Component

Phosphodiesterase 6 family

Retinal phototransduction phosphodiesterase, the off-target used for the selectivity ratio.

7 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What acts on it

  1. Tadalafil showed 85-fold greater selectivity against PDE6 than sildenafil.

    Tadalafil → Phosphodiesterase 6 family source_derived_draftungraded
    Experimental context and source evidence
    duration
    Not applicable
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    Isolated phosphodiesterase enzyme assays
    exposure
    Tadalafil compared with sildenafil
    limitations
    A ratio measured in enzyme assays; PDE6 is the retinal phototransduction phosphodiesterase, and this comparison does not by itself establish a difference in visual effects in people.
    organism
    Isolated phosphodiesterase enzyme assays
    plain_language
    Tadalafil showed 85-fold greater selectivity against PDE6 than sildenafil.
    primary_references
    The discovery of tadalafil: a novel and highly selective PDE5 inhibitor. 2. (2003). https://pubmed.ncbi.nlm.nih.gov/14521415/ DOI: 10.1021/jm0300577
    route
    In vitro
    tissue
    Selectivity ratio between PDE5 and PDE6

    Tadalafil: PDE5 occupancy, the cGMP route and three measured endpoints (2026-09-22) · lines 24–33

    Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata. Two references carry an unresolvable erratum and are recorded as corrected. Study-specific doses, effect sizes and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

    ## tadalafil-pde6-selectivity-versus-sildenafil Tadalafil showed 85-fold greater selectivity against PDE6 than sildenafil. Model/species: Isolated phosphodiesterase enzyme assays Tissue/system: Selectivity ratio between PDE5 and PDE6 Exposure: Tadalafil compared with sildenafil Route: In vitro Duration: Not applicable Limits: A ratio measured in enzyme assays; PDE6 is the retinal phototransduction phosphodiesterase, and this comparison does not by itself establish a difference in visual effects in people. Primary reference: The discovery of tadalafil: a novel and highly selective PDE5 inhibitor. 2. (2003). https://pubmed.ncbi.nlm.nih.gov/14521415/ DOI: 10.1021/jm0300577 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. The newly cloned phosphodiesterase PDE9A1 is highly specific for cyclic GMP with a Michaelis constant of approximately 0.07 micromolar, the lowest yet reported for a phosphodiesterase and at least 40 to 170 times lower than that of PDE5 and PDE6 respectively, it shows highest messenger RNA expression in kidney with lower levels in liver, lung and brain, and when expressed in COS-7 cells its activity was not inhibited well by either the nonselective inhibitor 3-isobutyl-1-methylxanthine or the new selective PDE5 inhibitor sildenafil, while the PDE1 and PDE5 inhibitor SCH51866 inhibited it with a half-maximal concentration of 1.55 micromolar.

    Sildenafil → Phosphodiesterase 9A source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/sildenafil-research/9624145.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ea6afcfbb102bf5a407894b06969c9fe245261fa8a1fea8fb92b201d8b24ace2", "start_char": 0, "end_char": 1265, "text_sha256": "ea6afcfbb102bf5a407894b06969c9fe245261fa8a1fea8fb92b201d8b24ace2"}
    experimental_model
    Cloning, expression and kinetic characterisation of a newly identified cyclic nucleotide phosphodiesterase family
    exposure
    Recombinant PDE9A1 against 3-isobutyl-1-methylxanthine, sildenafil and SCH51866
    limitations
    A cloning and characterisation report. The expression survey is messenger RNA rather than protein, and the enzyme is heterologously expressed.
    nutrient_topic
    Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. · Sildenafil
    organism
    Mouse
    plain_language
    There is another enzyme that destroys the same messenger even more avidly, and this drug does not touch it.
    primary_references
    [sil-p9624145] Identification and characterization of a novel family of cyclic nucleotide phosphodiesterases. (1998). https://pubmed.ncbi.nlm.nih.gov/9624145/ DOI: 10.1074/jbc.273.25.15553
    tissue_or_cell_type
    Kidney, liver, lung and brain messenger RNA

    Sildenafil: the enzyme it occupies instead of the substrate, why it cannot start a signal it can only preserve, the organic nitrate interaction that follows from that, the homologous retinal enzyme ten-fold away, and the pulmonary circulation where the same mechanism became a second indication (2026-09-22) · lines 236–247

