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 thispaper, anticonvulsant screening of 10 synthesized new derivatives of 1, 4-dihydropyridine-3,5-dicarboxamides was performed.Anticonvulsant activity was evaluated by intravenous and intraperitoneal pentylenetetr...

We measured [3H]PN200-110 binding and patch-clamp currents in rabbit ventricular myocytes to determine if there is a disparity between the density of dihydropyridine-specific receptors and functional L-type calcium channels, as has been reported for skeletal muscle. The dihydropyridine receptor density was 74.7 +/- 4.2 fmol/mg protein (mean +/- SEM, Kd = 1.73 +/- 0.29 nM, n = 6) in ventricular ...

The subcellular distribution of the 1,4-dihydropyridine receptor was determined in rabbit skeletal muscle in situ by immunofluorescence and immunoelectron microscopy. Longitudinal and transverse cryosections (5-8 microns) of rabbit gracilis muscle were labeled with monoclonal antibodies specific against either the alpha 1-subunit (170,000-D polypeptide) or the beta-subunit (52,000-D polypeptide...

To explore the role of calcium channels in hypertension, dihydropyridine ([3H]PN200-110) binding to heart, brain, and skeletal muscle microsomes of 4-, 8- and 15-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was measured. At a constant Ca2+ ion concentration (pCa 3.0), maximal binding (Bmax) of dihydropyridine binding to heart and brain microsomes was significantly ...

Two pyridine alkaloids were isolated from the derubberized resin of the hybrid Parthenium argentatum x P tomentosa. These alkaloids are (+/-)-N-[4-(1-aminoethyl) phenyl]-4-[3-methylbutenylidine]-1,4-dihydropyridine (guayulamine A) and (+/-)-N-[4-(1-aminoethyl) phenyl]-4-[4-methylpentenylidine]-1, 4-dihydropyridine (guayulamine B). The structures were established by one- and two-dimensional NMR ...

1,4-Dihydropyridine-sensitive voltage-dependent Ca2+ channels play a crucial role in the extracellular Ca(2+)-sensing of calcitonin-secreting parafollicular cells of the thyroid (C-cells). To characterize the Ca2+ channels in C-cells, we studied 1,4-dihydropyridine binding and performed electrophysiological experiments with Ca(2+)-sensitive C-cells (rat C-cell line rMTC 44-2) in comparison with...

Dihydropyridines (DHPs) are well known for their effects on L-typed voltage-dependent Ca2+ channels, However, these drugs also affect other voltage-dependent ion channels, including Shaker K+ channels. We examined the effects of DHPs on the Shaker K+ channels expressed in Xenopus oocytes. Intracellular applications of DHPs quickly and reversibly induced apparent inactivation in the Shaker K+ mu...

Changes in the substitutions at C-3 and C-5 positions of 4-(1-methyl-5-nitro-2-imidazolyl) dihydropyridine analogs of nifedipine have led to changes in potency of the compounds. The objective of the present study was to examine the hypotensive effects of 5 newly synthesized dihydropyridine derivatives of nifedipine in rats with phenylephrine-raised blood pressure. Anesthetized Sprague-Dawley ra...

A number of 1,4-dihydropyridine derivatives (9a?d, 10a?d and 11a?d) were designed synthesized by the reaction 1,3,4-oxadiazole-5-thiones 1,2,4-triazole-5-thiones to 2,6-dibromomethyl-3,5-diethoxycarbonyl-4-(3- -nitrophenyl)-1,4-dihydropyridine. The compounds characterized using FT-IR, 1H-NMR, 13C-NMR spectral data, ESI-MS elemental analysis. cytotoxicity was evaluated in human breast cancer (MC...

The reported structures of reaction products of enaminones with malononitrile in ethanolic piperidine are revised. A novel route to 2,3-dihydropyridazine-4-carboxylic acids 4a-c via reactions of 2-cyano-5-(dimethylamino)-5-arylpenta-2,4-dienamides 8a-c with nitrous acid or with benzenediazonium chloride is reported. Compounds 8a-c are converted to 1,2-dihydropyridine-3-carboxylic acid and 1,2-d...