Identification

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates
Name
Vardenafil
Accession Number
DB00862  (APRD00699)
Type
Small Molecule
Groups
Approved
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.

Structure
Thumb
Synonyms
  • Vardénafil
  • Vardenafil
  • Vardenafilo
  • Vardenafilum
External IDs
BAY 389456 / BAY-389456 / BAY38-9456 / DE 19750085 1997 / WO 99/24433 1999
Product Ingredients
IngredientUNIICASInChI Key
Vardenafil hydrochloride5M8S2CU0TS330808-88-3FBCDRHDULQYRTB-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LevitraTablet, film coated10 mgOralBayer Ag2003-03-06Not applicableEu
LevitraTablet, film coated10 mg/1OralAphena Pharma Solutions Tennessee, Inc.2008-05-15Not applicableUs
LevitraTablet, orally disintegrating10 mgOralBayer Ag2003-03-06Not applicableEu
LevitraTablet, film coated20 mg/1OralPhysicians Total Care, Inc.2004-01-27Not applicableUs
LevitraTablet20 mgOralBayer2004-03-17Not applicableCanada
LevitraTablet, film coated5 mg/1OralGlaxoSmithKline LLC2003-04-23Not applicableUs
LevitraTablet, film coated20 mgOralBayer Ag2003-03-06Not applicableEu
LevitraTablet, film coated20 mg/1Oralbryant ranch prepack2008-05-15Not applicableUs
LevitraTablet, film coated5 mgOralBayer Ag2003-03-06Not applicableEu
LevitraTablet, film coated2.5 mg/1OralSchering Plough2008-05-152013-07-01Us
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ag-vardenafilTabletOralAngita Pharma Inc.Not applicableNot applicableCanada
Ag-vardenafilTabletOralAngita Pharma Inc.Not applicableNot applicableCanada
Ag-vardenafilTabletOralAngita Pharma Inc.Not applicableNot applicableCanada
Apo-vardenafilTabletOralApotex Corporation2018-12-21Not applicableCanada
Apo-vardenafilTabletOralApotex Corporation2018-12-21Not applicableCanada
Apo-vardenafilTabletOralApotex Corporation2018-12-21Not applicableCanada
Jamp-vardenafilTabletOralJamp Pharma Corporation2018-11-01Not applicableCanada
Jamp-vardenafilTabletOralJamp Pharma Corporation2018-11-01Not applicableCanada
Jamp-vardenafilTabletOralJamp Pharma Corporation2018-11-01Not applicableCanada
Jamp-vardenafil ODTTablet, orally disintegratingOralJamp Pharma Corporation2019-06-06Not applicableCanada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Categories
UNII
UCE6F4125H
CAS number
224785-90-4
Weight
Average: 488.603
Monoisotopic: 488.220574232
Chemical Formula
C23H32N6O4S
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

Pharmacology

Indication

Used for the treatment of erectile dysfunction

Associated Conditions
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.

TargetActionsOrganism
AcGMP-specific 3',5'-cyclic phosphodiesterase
inhibitor
Humans
URetinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
allosteric modulator
Humans
URetinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
allosteric modulator
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

Learn more
Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

Learn more
Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

Learn more
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
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.
DrugInteraction
6-Deoxyerythronolide BThe metabolism of Vardenafil can be decreased when combined with 6-Deoxyerythronolide B.
7-ethyl-10-hydroxycamptothecinThe metabolism of Vardenafil can be decreased when combined with 7-ethyl-10-hydroxycamptothecin.
9-aminocamptothecinThe metabolism of Vardenafil can be decreased when combined with 9-aminocamptothecin.
AbataceptThe metabolism of Vardenafil can be increased when combined with Abatacept.
AbemaciclibThe serum concentration of Vardenafil can be increased when it is combined with Abemaciclib.
AbexinostatThe risk or severity of QTc prolongation can be increased when Vardenafil is combined with Abexinostat.
AcalabrutinibThe metabolism of Vardenafil can be decreased when combined with Acalabrutinib.
AcebutololVardenafil may increase the antihypertensive activities of Acebutolol.
AcepromazineThe risk or severity of hypotension, dyspepsia, and headache can be increased when Vardenafil is combined with Acepromazine.
AceprometazineThe risk or severity of QTc prolongation can be increased when Vardenafil is combined with Aceprometazine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
Not Available

