Department of Experimental and Clinical Medicine, Research Unit of Histology and Embryology, University of Florence, Viale Pieraccini, 650139 Florence, Italy.
Curr Pharm Des. 2018;24(16):1772-1779. doi: 10.2174/1381612824666180507122935.
Otilonium bromide (OB) is a drug with spasmolytic activity belonging to quaternary ammonium derivatives and extensively used to treat patients affected by the Irritable Bowel Syndrome (IBS). Thanks to its peculiar pharmacokinetic, OB concentrates in the large bowel wall and acts locally. From the pharmacodynamics point of view, OB is able to inhibit i) the main patterns of human colonic motility in vitro; ii) the contractility caused by excitatory motor neurons stimulation (pre-synaptic action) and iii) the contractility caused by the direct action of excitatory neurotransmitters (post-synaptic action). Interestingly, these effects derive from a complex interaction between the drug and several cellular targets. The main action consists in the blockade of Ca2+ entry through L-type Ca2+ channels and interference with intracytoplasmatic Ca2+ mobilization necessary for SMC contraction, thus preventing excessive bowel contractions and abdominal cramps. Further, OB blocks the T-type Ca2+ channels and interferes with the muscarinic responses; it interacts, directly or indirectly, with the tachykinin receptors on SMC and on primary afferent neurons whose combined effects may result in the reduction of motility and abdominal pain. In summary, a revision of this complex picture of OB activity could help to better address its therapeutic use.
奥替溴铵（OB）是一种具有解痉作用的药物，属于季铵衍生物，广泛用于治疗肠易激综合征（IBS）患者。由于其独特的药代动力学特性，OB 在大肠壁中浓缩并发挥局部作用。从药效学角度来看，OB 能够抑制：i）体外人类结肠运动的主要模式；ii）兴奋运动神经元刺激引起的收缩性（突触前作用）和 iii）兴奋神经递质的直接作用引起的收缩性（突触后作用）。有趣的是，这些作用源自药物与多个细胞靶标的复杂相互作用。其主要作用包括通过 L 型钙通道阻断 Ca2+内流，并干扰平滑肌收缩所需的细胞内 Ca2+动员，从而防止过度的肠道收缩和腹痛。此外，OB 还可阻断 T 型钙通道并干扰毒蕈碱反应；它直接或间接地与平滑肌和初级传入神经元上的速激肽受体相互作用，其综合作用可能导致运动和腹痛减少。综上所述，对 OB 活性的这一复杂情况进行审查有助于更好地解决其治疗用途。
