Bischoff E
Bayer Pharma Research, Bayer Healthcare Wuppertal, PH-R-EU-CV-ll, Wuppertal, Germany.
Int J Impot Res. 2004 Jun;16 Suppl 1:S11-4. doi: 10.1038/sj.ijir.3901208.
Phosphodiesterases (PDEs) play a decisive role in cyclic nucleotide-mediated intracellular signaling. As PDEs are expressed in a variety of tissues, selectivity is a prerequisite for a therapeutically applicable PDE inhibitor. Sildenafil, vardenafil, and tadalafil are selective for PDE5, with vardenafil exhibiting the highest potency and minimal inhibition of other PDEs, with the exception of PDE6. Tadalafil is extremely selective for PDE5, but also potently inhibits PDE11, an enzyme with unknown physiological function. As PDE1 is expressed in the brain, myocardium, and vascular smooth muscle cells, nonselectivity with respect to this enzyme (selectivity: tadalafil>vardenafil>sildenafil) may result in vasodilation and tachycardia. Inhibition of PDE6 (selectivity: tadalafil>vardenafil congruent with sildenafil), which is expressed only in retina and functions in visual transduction, can transiently disturb vision. PDE5 inhibitors may also indirectly inhibit PDE3 by increasing cyclic guanosine monophospate levels, thereby elevating heart rate and vasodilation while inhibiting platelet aggregation.
磷酸二酯酶（PDEs）在环核苷酸介导的细胞内信号传导中起决定性作用。由于PDEs在多种组织中表达，因此选择性是治疗用PDE抑制剂的先决条件。西地那非、伐地那非和他达拉非对PDE5具有选择性，其中伐地那非效力最高，对其他PDEs（PDE6除外）的抑制作用最小。他达拉非对PDE5具有极高的选择性，但也能有效抑制PDE11，这是一种生理功能未知的酶。由于PDE1在脑、心肌和血管平滑肌细胞中表达，对该酶的非选择性（选择性：他达拉非>伐地那非>西地那非）可能导致血管舒张和心动过速。仅在视网膜中表达并在视觉转导中起作用的PDE6的抑制作用（选择性：他达拉非>伐地那非与西地那非相当）可暂时干扰视力。PDE5抑制剂还可能通过增加环磷酸鸟苷水平间接抑制PDE3，从而在抑制血小板聚集的同时提高心率和血管舒张。
