Wake Forest Institute for Regenerative Medicine, Wake Forest University Medical School, Medical Center Boulevard, Winston Salem, NC 27157, USA.
Eur Urol. 2011 Mar;59(3):377-86. doi: 10.1016/j.eururo.2010.11.040. Epub 2010 Dec 8.
Antimuscarinics are the drugs of choice for the treatment of detrusor overactivity (DO) and overactive bladder (OAB) syndrome. However, the mechanisms for their beneficial effects have not yet been definitely established.
Literature available on the pathophysiologic aspects of storage symptoms and of antimuscarinic actions on the bladder was reviewed.
Medline was searched for the period ending October 2010 and included studies on human and animal tissues and animal models. Clinical studies exploring mechanisms involved in the effects of antimuscarinics were included. Searches were limited to the English language.
Evidence for release of acetylcholine (ACh) from non-neuronal as well as neuronal sources during bladder filling has been demonstrated in isolated animal bladders as well as the human bladder. Urothelially derived ACh, probably via release of adenosine triphosphate, may stimulate afferent activity ("afferent noise") from the bladder contributing to OAB and DO. Afferent noise may also be generated by local ACh release within the detrusor muscle. This afferent activity can be inhibited by antimuscarinics at the low concentrations obtained with doses recommended for clinical use in OAB/DO. Within this therapeutic window, antimuscarinics may decrease OAB symptoms and DO without affecting the voiding contraction. Changes in muscarinic receptor functions have been demonstrated with aging and in different disorders associated with OAB/DO.
ACh, derived from non-neuronal as well as neuronal sources and during bladder filling, directly or indirectly stimulates afferent activity from the bladder, contributing to OAB and DO. By inhibiting this effect, antimuscarinics may decrease OAB symptoms and DO without affecting the voiding contraction. Even if changes in muscarinic receptor functions may occur with aging and in different disorders associated with OAB/DO, such changes have not been shown convincingly to modify the beneficial effect of antimuscarinics in OAB/DO.
抗毒蕈碱药物是治疗逼尿肌过度活动（DO）和膀胱过度活动症（OAB）的首选药物。然而，其有益效果的机制尚未得到明确确定。
综述了关于储存症状的病理生理方面和抗毒蕈碱药物对膀胱作用的文献。
搜索了截至 2010 年 10 月的 Medline，并包括了人类和动物组织以及动物模型的研究。纳入了探索抗毒蕈碱药物作用机制的临床研究。搜索仅限于英语。
已经在分离的动物膀胱以及人类膀胱中证明，在膀胱充盈过程中，非神经元和神经元来源都会释放乙酰胆碱（ACh）。尿路上皮衍生的 ACh 可能通过释放三磷酸腺苷刺激来自膀胱的传入活动（“传入噪声”），导致 OAB 和 DO。局部 ACh 释放也可在逼尿肌内产生传入噪声。这种传入活动可以被在推荐用于 OAB/DO 临床治疗的剂量下获得的低浓度的抗毒蕈碱药物抑制。在这个治疗窗内，抗毒蕈碱药物可能会减少 OAB 症状和 DO，而不会影响排尿收缩。已经证明，随着年龄的增长以及与 OAB/DO 相关的不同疾病，毒蕈碱受体功能会发生变化。
在膀胱充盈过程中，来自非神经元和神经元来源的 ACh 直接或间接刺激来自膀胱的传入活动，导致 OAB 和 DO。通过抑制这种作用，抗毒蕈碱药物可能会减少 OAB 症状和 DO，而不会影响排尿收缩。即使毒蕈碱受体功能的变化可能随着年龄的增长以及与 OAB/DO 相关的不同疾病而发生，这种变化也没有令人信服地证明会改变抗毒蕈碱药物在 OAB/DO 中的有益效果。