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloning, expression and kinetic characterisation of a newly identified cyclic nucleotide phosphodiesterase family · source_derived_draft · unverified_draft

    ### sil-another-cgmp-enzyme-it-misses The newly cloned phosphodiesterase PDE9A1 is highly specific for cyclic GMP with a Michaelis constant of approximately 0.07 micromolar, the lowest yet reported for a phosphodiesterase and at least 40 to 170 times lower than that of PDE5 and PDE6 respectively, it shows highest messenger RNA expression in kidney with lower levels in liver, lung and brain, and when expressed in COS-7 cells its activity was not inhibited well by either the nonselective inhibitor 3-isobutyl-1-methylxanthine or the new selective PDE5 inhibitor sildenafil, while the PDE1 and PDE5 inhibitor SCH51866 inhibited it with a half-maximal concentration of 1.55 micromolar. Condition category: normal nutrient_topic: Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. plain_language: There is another enzyme that destroys the same messenger even more avidly, and this drug does not touch it. organism: Mouse tissue_or_cell_type: Kidney, liver, lung and brain messenger RNA experimental_model: Cloning, expression and kinetic characterisation of a newly identified cyclic nucleotide phosphodiesterase family limitations: A cloning and characterisation report. The expression survey is messenger RNA rather than protein, and the enzyme is heterologously expressed. exposure: Recombinant PDE9A1 against 3-isobutyl-1-methylxanthine, sildenafil and SCH51866 evidence_span: {"source_cache": "artifacts/sildenafil-research/9624145.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ea6afcfbb102bf5a407894b06969c9fe245261fa8a1fea8fb92b201d8b24ace2", "start_char": 0, "end_char": 1265, "text_sha256": "ea6afcfbb102bf5a407894b06969c9fe245261fa8a1fea8fb92b201d8b24ace2"} [sil-p9624145] Identification and characterization of a novel family of cyclic nucleotide phosphodiesterases. (1998). https://pubmed.ncbi.nlm.nih.gov/9624145/ DOI: 10.1074/jbc.273.25.15553
    Complete structured claim and evidence
  2. Sildenafil is a potent competitive inhibitor of PDE5 with a half-maximal inhibitory concentration of 3.5 nanomolar, selective over PDE1 to PDE4 by 80 to 19,000-fold and over retinal PDE6 by 10-fold, it enhanced cyclic GMP accumulation driven with sodium nitroprusside in rabbit corpus cavernosum without affecting cyclic AMP, and in the absence of nitric oxide drive it had no functional effect on human and rabbit isolated corpus cavernosum but potently potentiated the relaxant effects of nitric oxide on these tissues.

    Experimental context and source evidence
    availability_state
    biomarker_context Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/sildenafil-research/10629850.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "af056c516b44e35eac7b0511ba3a8403ed84c347af6094ebc153f68c8ee7db92", "start_char": 0, "end_char": 2057, "text_sha256": "af056c516b44e35eac7b0511ba3a8403ed84c347af6094ebc153f68c8ee7db92"}
    experimental_model
    Enzyme selectivity panel with isolated tissue, anaesthetised dog haemodynamics and isolated retina
    exposure
    Sildenafil with and without nitric oxide drive, and against glyceryl trinitrate, sodium nitroprusside and milrinone
    limitations
    The single most complete pharmacological characterisation here, covering the target, the absence of effect without upstream drive, the nitrate potentiation, the absence of an inotropic effect, and the retinal effect in one series.
    nutrient_topic
    Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. · Sildenafil
    organism
    Human, rabbit and dog
    plain_language
    With no signal present the drug does nothing; its entire action is to keep an existing signal from being cleared.
    primary_references
    [sil-p10629850] The pharmacology of sildenafil, a novel and selective inhibitor of phosphodiesterase (PDE) type 5. (1999). https://pubmed.ncbi.nlm.nih.gov/10629850/ DOI: 10.1254/fpj.114.supplement_22
    tissue_or_cell_type
    Corpus cavernosum, aorta, cardiac trabeculae and retina
    trigger_kind
    biomarker_context Imported condition classification; unverified.

