Drugs that increase cyclic GMP (cGMP) primarily do so by either stimulating its production or inhibiting its degradation. The most well-known examples achieve this through inhibition of phosphodiesterase type 5 (PDE5).
Here's a breakdown:
PDE5 Inhibitors
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Mechanism: These drugs inhibit PDE5, an enzyme that breaks down cGMP. By preventing cGMP breakdown, they effectively increase cGMP levels in certain tissues.
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Examples:
- Sildenafil (Viagra): Primarily used for erectile dysfunction.
- Tadalafil (Cialis): Used for erectile dysfunction and benign prostatic hyperplasia (BPH).
- Vardenafil (Levitra): Used for erectile dysfunction.
- Avanafil (Stendra): Another PDE5 inhibitor for erectile dysfunction.
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Effects: Increased cGMP leads to activation of protein kinase G (PKG), which results in vasodilation, particularly in the penile vessels, facilitating erection. They can also lower pulmonary arterial pressure and are used for pulmonary hypertension.
Other mechanisms:
While PDE5 inhibitors are the most common drugs that increase cGMP, other mechanisms exist:
- Guanylate cyclase stimulators: These drugs directly stimulate the production of cGMP by activating guanylate cyclase, the enzyme that synthesizes cGMP from GTP (guanosine triphosphate). An example of this type of drug is Riociguat, used to treat pulmonary hypertension.
Summary Table:
| Drug Class | Mechanism of Action | Examples | Primary Use |
|---|---|---|---|
| PDE5 Inhibitors | Inhibits cGMP breakdown | Sildenafil, Tadalafil, Vardenafil, Avanafil | Erectile Dysfunction, Pulmonary Hypertension |
| Guanylate Cyclase Stimulators | Stimulates cGMP production | Riociguat | Pulmonary Hypertension |
In essence, drugs increasing cGMP either prevent its breakdown or stimulate its production, influencing various physiological processes, most notably vasodilation.
