No abstract

We compared the potency of a selective ureteral relaxant KUL-7211 (beta(2)/beta(3)-adrenoceptor agonist; (-)-2-[4-(2-{[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)phenyloxy]acetic acid) with those of various spasmolytics on contractions in isolated canine ureteral preparations. Drug effects were evaluated on the tonic contraction induced by KCl (80 mM) and on spontaneous, 1x10(-5) M phenylephrine-, and 1x10(-6) M PGF(2alpha)-induced rhythmic contractions in isolated canine ureteral preparations using a functional experimental technique. The potencies (pD(2) value) of the following drugs were compared: KUL-7211, tamsulosin (an alpha(1A/1D)-adrenoceptor antagonist), prazosin (an alpha(1)-adrenoceptor antagonist), verapamil (a Ca(2+)-channel blocker), butylscopolamine (a nonselective muscarinic antagonist), and papaverine (a phosphodiesterase inhibitor). The rank order of relaxing potencies against KCl-induced tonic contraction was KUL-7211 (6.60)>tamsulosin(5.90)>verapamil(5.70)>papaverine(4.88)>prazosin (4.54). The rank order of potencies for reductions in spontaneous rhythmic contractions was KUL-7211 (6.80)>verapamil(6.12)>papaverine(5.05). Conversely, high concentrations of the two alpha-adrenoceptor antagonists (tamsulosin and prazosin) and of butylscopolamine enhanced the spontaneous contractions, although at low concentrations (up to 1x10(-6) M) they had no significant effects. For suppression of spasmogen-induced rhythmic contractions, the rank order of potencies was, against phenylephrine-induced contractions: KUL-7211 (6.95)>tamsulosin(6.26)>prazosin(5.68)>verapamil(5.64)>papaverine (5.03), and against PGF(2alpha)-induced contractions: KUL-7211 (7.05)>verapamil(6.70)>papaverine (5.27). Our results suggest that in dogs, the beta(2)/beta(3)-adrenoceptor agonist KUL-7211 is the most efficacious ureteral relaxant among the spasmolytics tested against various contractions. Possibly, KUL-7211 might be useful for promoting stone passage and relieving ureteral colic in urolithiasis patients.

We compared the urethral and cardiovascular effects of silodosin (selective α 且 A − adrenoceptor antagonist) ， anovel medication for benign prostatic hyperplasia (BPH)， with those of tamsulosin (selective α iA ／orTD − adrenoceptor an − tagonist)and naftopidil (selectiveα 且D − adrenoceptor antagonist) ． We evaluated the effects of these three drugs on the in − crease in intraurethral pressure (IUP) induced by electrical stimulation of the hypogastric nerve in anesthetized dogs with spontaneous BPH ． All three drugs dose − dependently reduced both the increase in IUP and the mean blood pressure (MBP) ． The rank order of potencies was tamsulosin ＞ silodosin ＞naftopidil for the reductions in both IUP and MBP ． However ， the uroselectivity (EDI5 value for hypotensive effect ／ID50 value for reduction in IUP)of silodosin (uroselec − tivity， 19， 8)was about 21 and 4 times higher than that of tamsulosin (0． 939)and naf 〔 opidil (4． 94) ， respectively ． These data suggest that silodosin might be one of the most useful medieations for dysuria in BPH patients ． Key wor "s − silodosin (KMD − 3213) ；α 且 A ・ adrenoceptor ；benign prostatic hyperplasia ；intraurethral pressure

We compared the urethral and cardiovascular eŠects of silodosin (selective a 1A -adrenoceptor antagonist), a novel medication for benign prostatic hyperplasia (BPH), with those of tamsulosin (selective a 1A /a 1D -adrenoceptor antagonist) and naftopidil (selective a 1D -adrenoceptor antagonist). We evaluated the eŠects of these three drugs on the increase in intraurethral pressure (IUP) induced by electrical stimulation of the hypogastric nerve in anesthetized dogs with spontaneous BPH. All three drugs dose-dependently reduced both the increase in IUP and the mean blood pressure (MBP). The rank order of potencies was tamsulosin＞silodosin＞naftopidil for the reductions in both IUP and MBP. However, the uroselectivity (ED 15 value for hypotensive eŠect/ID 50 value for reduction in IUP) of silodosin (uroselectivity, 19.8) was about 21 and 4 times higher than that of tamsulosin (0.939) and naftopidil (4.94), respectively. These data suggest that silodosin might be one of the most useful medications for dysuria in BPH patients.