The effect of levcromakalim (BRL 38227) on bladder function in patients with high spinal cord lesions.

Abstract

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.

Suppression of human detrusor smooth muscle excitability and contractility via pharmacological activation of large conductance Ca2+-activated K+ channels

“…Because the BK channels appear to be restricted to DSM cells with no detectable expression in nerves or other components of the detrusor (42), the effects of NS-1619 seen in this study are due to a direct effect of this compound on the DSM BK channels. Prior clinical studies investigating nonselective openers of the ATP-sensitive K ϩ channels for the treatment of bladder dysfunction have demonstrated considerable effects on blood pressure at doses that have negligible effects on bladder tissue (14,22). However, such studies have not utilized BK channelspecific agents.…”

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

“…In clinical trials performed with the first generation of K ϩ channel openers, no bladder effects have been found at oral doses already lowering blood pressure Komersova et al, 1995). No other K ϩ channel opener seems to have passed the proof of concept stage, and there is at present no convincing evidence showing that K ϩ channel opening is a useful principle for treatment of detrusor overactivity .…”

BL-1249 [(5,6,7,8-Tetrahydro-naphthalen-1-yl)-[2-(1H-tetrazol-5-yl)-phenyl]-amine]: A Putative Potassium Channel Opener with Bladder-Relaxant Properties

“…Unfortunately, however, reported K ATP channel openers exhibited only partial or no bladder selectivity either in vitro or in vivo (Edwards et al, 1991;Chess-Williams et al, 1999;Wojdan et al, 1999;Brune et al, 2002;Fabiyi et al, 2003). To date, K ATP channel openers have not proven to be clinically effective, due in part to cardiovascular side effects (Komersova et al, 1995), casting doubt on whether true bladder selectivity can be achieved by targeting K ATP channels.…”