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The effect of midodrine and its active metabolite ST 1059 on the human urethra in vitro and in vivo.

The directly acting alpha-receptor agonist midodrine is active through its metabolite ST 1059. The effects of ST 1059 were investigated in vitro on strips of human urethra and on small human omental arteries. ST 1059 was as potent as noradrenaline on the isolated urethra, but had only 40% of noradrenaline's maximum activity. In omental arteries noradrenaline was at least ten times more potent than ST 1059 which only had about one fourth of noradrenaline's maximum activity. Compared to its effect on the vessels ST 1059 was ten times more effective on the urethra, whereas noradrenaline was slightly more effective on the vessels than on the urethra. Thus, in vitro St 1059 exhibited some selectivity for urethral alpha-receptors. When midodrine was given to 13 female patients with stress incontinence in the doses 2.5 mg and 5 mg x 3 for two weeks, only two had a positive urethral closure pressure during treatment and were subjectively improved. There were no effects on blood pressure and heart rate; one patient complained of pilo-erection. Two further patients received 7.5 mg x 3 for two weeks; both were subjectively improved but complained of pronounced pilo-erection. Only one of them had a positive urethral closure pressure during treatment. Blood pressure or heart rate did not change. Although it cannot be excluded that midodrine can increase intraurethral pressure with minor effects on blood pressure, it seems as the doses needed cause pilo-erection to an extent that limits the clinical usefulness of the drug.