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
ChEBI
46295
ChEMBL
CHEMBL1520
Therapeutic Targets Database
DAP000414
PharmGKB
PA10229
HET
VDN
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Vardenafil
ATC Codes
G04BE09 — Vardenafil
AHFS Codes
  • 24:12.12 — Phosphodiesterase Type 5 Inhibitors
PDB Entries
1uho / 1xot / 1xp0 / 3b2r
FDA label
Download (535 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0TerminatedTreatmentBrain Metastasis / Gliomas / Neoplasms, Brain1
1CompletedNot AvailableErectile Dysfunction2
1CompletedBasic ScienceGenetic Polymorphic CYP3A5 / Healthy Volunteers / Pharmacokinetics of Three PDE5Is1
1CompletedTreatmentIschemia-Reperfusion Injury1
1, 2RecruitingTreatmentErectile Dysfunction1
2CompletedSupportive CareEndothelial Dysfunction / Erectile Dysfunction / Type 2 Diabetes Mellitus1
2CompletedTreatmentBenign Prostatic Hyperplasia (BPH)1
2CompletedTreatmentBenign Prostatic Hypertrophy1
2CompletedTreatmentDetrusor Overactivity / Urinary Bladder, Overactive1
2CompletedTreatmentErectile Dysfunction2
2CompletedTreatmentTinnitus1
2TerminatedTreatmentCystic Fibrosis (CF)1
2, 3CompletedTreatmentErectile Dysfunction1
2, 3CompletedTreatmentRaynaud's Phenomenon1
3CompletedTreatmentDepression / Erectile Dysfunction1
3CompletedTreatmentDiabetes Mellitus (DM) / Erectile Dysfunction1
3CompletedTreatmentErectile Dysfunction17
3CompletedTreatmentErectile Dysfunction / Sexual Dysfunction, Physiological1
3CompletedTreatmentErectile Dysfunction / Sexual Dysfunctions / Spinal Cord Injuries (SCI)1
3CompletedTreatmentPulmonary Hypertension (PH)1
4CompletedNot AvailableErectile Dysfunction1
4CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS)1
4CompletedTreatmentArterial Hypertension / Endothelial Dysfunction / Erectile Dysfunction1
4CompletedTreatmentErectile Dysfunction15
4CompletedTreatmentErectile Dysfunction / Metabolic Syndromes1
4CompletedTreatmentErectile Dysfunction / Sexual Dysfunctions1
4CompletedTreatmentErectile Dysfunction / Spinal Cord Injuries (SCI)1
4CompletedTreatmentSafety1
4RecruitingTreatmentErectile Dysfunction / Liver Cirrhosis1
4TerminatedTreatmentHypogonadism / Type 2 Diabetes Mellitus1
4Unknown StatusTreatmentErectile Dysfunction2
4Unknown StatusTreatmentErectile Dysfunction / Hypogonadotrophic Males1
4Unknown StatusTreatmentPulmonary Arterial Hypertension (PAH)2
Not AvailableCompletedNot AvailableErectile Dysfunction4
Not AvailableCompletedTreatmentErectile Dysfunction / Prostatic Hyperplasia1
Not AvailableTemporarily Not AvailableNot AvailableCoronary Artery Disease / Therapy Refractory Myocardial Ischemia / Unsuitable for Surgical or Percutaneous Revascularisation1
Not AvailableTerminatedNot AvailableErectile Dysfunction1

