PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
sildenafil

2D structure

Overview

Generic Names: Sildenafil Citrate
Trade Names: Revatio; Sildenafil Viagra; Viagra
PharmGKB Accession Id: PA451346

Description

Sildenafil (in citrate form), sold under the names Viagra, Revatio and under various other names, is a drug used to treat male erectile dysfunction (impotence) and pulmonary arterial hypertension (PAH), developed by the pharmaceutical company Pfizer. Its primary competitors on the market are tadalafil (Cialis), and vardenafil (Levitra). Wikipedia (source: Drug Bank)

Indication

For the treatment of erectile dysfunction (source: Drug Bank)

ATC Therapeutic Category

  • G04BE:Drugs used in erectile dysfunction

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Sildenafil 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 Sildenafil enhances erectile function by increasing the amount of cGMP. (source: Drug Bank)

Pharmacology

Sildenafil 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. Sildenafil 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 Sildenafil 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, Sildenafil should not cause an erection. (source: Drug Bank)

Food Interactions

Take on empty stomach: 1 hour before or 2 hours after meals. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic (source: Drug Bank)

Protein Binding

96% (source: Drug Bank)

Absorption

~40% (source: Drug Bank)

Isomeric SMILES Code:

CCCc1c2c(c(=O)[nH]c(n2)c3cc(ccc3OCC)S(=O)(=O)N4CCN(CC4)C)n(n1)C (source: Drug Bank)

Curated Annotations (Curated Annotation)

  1. rs5443 at chr12:6825136 in GNB3, USP5
    This variant is associated with sildenafil response for erectile dysfunction patients.
    Variant Name:
    GNB3:825C>T; GNB3:Ser275Ser
    Related Drugs:
    sildenafil
    Related Diseases:
    Erectile Dysfunction
    Evidence:
    PMID:12576843
  2. rs1799752 at chr17:58919622 in ACE
    This variant is one of the insertion/deletion variant in intron 16 of the ACE gene. It is associated with sildenafil response for erectile dysfunction patients. Patients with D allele have elevated ACE serum concentrations and are less likely to respond to sildenafil.
    Variant Name:
    ACE:I/D
    Related Drugs:
    sildenafil
    Related Diseases:
    Erectile Dysfunction
    Evidence:
    PMID:12837457
  3. rs13447447 at chr17:58919624 in ACE
    This variant is one of the insertion/deletion variant in intron 16 of the ACE gene. It is associated with sildenafil response for erectile dysfunction patients. Patients with D allele have elevated ACE serum concentrations and are less likely to respond to sildenafil.
    Variant Name:
    ACE:I/D
    Related Drugs:
    sildenafil
    Related Diseases:
    Erectile Dysfunction
    Evidence:
    PMID:12837457
  4. rs4340 at chr17:58919624 in ACE
    This variant is one of the insertion/deletion variant in intron 16 of the ACE gene. It is associated with sildenafil response for erectile dysfunction patients. Patients with D allele have elevated ACE serum concentrations and are less likely to respond to sildenafil.
    Variant Name:
    ACE:I/D
    Related Drugs:
    sildenafil
    Related Diseases:
    Erectile Dysfunction
    Evidence:
    PMID:12837457
  5. rs4646994 at chr17:58919632 in ACE
    This variant is one of the insertion/deletion variant in intron 16 of the ACE gene. It is associated with sildenafil response for erectile dysfunction patients. Patients with D allele have elevated ACE serum concentrations and are less likely to respond to sildenafil.
    Variant Name:
    ACE:I/D
    Related Drugs:
    sildenafil
    Related Diseases:
    Erectile Dysfunction
    Evidence:
    PMID:12837457
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Not annotated
ABCC5
  •   
  •   
  •   
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
ACE
  •   
  •   
  •   
  •   
  •   
Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C9
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
CYP3A
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A4
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A5
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
GNB3
  •   
  •   
  •   
  •   
  •   
Variants
Phenotype data available Genotype Data Available Literature annotations available Not annotated
NOS3
  •   
  •   
  •   
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
NR1I2
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data Genotype Data Available No literature annotations Not annotated
USP5
  •   
  •   
  •   
  •   
  •   
Variants

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
PDE2A Uncurated Annotation (source: Drug Bank)
PDE5A Uncurated Annotation (source: Drug Bank)

A list of non-curated publications that mention this drug along with other drugs is available.

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Alopecia
  • CO
  • PD
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Diarrhea
  • CO
  • PD
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Drug Toxicity
  • CO
  • PD
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Erectile Dysfunction
  •   
  •   
  •   
  • FA
  •   
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Hypersensitivity
  • CO
  • PD
  •   
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
Hypertension
  • CO
  • PD
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Hypertension, Pulmonary
  • CO
  • PD
  •   
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
Neoplasms
  • CO
  • PD
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Skin Diseases
  • CO
  • PD
  •   
  •   
  •   
Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

  1. Physicochemical determinants of human renal clearance

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00203
KEGG Compound ID:
C07259
KEGG Drug ID:
D02229
PubChem Compound ID:
5212
PubChem Substance ID:
205034

Common Searches

Search PubMed
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Search PubChem
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Non-Curated Publications

A list of non-curated publications that mention this drug is available.

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
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