    Sildenafil: the enzyme it occupies instead of the substrate, why it cannot start a signal it can only preserve, the organic nitrate interaction that follows from that, the homologous retinal enzyme ten-fold away, and the pulmonary circulation where the same mechanism became a second indication (2026-09-22) · lines 262–273

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme selectivity panel with isolated tissue, anaesthetised dog haemodynamics and isolated retina · source_derived_draft · unverified_draft

    ### sil-no-effect-without-nitric-oxide Sildenafil is a potent competitive inhibitor of PDE5 with a half-maximal inhibitory concentration of 3.5 nanomolar, selective over PDE1 to PDE4 by 80 to 19,000-fold and over retinal PDE6 by 10-fold, it enhanced cyclic GMP accumulation driven with sodium nitroprusside in rabbit corpus cavernosum without affecting cyclic AMP, and in the absence of nitric oxide drive it had no functional effect on human and rabbit isolated corpus cavernosum but potently potentiated the relaxant effects of nitric oxide on these tissues. Condition category: biomarker_context nutrient_topic: Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. plain_language: With no signal present the drug does nothing; its entire action is to keep an existing signal from being cleared. organism: Human, rabbit and dog tissue_or_cell_type: Corpus cavernosum, aorta, cardiac trabeculae and retina experimental_model: Enzyme selectivity panel with isolated tissue, anaesthetised dog haemodynamics and isolated retina limitations: The single most complete pharmacological characterisation here, covering the target, the absence of effect without upstream drive, the nitrate potentiation, the absence of an inotropic effect, and the retinal effect in one series. exposure: Sildenafil with and without nitric oxide drive, and against glyceryl trinitrate, sodium nitroprusside and milrinone evidence_span: {"source_cache": "artifacts/sildenafil-research/10629850.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "af056c516b44e35eac7b0511ba3a8403ed84c347af6094ebc153f68c8ee7db92", "start_char": 0, "end_char": 2057, "text_sha256": "af056c516b44e35eac7b0511ba3a8403ed84c347af6094ebc153f68c8ee7db92"} [sil-p10629850] The pharmacology of sildenafil, a novel and selective inhibitor of phosphodiesterase (PDE) type 5. (1999). https://pubmed.ncbi.nlm.nih.gov/10629850/ DOI: 10.1254/fpj.114.supplement_22
    Complete structured claim and evidence
  3. As a consequence of inhibition of PDE6 in the retina, sildenafil at 1 to 100 micromolar altered the kinetics of the light response of the isolated dog retina and in the anaesthetised dog modified the a-wave and b-wave of the electroretinogram induced by a flash of blue light, effects proportional to plasma concentrations, fully reversible, and occurring only following plasma concentrations approximately 30-fold higher than those active on intracavernosal pressure.

    Sildenafil → The electroretinogram a-wave and b-wave source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/sildenafil-research/10629850.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "af056c516b44e35eac7b0511ba3a8403ed84c347af6094ebc153f68c8ee7db92", "start_char": 0, "end_char": 2057, "text_sha256": "af056c516b44e35eac7b0511ba3a8403ed84c347af6094ebc153f68c8ee7db92"}
    experimental_model
    Enzyme selectivity panel with isolated tissue, anaesthetised dog haemodynamics and isolated retina
    exposure
    Sildenafil with and without nitric oxide drive, and against glyceryl trinitrate, sodium nitroprusside and milrinone
    limitations
    The single most complete pharmacological characterisation here, covering the target, the absence of effect without upstream drive, the nitrate potentiation, the absence of an inotropic effect, and the retinal effect in one series.
    nutrient_topic
    Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. · Sildenafil
    organism
    Human, rabbit and dog
    plain_language
    The retinal enzyme is reached too, reversibly, but only at concentrations about thirty times the useful one.
    primary_references
    [sil-p10629850] The pharmacology of sildenafil, a novel and selective inhibitor of phosphodiesterase (PDE) type 5. (1999). https://pubmed.ncbi.nlm.nih.gov/10629850/ DOI: 10.1254/fpj.114.supplement_22
    tissue_or_cell_type
    Corpus cavernosum, aorta, cardiac trabeculae and retina

