Phosphodiesterase inhibitor

A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE), therefore preventing the inactivation of the intracellular second messengers, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), by the respective PDE subtype(s).

• Non-selective phosphodiesterase inhibitors:

1. the minor stimulant caffeine,
2. the bronchodilator theophylline,
3. IBMX (3-isobutyl-1-methylxanthine): used as investigative tool in pharmacological research.

• PDE1-selective inhibitors:

1. Vinpocetine

• PDE2-selective inhibitors:

1. EHNA

• PDE3-selective inhibitors:

1. enoximone and milrinone: used clinically for short-term treatment of cardiac failure. Clinically these drugs mimic sympathetic stimulation and increase cardiac output.
   PDE3 is sometimes refered to as cGMP-inhibited phosphodiesterase.

• PDE4-selective inhibitors:

1. rolipram: used as investigative tool in pharmacological research

PDE4 is the major cAMP-metabolizing enzyme found in inflammatory and immune cells. PDE4 inhibitors have proven potential as anti-inflammatory drugs especially in airway diseases. They suppress the release of inflammatory signals, e.g., cytokines, and inhibit the production of reactive oxygen species. PDE4 inhibitors have a high therapeutic and commercial potential as non-steroidal disease controllers in inflammatory airway diseases such as asthma, COPD and rhinitis

• PDE5-selective inhibitors:

1. sildenafil, tadalafil and vardenafil: selectively inhibit (PDE5), which is cGMP-specific and responsible for the degradation of cGMP in the corpus cavernosum. These phosphodiesterase inhibitors are used as remedies for erectile dysfunction.