High impact information on Rilmakalim

• HMR 1402 inhibited rilmakalim-induced currents in rat and guinea pig myocytes (IC(50) = 60 and 509 nM, respectively) [1].
• Mepacrine and proadifen inhibited Hoe-234-initiated relaxation in BCA and PCA, while econazole only inhibited Hoe 234-induced relaxation in PCA [2].
• The presence of urothelium did not affect the concentration-response curves for rilmakalim, with the exception of KCl-induced contractions in pig [3].
• In this study we examined whether intact urothelium may modulate the effect of the selective KATP channel opener rilmakalim [3].
• For rilmakalim and salbutamol, 60-130 times higher doses were needed for protection against histamine-induced bronchoconstriction in normoreactive guinea pigs than for reversal of airways hyperreactivity [4].

Biological context of Rilmakalim

• In action potential recordings, 0.1 microM rilmakalim was used [5].
• RESULTS: In control females, rilmakalim and diazoxide, but not pinacidil elicited concentration-dependent decrease of heart rate [6].
• Electrophysiological recordings of the membrane potential using the "perforated patch" method (n = 4), showed that rilmakalim (1 muM) induced hyperpolarization of capillaries towards the K+ equilibrium potential, confirming our fluorometric measurements [7].
• CONCLUSION: Our results indicate that estrogen downregulates H-LDH production and specifically modulate pinacidil action in guinea pig right atria, probably by changes of binding site for this drug in SUR2A receptor, but not for rilmakalim and diazoxide [6].
• In all species and independent of the route of administration Hoe 234 lowered systemic blood pressure accompanied with increases in heart rate [8].

Anatomical context of Rilmakalim

• On the contrary, the K+ channel activator Hoe 234 which elicits hyperpolarization of the endothelial cell membrane, augmented the sustained phase of the agonist-induced intracellular Ca2+ signal, but not the resting intracellular Ca2+ level [9].
• 6. In cardiac Purkinje fibers, tetraethylammonium (TEA; 20 mM) significantly reduced the effects of rilmakalim (2. 4 microM) on the APD [10].
• Pretreatment with phalloidin (20 microM), a cytoskeleton stabilizer, prevented an intensification of the effects of rilmakalim in hypotonic solution and returned R and Hill's coefficients to the control values [11].
• Differential antivasoconstrictor effects of levcromakalim and rilmakalim on the isolated human mammary artery and saphenous vein [12].

Associations of Rilmakalim with other chemical compounds

• The rilmakalim-induced shortening of the APD90 was half-maximally antagonized by glibenclamide and HMR 1883 with 10 nM and 0.4 microM, respectively (pHo = 6.5) [13].
• Adenosine triphosphate-dependent K currents activated by metabolic inhibition in rat ventricular myocytes differ from those elicited by the channel opener rilmakalim [14].
• 4. Stable early afterdepolarizations induced in Purkinje fibers by berberine (100 microM) were reversibly blocked by rilmakalim (2.4 microM), which also suppressed late afterdepolarizations induced in Purkinje fibers treated with ouabain (0.3-0.5 microM) [10].
• Levcromakalim induced a concentration-dependent and equipotent inhibition of contraction of HIMA and HSV preconstricted by EFS and exogenoulsy applied NA, while rilmakalim produced a stronger inhibition of EFS- than NA-evoked contractions [12].

Gene context of Rilmakalim

• In conclusion, after metabolic inhibition the amplitude of the activated KATP current is about twice as high as under saturating concentrations of the opener rilmakalim [14].
• They also suggest that the effect of rilmakalim on EFS-evoked contractions involves K(ATP) channels located pre-synaptically [12].

Analytical, diagnostic and therapeutic context of Rilmakalim

• 1. The effects of rilmakalim, a potassium channel opener, were studied on rabbit cardiac Purkinje, ventricular muscle and atrial fibers, with the use of conventional microelectrode techniques [10].

References