Sexual HealthEstablishedHuman trials

PDE5 Inhibitor Stack

Phosphodiesterase Type 5 Inhibitor Class

Overview

The PDE5 inhibitor class encompasses sildenafil tadalafil vardenafil and avanafil — a family of compounds that share the mechanism of inhibiting the PDE5 enzyme responsible for cGMP breakdown in vascular smooth muscle. This class represents the most clinically successful sexual health pharmacology in history with multiple FDA approvals and applications extending beyond erectile dysfunction into pulmonary hypertension heart failure muscle research and cancer biology. Understanding the class provides context for comparing individual agents and emerging peptide alternatives.

Mechanism of Action

All PDE5 inhibitors work by competitive inhibition of the PDE5 enzyme at its active site preventing the hydrolysis of cGMP. Their selectivity differences for PDE5 vs related PDE enzymes (PDE6 in retina PDE11 in testes and heart) explain class differences in side effects. Sildenafil has higher PDE6 affinity explaining visual side effects. Tadalafil has PDE11 activity explaining back pain and myalgia. The clinical differentiation between agents is primarily pharmacokinetic — onset duration and food interactions — rather than mechanistic. Emerging PDE5 research has revealed roles in cardiac muscle skeletal muscle cancer biology and neurological conditions that may expand therapeutic applications significantly beyond sexual dysfunction.

Dosage Information

Typical Dose

See individual agent entries

Frequency

See individual agent entries

Administration

Oral for all approved agents

Notes

Class overview entry. See Sildenafil or Tadalafil entries for specific dosing information.

Where does PDE5 Inhibitor Stack sit?

See how this peptide compares across all 111 peptides in our database.

Evidence Score

0.75

Clinical trials
1.0035%
Literature
0.8930%
Community
0.0020%
Completeness
0.8815%
8 RCTs3 clinical trials6 reviews

Potential Side Effects

Class effects: headache flushing dyspepsiaAbsolute contraindication with nitrates across entire classIndividual agent-specific effects vary — see specific entries

Community Experiences

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Quick Facts

Administration
Oral for all approved agents
Typical Dose
See individual agent entries
Frequency
See individual agent entries
References
0 curated + 45 from PubMed
Clinical Trials
48 registered
Evidence Score
0.7 / 100