Dihydropyridine-sensitive voltage-dependent L-type calcium channels are critical to excitation-secretion and excitation-contraction coupling. The channel molecule is a complex of the main, pore-forming subunit alpha 1 and four additional subunits: alpha 2, delta, beta, and gamma (alpha 2 and delta are encoded by a single messenger RNA). The alpha 1 subunit messenger RNA alone directs expression...

It is widely accepted that Ca2+ is released from the sarcoplasmic reticulum by a specialized type of calcium channel, i.e., ryanodine receptor, by the process of Ca2+-induced Ca2+ release. This process is triggered mainly by dihydropyridine receptors, i.e., L-type (long lasting) calcium channels, directly or indirectly interacting with ryanodine receptor. In addition, multiple endogenous and ex...

Equipped with excellent hydrocarbon solubility, the lithium hydride surrogate 1-lithium-2-tert-butyl-1,2-dihydropyridine (1tLi) functions as a precatalyst to convert Me2 NH⋅BH3 to [NMe2 BH2 ]2 (89 % conversion) under competitive conditions (2.5 mol %, 60 h, 80 °C, toluene solvent) to that of previously reported LiN(SiMe3 )2 . Sodium and potassium dihydropyridine congeners produce similar high y...

Herein, we report our preliminary results concerning the first promising asymmetric synthesis of highly functionalized 2-oxospiro-[indole-3,4'-(1',4'-dihydropyridine)] via the reaction of an enamine with isatylidene malononitrile derivatives in the presence of a chiral base organocatalyst. The moderate, but promising, enantioselectivity observed (30%-58% ee (enantiomeric excess)) opens the door...

In motoneurons, generation of plateau potentials is promoted by modulators that block potassium channels. In voltage-clamp experiments with triangular voltage ramp commands, we show that cis-(+/-)-1-aminocyclopentane-1, 3-dicarboxylic acid (cis-ACPD) and muscarine promote the generation of plateau potentials by increasing the dihydropyridine sensitive inward current, by increasing the input res...

Epilepsy is a chronic disorder of the brain affecting around 50 million people in the world. Up to 30% of epileptic patients do not respond to available drugs and medical therapies. In this paper, anticonvulsant screening of 10 synthesized new derivatives of 1, 4-dihydropyridine-3, 5-dicarboxamides was performed. Anticonvulsant activity was evaluated by intravenous and intraperitoneal pentylene...

Endothelin is a potent endothelium-derived vasoconstrictor peptide recently characterized from porcine and human vascular endothelial cells. Here we provide evidence that endothelin activates the dihydropyridine-sensitive, voltage-dependent Ca2+ channel in porcine coronary artery smooth muscle. The vasoconstrictor action of endothelin is efficiently antagonized by low doses of the dihydropyridi...

To compare the antianginal eŠects of 1,4-dihydropyridine-type calcium-channel blockers, we evaluated the eŠects of benidipine, amlodipine, nifedipine, and efonidipine on vasopressin-induced myocardial ischemia in rats, an experimental model of angina. Intravenous administration of benidipine (3 mg/kg), amlodipine (1000 mg/kg), and nifedipine (100 mg/kg) suppressed the vasopressin-induced S-wave...

hronic stable angina (CSA) represents the largest cardiovascular disorder in the United States and is the initial clinical presentation of ischemic heart disease in 50% of patients. CSA is the result of the progression of coronary atherosclerosis and becomes symptomatic once the luminal diameter of the vessel is occluded by >50%. Current medical therapy is targeted at reducing the frequency of ...

An efficient and expeditious catalyst-free procedure was developed for the one- pot synthesis of 1, 4-dihydropyridine derivatives via the three-component reaction of various aldehydes, ethyl acetoacetate, and ammonium acetate in PEG-400. The reaction was carried out at 110°С and the products were obtained in good to high yields.