7):407-19. [PubMed:24049429]
- Vardenafil FDA [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxygen binding
- Specific Function
- 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 un...
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Huang SA, Lie JD: Phosphodiesterase-5 (PDE5) Inhibitors In the Management of Erectile Dysfunction. P T. 2013 Jul;38(7):407-19. [PubMed:24049429]
- Ku HY, Ahn HJ, Seo KA, Kim H, Oh M, Bae SK, Shin JG, Shon JH, Liu KH: The contributions of cytochromes P450 3A4 and 3A5 to the metabolism of the phosphodiesterase type 5 inhibitors sildenafil, udenafil, and vardenafil. Drug Metab Dispos. 2008 Jun;36(6):986-90. doi: 10.1124/dmd.107.020099. Epub 2008 Feb 28. [PubMed:18308836]
- Bayer monograph, Levitra [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Ding PR, Tiwari AK, Ohnuma S, Lee JW, An X, Dai CL, Lu QS, Singh S, Yang DH, Talele TT, Ambudkar SV, Chen ZS: The phosphodiesterase-5 inhibitor vardenafil is a potent inhibitor of ABCB1/P-glycoprotein transporter. PLoS One. 2011 Apr 28;6(4):e19329. doi: 10.1371/journal.pone.0019329. [PubMed:21552528]
- Choi MK, Song IS: Characterization of efflux transport of the PDE5 inhibitors, vardenafil and sildenafil. J Pharm Pharmacol. 2012 Aug;64(8):1074-83. doi: 10.1111/j.2042-7158.2012.01498.x. Epub 2012 Mar 16. [PubMed:22775210]
- Chen JJ, Sun YL, Tiwari AK, Xiao ZJ, Sodani K, Yang DH, Vispute SG, Jiang WQ, Chen SD, Chen ZS: PDE5 inhibitors, sildenafil and vardenafil, reverse multidrug resistance by inhibiting the efflux function of multidrug resistance protein 7 (ATP-binding Cassette C10) transporter. Cancer Sci. 2012 Aug;103(8):1531-7. doi: 10.1111/j.1349-7006.2012.02328.x. Epub 2012 Jul 6. [PubMed:22578167]
- Tiwari AK, Chen ZS: Repurposing phosphodiesterase-5 inhibitors as chemoadjuvants. Front Pharmacol. 2013 Jun 25;4:82. doi: 10.3389/fphar.2013.00082. eCollection 2013. [PubMed:23805103]
Drug created on June 13, 2005 07:24 / Updated on January 18, 2021 16:18