    Sildenafil: the enzyme it occupies instead of the substrate, why it cannot start a signal it can only preserve, the organic nitrate interaction that follows from that, the homologous retinal enzyme ten-fold away, and the pulmonary circulation where the same mechanism became a second indication (2026-09-22) · lines 288–299

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme selectivity panel with isolated tissue, anaesthetised dog haemodynamics and isolated retina · source_derived_draft · unverified_draft

    ### sil-retinal-effect-at-thirty-fold As a consequence of inhibition of PDE6 in the retina, sildenafil at 1 to 100 micromolar altered the kinetics of the light response of the isolated dog retina and in the anaesthetised dog modified the a-wave and b-wave of the electroretinogram induced by a flash of blue light, effects proportional to plasma concentrations, fully reversible, and occurring only following plasma concentrations approximately 30-fold higher than those active on intracavernosal pressure. Condition category: normal nutrient_topic: Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. plain_language: The retinal enzyme is reached too, reversibly, but only at concentrations about thirty times the useful one. organism: Human, rabbit and dog tissue_or_cell_type: Corpus cavernosum, aorta, cardiac trabeculae and retina experimental_model: Enzyme selectivity panel with isolated tissue, anaesthetised dog haemodynamics and isolated retina limitations: The single most complete pharmacological characterisation here, covering the target, the absence of effect without upstream drive, the nitrate potentiation, the absence of an inotropic effect, and the retinal effect in one series. exposure: Sildenafil with and without nitric oxide drive, and against glyceryl trinitrate, sodium nitroprusside and milrinone evidence_span: {"source_cache": "artifacts/sildenafil-research/10629850.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "af056c516b44e35eac7b0511ba3a8403ed84c347af6094ebc153f68c8ee7db92", "start_char": 0, "end_char": 2057, "text_sha256": "af056c516b44e35eac7b0511ba3a8403ed84c347af6094ebc153f68c8ee7db92"} [sil-p10629850] The pharmacology of sildenafil, a novel and selective inhibitor of phosphodiesterase (PDE) type 5. (1999). https://pubmed.ncbi.nlm.nih.gov/10629850/ DOI: 10.1254/fpj.114.supplement_22
    Complete structured claim and evidence
  4. Early in development it was noted that besides its major inhibitory effect on the intended target, the vascular-associated PDE5, the drug also exerts a lesser but definite inhibitory effect on the closely related PDE6 located in the retina, and for this reason preclinical evaluation included electroretinography plus postmortem histology and an extended eye examination was incorporated into clinical protocols, with data on the incidence, duration and type of colour vision defects observed at different doses.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/sildenafil-research/10703120.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fc004205f7e036cf52e469c5f9941c4f69d216a012ccd8a588052b950c1077e6", "start_char": 0, "end_char": 2146, "text_sha256": "fc004205f7e036cf52e469c5f9941c4f69d216a012ccd8a588052b950c1077e6"}
    experimental_model
    Review of how the ocular safety profile was established from preclinical work through to post-marketing surveillance
    exposure
    Electroretinography and histology in preclinical evaluation, with extended eye examination in clinical protocols and registry surveillance
    limitations
    A methodological review of how the signal was tracked rather than a new measurement. It is useful because it records that the retinal effect was predicted before it was looked for.
    nutrient_topic
    Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. · Sildenafil
    organism
    Human and animal
    plain_language
    The visual effect was not a surprise; the homology between the two enzymes predicted it and the trials were designed to look for it.
    primary_references
    [sil-p10703120] Ocular safety of Viagra, (sildenafil citrate). (1999). https://pubmed.ncbi.nlm.nih.gov/10703120/
    tissue_or_cell_type
    Retina

    Sildenafil: the enzyme it occupies instead of the substrate, why it cannot start a signal it can only preserve, the organic nitrate interaction that follows from that, the homologous retinal enzyme ten-fold away, and the pulmonary circulation where the same mechanism became a second indication (2026-09-22) · lines 496–507

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of how the ocular safety profile was established from preclinical work through to post-marketing surveillance · source_derived_draft · unverified_draft

