Nehra Ajay, Kulaksizoglu Haluk
Department of Urology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Curr Urol Rep. 2002 Dec;3(6):467-70. doi: 10.1007/s11934-002-0099-z.
Penile erection occurs in response to visual, olfactory, imaginative, and tactile stimuli initiated within the brain and/or on the periphery. Responses to these stimuli are mediated by efferent autonomic outflow originating in the sacral spinal cord and transmitted by the cavernosal and penile nerves. A number of neurotransmitters can play an integral role in corpus cavernosum smooth muscle relaxation, in part regulating penile erection through increased smooth muscle synthesis of the secondary messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). In addition to direct-acting agents, there are indirect-acting smooth muscle-relaxing agents. Phosphodiesterase (PDE) inhibitors such as sildenafil act indirectly and require sexual stimulation and endogenous nitric oxide production to activate the cGMP pathway effectively. In contrast, agents such as prostaglandin E(1) (PGE(1)) act directly on the trabecular smooth muscle, binding to specific e-prostanoid receptors and increasing cAMP synthesis. For this reason the direct-acting agents do not require sexual stimulation for efficacy. Combination pharmacotherapy has been used experimentally to treat erectile dysfunction for 25 years, using combinations of cAMP synthesis augmentors, smooth muscle relaxants and PDE inhibitors, and alpha-blockers administered via intracavernosal injection. The present era of oral pharmacotherapy treatment has resulted in significant awareness in the field of sexual dysfunction; however, a single agent may not be ideal to sustain penile rigidity, especially if comorbidities and severity of erectile dysfunction are accounted for. The rationale for and recent reports on combination therapy are presented in this review.
阴茎勃起是对大脑和/或外周引发的视觉、嗅觉、想象及触觉刺激的反应。对这些刺激的反应由起源于骶脊髓的传出自主神经流出介导，并通过海绵体神经和阴茎神经传递。许多神经递质在海绵体平滑肌松弛中可发挥重要作用，部分通过增加平滑肌中第二信使环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）的合成来调节阴茎勃起。除了直接作用药物外，还有间接作用的平滑肌松弛剂。磷酸二酯酶（PDE）抑制剂如西地那非起间接作用，需要性刺激和内源性一氧化氮产生才能有效激活cGMP途径。相比之下，前列腺素E（1）（PGE（1））等药物直接作用于小梁平滑肌，与特定的e-前列腺素受体结合并增加cAMP合成。因此，直接作用药物的疗效不需要性刺激。联合药物治疗已被实验性用于治疗勃起功能障碍25年，使用cAMP合成增强剂、平滑肌松弛剂和PDE抑制剂以及通过海绵体内注射给药的α阻滞剂的组合。当前口服药物治疗时代已在性功能障碍领域引起了广泛关注；然而，单一药物可能并非维持阴茎硬度的理想选择，尤其是考虑到勃起功能障碍的合并症和严重程度时。本综述介绍了联合治疗的原理及近期报告。
