[¹²⁵I]A-312110, a Novel High-Affinity 1,4-Dihydropyridine ATP-sensitive K⁺Channel Opener: Characterization and Pharmacology of Binding

Abstract

Although ATP-sensitive K ϩ channels continue to be explored for their therapeutic potential, developments in high-affinity radioligands to investigate native and recombinant K ATP channels have been less forthcoming. This study reports the identification and pharmacological characterization of a novel iodinated 1,4-dihydropyridine K ATP channel opener, [ 125

Role of potassium ion channels in detrusor smooth muscle function and dysfunction

“…They are activated when the intracellular ATP concentration is low and the ADP concentration is high, thus linking the cell’s metabolic state with its membrane excitability. The specific K ATP channel inhibitor, glibenclamide, 16,94,95 does not affect DSM excitability or contractility in the absence of K ATP channel stimulation, a finding that questions whether or not K ATP channels contribute to DSM resting membrane potential under normal physiological conditions; 12,26,93 however, pharmacological activation of K ATP channels causes membrane hyperpolarization, which closes the L-type Ca V channels, thereby reducing DSM contractility. 16 Various chemically unrelated compounds, known as K ATP channel openers (such as cromakalim, levcromakalim, pinacidil, diazoxide, ZD6169, P1075 and A-312110) activate DSM K ATP channels directly, causing decreased membrane excitability and contractility.…”

1,4-Dihydropyridine Scaffold in Medicinal Chemistry, The Story so Far And Perspectives (Part 1): Action in Ion Channels and GPCRs

“…14) and compounds related to 16-18 (Fig. 14) [131][132][133]. These compounds were the basis for different SAR studies aimed at clarifying the importance of the stereochemistry of these compounds, with particular emphasis on the role of the R/S configuration of the chiral centre of the 1,4-DHP ring.…”

Investigation of myorelaxant activity of 9-aryl-3,4,6,7-tetrahydroacridine-1,8-(2H,5H,9H,10H)-diones in isolated rabbit gastric fundus

“…It was shown that these KATP channels play critical roles in modulating physiological processes such as insulin secretion, leptin release, synaptic transmission, and excitability of cardiac, vascular, and nonvascular smooth muscle (Davis-Taber et al, 2003).…”

“…Calcium channel blockers having 1,4-dihydropyridine (DHP) structure which nifedipine is the prototype and their condensed analogs such as bicyclo (quinoline) and tricyclo (acridine) have vasodilator and antihypertensive effects (Ö zturk et al, 2008;Simsek et al, 2008Simsek et al, , 2004Saraç et al, 2002;Berkan et al, 2002;Carroll et al, 2004a, b;Ashworth et al, 2002). Some DHP derivatives have also potassium channel opener activity (Klöckner and Trieschmann, 1989;Davis-Taber, et al, 2003;Grissmer and Cahalan, 1989;Mannhold, 2004;Gopalakrishnan et al, 2003). Frank and coworkers synthesized 9-(3-nitrophenyl)-3,4,6,7-tetrahydroacridine-1,8-(2H,5H,9H,10H)-dione and showed its potassium channel opener activity (Frank et al 1993).…”