Tiotropium Bromide hydrate (BA-679 BR hydrate) is a potent anticholinergic and bronchodilator, serving as a muscarinic receptor antagonist, specifically targeting mAChR. It is developed for treating chronic obstructive airways disease (COPD), demonstrating novel and long-lasting effects. Binding studies with [3H]tiotropium bromide in human lung reveal its high potency and equivalent affinity for M1-, M2-, and M3-receptors, making it roughly 10 times more effective than ipratropium bromide. It notably inhibits cholinergic nerve-induced contraction of both guinea-pig and human airways more potently than atropine or ipratropium bromide, albeit with a slower onset. Tiotropium bromide uniquely presents slow dissociation from M3-receptors on airway smooth muscle and rapid dissociation from M2 autoreceptors on cholinergic nerve terminals. As a quaternary ammonium derivative, it shows high affinity and special kinetic selectivity towards muscarinic receptors across M1-, M2-, and M3-subtypes, due to its slower dissociation from M1- and M3-receptors compared to M2-receptors.

Tiotropium bromide是一种强效的毒蕈碱受体拮抗剂，对M1-、M2-和M3-受体具有相同的亲和力，并且比ipratropium bromide强效约10倍。Tiotropium bromide对于通过胆碱能神经诱导的豚鼠和人类气道收缩具有强大的抑制作用，其起效比atropine或ipratropium bromide慢。Tiotropium bromide、ipratropium bromide和atropine在神经刺激下均可增加ACh的释放，这种效应对这三种拮抗剂来说同样迅速消退。Tiotropium bromide从M3-受体（位于气道平滑肌上）的解离速度慢，但从M2自身受体（位于胆碱能神经末梢上）的解离速度快。[1] Tiotropium显著抑制了AM、MonoMac6和A549细胞释放趋化性物质。[2] Tiotropium bromide抑制了来自PBMCs的Th2细胞因子的产生。[3]

Tiotropium bromide在急性和慢性哮喘小鼠模型中显著减少气道炎症和支气管肺泡灌洗液（BALF）中的Th2细胞因子产生。它显著降低哮喘小鼠模型中杯状细胞异型增生、气道平滑肌厚度以及气道纤维化。在慢性模型中，Tiotropium bromide还减少了BALF中TGF-beta1的水平。[3] Tiotropium抑制了过敏性哮喘持续状态的豚鼠模型中气道平滑肌质量增加、肌球蛋白表达和收缩性。[4] 在慢性阻塞性肺疾病（COPD）的豚鼠模型中，Tiotropium bromide消除了LPS诱导的中性粒细胞、杯状细胞增加、胶原沉积和肌化微血管的增加，但对肺气肿没有影响。[5]