RS 30026: a potent and effective calcium channel agonist

Abstract

1 A series of dihydropyridine derivatives has been evaluated for calcium channel agonist activity using reversal of nisoldipine-induced inhibition of beating of aggregates of embryonic chick myocytes. This test appears to be specific for calcium channel agonists since isoprenaline and cardiac glycosides are inactive. 2 RS 30026 was the most potent of the series, was significantly more potent than CGP 28392 and of similar potency to Bay K 8644 (pEC50 = 7.45, 6.16 and 7.20, respectively 6 RS 30026 appears to be the most potent and effective calcium channel agonist described to date.

Quercetin as a novel activator of L‐type Ca2+channels in rat tail artery smooth muscle cells

“…Naturally occurring molecules such as heparin (Knaus et al ., 1990) and certain animal toxins (Hamilton & Perez, 1987), have been shown to stimulate L‐type Ca 2+ channels in various mammalian tissues. Among the synthetic Ca 2+ channel ligands, some dihydropyridine derivatives such as Bay K 8644 (Hess et al ., 1984), CGP 28392 (Kokubun & Reuter, 1984), RS 30026 (Patmore et al ., 1990) and (+) 1,4‐dihydro‐2,6‐dimethyl‐5‐nitro‐4‐(benzofuran‐5‐yl)pyridine‐3‐carboxylate (Visentin et al ., 1999) as well as FPL 64176, a benzoylpyrrole compound (Rampe & Lacerda, 1991), have been shown to possess predominantly agonist‐like activity.…”

Kinetic modulation of guinea‐pig cardiac L‐type calcium channels by fendiline and reversal of the effects of Bay K 8644

“…Antagonist 1,4-dihydropyridines have been shown either not to affect the time course of activation (Lee & Tsien, 1983;Uehara & Hume, 1985), or to speed it up slightly (Hess et al, 1984). Agonist 1,4-dihydropyridines, on the other hand, have been reported generally to speed up activation accompanied by a shift of the steady state activation curve to more negative potentials (Hess et al, 1984;Lacerda & Brown, 1989;Patmore et al, 1990). These observations are suggestive of an 'on'-reaction of agonist dihydropyridines with some pre-open state.…”

Mefenamic acid as a novel activator of L‐type voltage‐dependent Ca2+ channels in smooth muscle cells from pig proximal urethra

“…Newly synthesized compounds for voltage-dependent Ca 2 þ channels Several newly synthesized compounds, some dihydropyridine derivatives such as Bay K 8644 (Hess et al, 1984), CGP 28392 (Kokubun & Reuter, 1984), RS 30026 (Patmore et al, 1990), ( þ ) 1,4-dihydro-2, 6-dimethyl-5-nitro-4-(benzofuran-5-yl) pyridine-3-carboxylate (Visentin et al, 1999) and a benzoylpyrrole compound (FPL 64176; Rampe & Lacerda, 1991) have been shown to possess predominantly agonistic activity of L-type Ca 2 þ channels. In the present experiments, we have been able to demonstrate that mefenamic acid, one of the most Effects of mefenamic acid and Bay K8644 on the voltagedependent activation and inactivation of the Ba 2 þ inward currents in pig urethra.…”