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
FormRouteStrength
Tablet, orally disintegratingOral
TabletOral10 mg
TabletOral20 mg
TabletOral5 mg
Tablet, film coatedOral10 mg
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral2.5 mg/1
Tablet, film coatedOral20 mg
Tablet, film coatedOral20 mg/1
Tablet, film coatedOral5 mg
Tablet, film coatedOral5 mg/1
Tablet, orally disintegratingOral10 mg
TabletOral
Tablet, orally disintegratingOral10 mg/1
Tablet, orally disintegratingOral11.85 mg/1
TabletOral10 mg/1
TabletOral2.5 mg/1
TabletOral20 mg/1
TabletOral5 mg/1
Prices
Unit descriptionCostUnit
Levitra 10 mg tablet19.04USD tablet
Levitra 20 mg tablet19.04USD tablet
Levitra 5 mg tablet19.04USD tablet
Levitra 2.5 mg tablet18.66USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2309332No2002-12-032018-10-31Canada
US6362178No2002-03-262018-10-31Us
US7696206No2010-04-132018-10-31Us
US8273876No2012-09-252027-07-23Us
US8841446No2014-09-232023-07-03Us
US8613950No2013-12-242028-12-23Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)192 °CNot Available
water solubility0.11 mg/mL (HCl salt)Not Available
logP1.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.325 mg/mLALOGPS
logP2.18ALOGPS
logP1.33ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)8.01ChemAxon
pKa (Strongest Basic)6.21ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area109.13 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity142.71 m3·mol-1ChemAxon
Polarizability53.22 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.6682
Caco-2 permeable+0.5502
P-glycoprotein substrateSubstrate0.7415
P-glycoprotein inhibitor IInhibitor0.6976
P-glycoprotein inhibitor IIInhibitor0.8552
Renal organic cation transporterNon-inhibitor0.6975
CYP450 2C9 substrateNon-substrate0.6386
CYP450 2D6 substrateSubstrate0.7909
CYP450 3A4 substrateSubstrate0.697
CYP450 1A2 substrateNon-inhibitor0.8215
CYP450 2C9 inhibitorInhibitor0.7426
CYP450 2D6 inhibitorNon-inhibitor0.8464
CYP450 2C19 inhibitorNon-inhibitor0.7472
CYP450 3A4 inhibitorInhibitor0.8857
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7205
Ames testNon AMES toxic0.5748
CarcinogenicityNon-carcinogens0.6141
BiodegradationNot ready biodegradable0.8875
Rat acute toxicity2.6208 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8367
hERG inhibition (predictor II)Inhibitor0.7696
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
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
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-000i-0040900000-a78a646244f2fb1f6276
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000f-0011900000-88f62b9a8f7aec917a41
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0092000000-cf98ecae287c01370dbc

Taxonomy

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
Benzenesulfonamide / Benzenesulfonyl group / Phenoxy compound / Phenol ether / Alkyl aryl ether / N-alkylpiperazine / 1,4-diazinane / N-substituted imidazole / Piperazine / Organosulfonic acid amide
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
N-alkylpiperazine, imidazotriazine, N-sulfonylpiperazine (CHEBI:46295)

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
  1. 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]
  2. Carrier S: Pharmacology of phosphodiesterase 5 inhibitors. Can J Urol. 2003 Feb;10 Suppl 1:12-6. [PubMed:12625845]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  4. 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]
  5. 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]
  6. Scheen AJ: [Medication of the month. Vardenafil (Levitra)]. Rev Med Liege. 2003 Sep;58(9):576-9. [PubMed:14626653]
  7. 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]
  8. 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]
  9. 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
  1. 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
  1. 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
  1. 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]
  2. Huang SA, Lie JD: Phosphodiesterase-5 (PDE5) Inhibitors In the Management of Erectile Dysfunction. P T. 2013 Jul;38(7):407-19. [PubMed:24049429]
  3. 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
  1. Huang SA, Lie JD: Phosphodiesterase-5 (PDE5) Inhibitors In the Management of Erectile Dysfunction. P T. 2013 Jul;38(7):407-19. [PubMed:24049429]
  2. 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]
  3. Bayer monograph, Levitra [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
  1. 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]
  2. 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]
  3. 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]
  4. 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 November 19, 2019 16:31