Phosphodiesterase 1 and 5 (PDE1 and PDE5)

Phosphodiesterase 1 (PDE1) and Phosphodiesterase 5 (PDE5) are key enzymes in the phosphodiesterase superfamily that regulate cellular signaling by hydrolyzing cyclic nucleotides [4, 5]. PDE1 is a calcium/calmodulin-dependent enzyme that acts on both cAMP and cGMP, playing a significant role in the central nervous system and cardiovascular regulation [5, 16]. PDE5 is highly specific for cGMP and is a primary regulator of vascular smooth muscle tone, particularly in the pulmonary vasculature and the corpus cavernosum [6, 11]. Drugs targeting these enzymes, such as sildenafil and tadalafil for PDE5 or investigational agents like lenrispodun for PDE1, work by preventing the degradation of cyclic nucleotides, thereby enhancing downstream signaling pathways like the NO-cGMP-PKG axis [8, 10, 14]. This mechanism leads to therapeutic effects such as vasodilation, improved cognitive function, and neuroprotection [9, 12]. These targets are clinically relevant for treating conditions ranging from erectile dysfunction and pulmonary arterial hypertension to neurodegenerative diseases like Alzheimer's [3, 11, 16].

Other names

Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterasecGMP-specific 3',5'-cyclic phosphodiesterasePDE1PDE5Dual PDE1/5 target

Inhibition of cyclic nucleotide hydrolysis (cAMP and cGMP), leading to increased intracellular levels of these second messengers and subsequent activation of protein kinases (PKA and PKG) [4, 5, 10].