Stahl M M, Ekström B, Sparf B, Mattiasson A, Andersson K E
Department of Clinical Pharmacology, Lund University Hospital, Sweden.
Neurourol Urodyn. 1995;14(6):647-55. doi: 10.1002/nau.1930140606.
Tolterodine, a novel compound intended for treatment of urgency and urge incontinence, has been characterized as a potent muscarinic receptor antagonist in pharmacological in vitro and in vivo studies. In cats, tolerodine was shown to reduce bladder pressure at doses significantly lower than those affecting salivation. To predict clinical effectiveness, an open pilot study was performed in healthy male volunteers. Efficacy was measured by cystometry and by spontaneously reported effects after administration of a single oral dose of tolterodine, 6.4 mg, given as a water solution. Tolterodine had distinct inhibitory effects on urinary bladder function, both at 1 and 5 hours post-dose. At 1 hour, but not at 5 hours post-dose tolterodine also significantly reduced stimulated salvation. In addition to the objectively demonstrated changes in urodynamic parameters, most volunteers experienced voiding difficulties. No significant changes in blood pressure, heart rate, or near point of accommodation were registered. Tolterodine, in the dosage used, was both objectively and subjectively shown to exert a marked inhibitory effect on micturition in healthy subjects, and the data suggest a more pronounced effect on bladder function than on salivation.
托特罗定是一种用于治疗尿急和急迫性尿失禁的新型化合物，在体外和体内药理学研究中已被表征为一种强效毒蕈碱受体拮抗剂。在猫身上，已表明托特罗定在剂量显著低于影响唾液分泌的剂量时就能降低膀胱压力。为预测临床疗效，在健康男性志愿者中进行了一项开放性初步研究。通过膀胱测压法以及单次口服6.4毫克托特罗定水溶液后自发报告的效果来测量疗效。给药后1小时和5小时，托特罗定对膀胱功能均有明显的抑制作用。给药后1小时，而非5小时，托特罗定还显著降低了刺激唾液分泌。除了尿动力学参数有客观显示的变化外，大多数志愿者还经历了排尿困难。血压、心率或近点调节均未出现显著变化。所用剂量的托特罗定在客观和主观上均显示对健康受试者的排尿有显著抑制作用，并且数据表明其对膀胱功能的影响比对唾液分泌的影响更为显著。