    ### sil-the-off-target-was-predicted Early in development it was noted that besides its major inhibitory effect on the intended target, the vascular-associated PDE5, the drug also exerts a lesser but definite inhibitory effect on the closely related PDE6 located in the retina, and for this reason preclinical evaluation included electroretinography plus postmortem histology and an extended eye examination was incorporated into clinical protocols, with data on the incidence, duration and type of colour vision defects observed at different doses. Condition category: normal nutrient_topic: Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. plain_language: The visual effect was not a surprise; the homology between the two enzymes predicted it and the trials were designed to look for it. organism: Human and animal tissue_or_cell_type: Retina experimental_model: Review of how the ocular safety profile was established from preclinical work through to post-marketing surveillance limitations: A methodological review of how the signal was tracked rather than a new measurement. It is useful because it records that the retinal effect was predicted before it was looked for. exposure: Electroretinography and histology in preclinical evaluation, with extended eye examination in clinical protocols and registry surveillance evidence_span: {"source_cache": "artifacts/sildenafil-research/10703120.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fc004205f7e036cf52e469c5f9941c4f69d216a012ccd8a588052b950c1077e6", "start_char": 0, "end_char": 2146, "text_sha256": "fc004205f7e036cf52e469c5f9941c4f69d216a012ccd8a588052b950c1077e6"} [sil-p10703120] Ocular safety of Viagra, (sildenafil citrate). (1999). https://pubmed.ncbi.nlm.nih.gov/10703120/
    Complete structured claim and evidence
  5. Sildenafil inhibited PDE5 from human corpus cavernosum with a geometric mean half-maximal inhibitory concentration of 3.5 nanomolar and was approximately 240-fold more potent than zaprinast, values for inhibition of PDE1 to PDE4 were 80 to more than 8500 times greater than that for PDE5, and the value for PDE6 at 33 nanomolar was approximately 9-fold greater.

    Sildenafil → Phosphodiesterase 5 family source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/sildenafil-research/9598563.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "860e09237bbae4ec5bb65a640186902908ccb9c6ec502b504a1ecddbb33810a2", "start_char": 0, "end_char": 1755, "text_sha256": "860e09237bbae4ec5bb65a640186902908ccb9c6ec502b504a1ecddbb33810a2"}
    experimental_model
    Isolated human corpus cavernosum strips with electrical field stimulation, and phosphodiesterase assays across families 1 to 6
    exposure
    Sildenafil against PDE1 to PDE5 prepared from human tissues and PDE6 from bovine retina, with zaprinast as comparator
    limitations
    Measures the full selectivity series in one laboratory using the same method, which is what makes the ratios comparable. The PDE6 preparation is bovine retina rather than human.
    nutrient_topic
    Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. · Sildenafil
    organism
    Human and bovine enzyme
    plain_language
    It is hundreds to thousands of times more selective against most of the enzyme family, and only about nine times against the one in the retina.
    primary_references
    [sil-p9598563] Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. (1998). https://pubmed.ncbi.nlm.nih.gov/9598563/ DOI: 10.1016/s0022-5347(01)63299-3
    tissue_or_cell_type
    Corpus cavernosum and bovine retina

    Sildenafil: the enzyme it occupies instead of the substrate, why it cannot start a signal it can only preserve, the organic nitrate interaction that follows from that, the homologous retinal enzyme ten-fold away, and the pulmonary circulation where the same mechanism became a second indication (2026-09-22) · lines 132–143

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated human corpus cavernosum strips with electrical field stimulation, and phosphodiesterase assays across families 1 to 6 · source_derived_draft · unverified_draft

