Abstract:Normal rats as well as rats with bladder hypertrophy secondary to outflow obstruction were investigated cystometrically before and after administration of the potassium channel openers pinacidil or cromakalim one mg./kg. orally. In normal rats cromakalim decreased micturition pressure by 15 +/- 6%. A diminished micturition pressure was also seen after pinacidil (by 18 +/- 8%) but this did not achieve statistical significance. Further, no clear-cut effects on bladder capacity, residual volume, basal bladder pre… Show more
“…Although this observation is consistent with the preclinical efficacy results in animal models (Malmgren et al, 1989), in the absence of placebo-controlled and definitive clinical data, it is thought that cromakalim and subsequent analogs lack sufficient bladder selectivity relative to the vascular effects. Consequently, further clinical proof of principle for KCOs for bladder overactivity mandates a compound with improved selectivity.…”
supporting
confidence: 73%
“…Urinary bladder smooth muscle, unlike arterial smooth muscle, exhibits action potentials and phasic myogenic activity. Previous studies have shown that KCOs can effectively suppress spontaneous contractions in human urinary bladder (Wammack et al, 1994), guinea pig bladder (Fujii et al, 1990;Hashitani et al, 1996), or hypertrophied rat bladder with instability (Malmgren et al, 1989). In the present study, a comparison of the IC 50 values to suppress spontaneous phasic activity showed that A-278637 is 5-to 10-fold more potent compared with both ZD6169 and WAY-133537.…”
“…Although this observation is consistent with the preclinical efficacy results in animal models (Malmgren et al, 1989), in the absence of placebo-controlled and definitive clinical data, it is thought that cromakalim and subsequent analogs lack sufficient bladder selectivity relative to the vascular effects. Consequently, further clinical proof of principle for KCOs for bladder overactivity mandates a compound with improved selectivity.…”
supporting
confidence: 73%
“…Urinary bladder smooth muscle, unlike arterial smooth muscle, exhibits action potentials and phasic myogenic activity. Previous studies have shown that KCOs can effectively suppress spontaneous contractions in human urinary bladder (Wammack et al, 1994), guinea pig bladder (Fujii et al, 1990;Hashitani et al, 1996), or hypertrophied rat bladder with instability (Malmgren et al, 1989). In the present study, a comparison of the IC 50 values to suppress spontaneous phasic activity showed that A-278637 is 5-to 10-fold more potent compared with both ZD6169 and WAY-133537.…”
“…They also depress contractions induced by electrical stimulation, carbachol, and low, but not high external K' concentrations (Anderson, 1993). The KC channel openers were particularly effective in hypertrophic rat bladder muscle in vitro (Malmgren et al 1990) and suppressed bladder hyperactivity in rats with bladder outflow obstruction without affecting bladder emptying (Malmgren et al 1989).…”
“…Cromakalim abolishes spontaneous bladder contractions in pigs [5], rats [8] and rabbits [9] with bladder instability, with little change in other urodynamic variables. Cromakalim also lowers blood pressure in pigs when administered in doses that suppress the unstable contractions [5].…”
The effects of the potassium channel opener levcromakalim (BRL 38227) 7.5 micrograms kg‐1 were examined on urodynamic variables and blood pressure during inflow and voiding cystometry in six high spinal cord lesion patients. Levcromakalim administration significantly increased the duration of bladder contraction (197 +/‐ 128 s to 267 +/‐ 167 s, P < 0.05) and also reduced blood pressure (126 +/‐ 13/67 +/‐ 9 mm Hg to 104 +/‐ 25/52 +/‐ 12 mm Hg) but was without effect on other urodynamic parameters. Because of concerns about hypotensive responses, further studies involving higher doses of levcromakalim should be considered only if the drug was administered intravesically.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.