PDEHemmstoffe

PDEHemmstoffe, or phosphodiesterase inhibitors, are a class of drugs that block phosphodiesterase enzymes responsible for hydrolyzing the cyclic nucleotides cAMP and cGMP. By inhibiting these enzymes, they raise intracellular levels of cyclic nucleotides, thereby modulating signaling pathways in a variety of tissues. The human genome encodes eleven PDE families (PDE1–PDE11), each with distinct substrate preferences and tissue distribution. Inhibitors can be selective for a single family or act more broadly.

Therapeutically, PDEHemmstoffe are employed to treat several conditions. PDE5 inhibitors, such as sildenafil, tadalafil and vardenafil, are used for erectile dysfunction and, in some cases, pulmonary arterial hypertension. PDE4 inhibitors, including roflumilast and apremilast, target inflammatory and autoimmune diseases like COPD and psoriasis. PDE3 inhibitors, such as cilostazol and milrinone, influence cardiac function and vascular tone. Other PDEs, including PDE1, PDE2, PDE9 and PDE10, are targets of investigations in neuroscience and metabolic regulation.

Mechanistically, the outcome of PDE inhibition depends on the specific isoenzyme targeted, the tissue involved, and the relative balance of cAMP versus cGMP signaling. Selectivity is crucial to minimize adverse effects, which commonly include headaches, flushing, nausea, hypotension, and, for PDE4 inhibitors, mood or GI symptoms. Drug interactions with nitrates, antihypertensives, and other vasoactive agents are also considerations.

Beyond therapy, PDEHemmstoffe serve as tools in biomedical research to dissect cyclic nucleotide signaling and to probe the roles of different PDE isoforms in physiology and disease.