    ### sil-the-selectivity-series Sildenafil inhibited PDE5 from human corpus cavernosum with a geometric mean half-maximal inhibitory concentration of 3.5 nanomolar and was approximately 240-fold more potent than zaprinast, values for inhibition of PDE1 to PDE4 were 80 to more than 8500 times greater than that for PDE5, and the value for PDE6 at 33 nanomolar was approximately 9-fold greater. Condition category: normal nutrient_topic: Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. plain_language: It is hundreds to thousands of times more selective against most of the enzyme family, and only about nine times against the one in the retina. organism: Human and bovine enzyme tissue_or_cell_type: Corpus cavernosum and bovine retina experimental_model: Isolated human corpus cavernosum strips with electrical field stimulation, and phosphodiesterase assays across families 1 to 6 limitations: Measures the full selectivity series in one laboratory using the same method, which is what makes the ratios comparable. The PDE6 preparation is bovine retina rather than human. exposure: Sildenafil against PDE1 to PDE5 prepared from human tissues and PDE6 from bovine retina, with zaprinast as comparator evidence_span: {"source_cache": "artifacts/sildenafil-research/9598563.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "860e09237bbae4ec5bb65a640186902908ccb9c6ec502b504a1ecddbb33810a2", "start_char": 0, "end_char": 1755, "text_sha256": "860e09237bbae4ec5bb65a640186902908ccb9c6ec502b504a1ecddbb33810a2"} [sil-p9598563] Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. (1998). https://pubmed.ncbi.nlm.nih.gov/9598563/ DOI: 10.1016/s0022-5347(01)63299-3
    Complete structured claim and evidence
  6. Sildenafil has a mild inhibitory effect on PDE6, which controls the level of cyclic guanosine monophosphate in the retina, and it may cause a perception of bluish haze or increased light sensitivity in some patients, with long-term retinal damage not reported although long-term electroretinographic studies have not been performed; the drug causes a mild lowering of blood pressure and is contraindicated in patients taking any form of nitrate medication.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/sildenafil-research/10541153.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8c5d3c6e9d606690e6cc997086ded515a4e9f785561a7fc58fdbfb75b3f0a79a", "start_char": 0, "end_char": 1024, "text_sha256": "8c5d3c6e9d606690e6cc997086ded515a4e9f785561a7fc58fdbfb75b3f0a79a"}
    experimental_model
    Review of the ophthalmic profile shortly after marketing approval
    exposure
    Reported visual effects at therapeutic doses
    limitations
    A short review written in the first year of marketing. It records explicitly that long-term electroretinographic studies had not been performed, which is the limitation that matters for the claim.
    nutrient_topic
    Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. · Sildenafil
    organism
    Human
    plain_language
    The colour disturbance some people notice is the same drug reaching the retinal version of the enzyme.
    primary_references
    [sil-p10541153] Sildenafil (Viagra) and ophthalmology. (1999). https://pubmed.ncbi.nlm.nih.gov/10541153/ DOI: 10.1016/s0039-6257(99)00079-x
    tissue_or_cell_type
    Retina

    Sildenafil: the enzyme it occupies instead of the substrate, why it cannot start a signal it can only preserve, the organic nitrate interaction that follows from that, the homologous retinal enzyme ten-fold away, and the pulmonary circulation where the same mechanism became a second indication (2026-09-22) · lines 483–494

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of the ophthalmic profile shortly after marketing approval · source_derived_draft · unverified_draft

    ### sil-transient-visual-disturbance Sildenafil has a mild inhibitory effect on PDE6, which controls the level of cyclic guanosine monophosphate in the retina, and it may cause a perception of bluish haze or increased light sensitivity in some patients, with long-term retinal damage not reported although long-term electroretinographic studies have not been performed; the drug causes a mild lowering of blood pressure and is contraindicated in patients taking any form of nitrate medication. Condition category: normal nutrient_topic: Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. plain_language: The colour disturbance some people notice is the same drug reaching the retinal version of the enzyme. organism: Human tissue_or_cell_type: Retina experimental_model: Review of the ophthalmic profile shortly after marketing approval limitations: A short review written in the first year of marketing. It records explicitly that long-term electroretinographic studies had not been performed, which is the limitation that matters for the claim. exposure: Reported visual effects at therapeutic doses evidence_span: {"source_cache": "artifacts/sildenafil-research/10541153.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8c5d3c6e9d606690e6cc997086ded515a4e9f785561a7fc58fdbfb75b3f0a79a", "start_char": 0, "end_char": 1024, "text_sha256": "8c5d3c6e9d606690e6cc997086ded515a4e9f785561a7fc58fdbfb75b3f0a79a"} [sil-p10541153] Sildenafil (Viagra) and ophthalmology. (1999). https://pubmed.ncbi.nlm.nih.gov/10541153/ DOI: 10.1016/s0039-6257(99)00079-x
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