BACKGROUND Both T-type calcium channels and cannabinoid receptors modulate signalling in the primary afferent pain pathway. Here, we investigate the analgesics activities of a series of novel cannabinoid receptor ligands with T-type calcium channel blocking activity. RESULTS Novel compounds were characterized in radioligand binding assays and in vitro functional assays at human and rat CB1 an...

Efflux of cytotoxic agents mediated by P-glycoprotein is believed to be an important mechanism of multidrug resistance, which remains a serious limitation to successful chemotherapy in cancers such as metastatic breast cancer. A series of 4-aryl-1,4-dihydropyridines and corresponding aromatized 4-arylpyridines have been synthesized based on structure modifications of niguldipine to enhance mult...

In formyl peptide stimulated human neutrophils the enhancement of 05 responses by ATP and ATPyS requires extracellular calcium. In contrast, the inhibitory effects of adenosine are independent of a calcium requirement. Rates of 0: generation are not affected by these adenine compounds. Rather, ATP and AT?$ cause a sustained period of generation whereas adenosine causes an abrupt early terminati...

: The mechanisms of the formation and transformation of calcium carbonates and the inhibition by the phosphorus containing compounds were studied. Supersaturated solutions form the unstable polymorph, amorphous calcium carbonate, at first, followed by the transformation to the metastable polymorph which finally transforms to stable form, calcite. Transformation proceeds by a mechanism of recrys...

The application of terahertz pulsed spectroscopy to polymorphic, liquid crystalline and amorphous forms of pharmaceutical compounds has been investigated. The different polymorphic forms of carbamazepine and enalapril maleate exhibit distinct terahertz absorbance spectra. In contrast to crystalline indomethacin and fenoprofen calcium, amorphous indomethacin and liquid crystalline fenoprofen cal...

Airway obstructive diseases, such as asthma and chronic obstructive pulmonary disease, cause the airways to narrow and make it difficult to breathe. Broncodilators are used to treat these conditions, but they often don’t work in severe cases and can cause serious side effects, such as abnormal heart rhythms and increased blood pressure. Recently, scientists discovered a potential alternative to...

Two new fused indoles were found to overcome multidrug resistance in P388/Adr cells in vitro. These agents potentiated the cytotoxicity of the antitumor drugs Adriamycin, vinblastine, and vincristine in multidrug-resistant cells with no effect on drug-sensitive parent P388 cells. They significantly increased the ATP-dependent accumulation of [3H]-vinblastine and inhibited efflux of the labeled ...

Mitochondrial sodium calcium exchange inhibitors are novel agents in the treatment of type-II diabetes due to their glucose dependent efficacy. While the compounds of this class are expected to correct hyperglycemia, they do not lower basal blood glucose level, thus avoiding the serious consequences of hypoglycemia. The 3DQSAR analysis of benzothiazepines and their derivatives as mitochondrial ...

A study was made of the interrelationship of serotonin, cAMP, and calcium ions in the regulation of regeneration of cilia by Tetrahymena pyriformis. All these compounds stimulated the regeneration, whereas a blocker of serotonin synthesis, p-chlorophenylalanine, and a calcium chelator, EGTA, inhibited the process. This inhibition could be overcome by the addition of any of the stimulatory compo...