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quinidine/carie dentaire
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Modulation of nose-to-brain delivery of a P-glycoprotein (MDR1) substrate model drug (quinidine) in rats.
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During the last decades several new drug formulations were developed to target the central nervous system (CNS) from the nasal cavity. However, in these studies less attention was paid to the possible drug-drug interactions in case of multi-drug therapy. In our pilot study first we compared a nasal
Carrier mediated transport of chlorpheniramine and chlorcyclizine across bovine olfactory mucosa: implications on nose-to-brain transport.
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Delivery to the CNS via the nasal cavity has been pursued as a means to circumvent the blood-brain barrier (BBB), yet the mechanism of drug transport across this novel route is not well understood. Hydroxyzine and triprolidine have been reported to readily reach the CNS following nasal
Molecular docking and enzyme kinetic studies of dihydrotanshinone on metabolism of a model CYP2D6 probe substrate in human liver microsomes.
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The effects of Danshen and its active components (tanshinone I, tanshinone IIA, dihydrotanshinone and cryptotanshinone) on CYP2D6 activity was investigated by measuring the metabolism of a model CYP2D6 probe substrate, dextromethorphan to dextrorphan in human pooled liver microsomes. The ethanolic
Effects of atorvastatin and simvastatin on atrial plateau currents.
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Recent evidence has shown that the inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) might exert antiarrhythmic effects both in experimental models and in humans. In this study we analyzed the effects of atorvastatin and simvastatin acid (SVA) on the currents responsible
Evidence that serine 304 is not a key ligand-binding residue in the active site of cytochrome P450 2D6.
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Homology models of cytochrome P450 2D6 (CYP2D6) have identified serine 304 as an active-site residue and implicated a putative role for this residue in substrate enantioselectivity and the differential inhibition of enzyme activity by the diastereoisomers quinine and quinidine. The role of serine
TCM treatment of extrasystole with huanglian shengmai yin--a report of 357 cases.
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The previous experimental studies have demonstrated that addition of Huang Qi ([symbol: see text] Radix Astragali) to the formulated recipe Sheng Mai Yin ([symbol: see text] Decoction for Pulse-activation) exerts the effects of strengthening the myodynamia, increasing the coronary flow, improving
Inhibitor effects on the ionic exchanges through the human amniotic epithelial cell membranes.
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Direct measurements of cell podocyte/or microvillous membrane ionic exchanges were performed on the membranes of isolated human amniotic epithelial cells. The ionic exchanges were determined from the measures of cellular input conductances. The effects of various inhibitors: ouabain, amiloride,
Metastasis to the right stellate ganglion and vagal nerve: pathological alterations causing sudden death. A case report.
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Sudden death in a 66-year-old woman with squamous cell carcinoma of the oral cavity and exclusive metastatic involvement of the right stellate ganglion and right nerve vagus is reported. The patient also suffered from paroxysmal atrial fibrillation treated with quinidine. An autopsy showed exclusive
Dominant right ventricular dilated cardiomyopathy: clinical, echocardiographic and haemodynamic profile.
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Ten patients of dominant right ventricular dilated cardiomyopathy (RVDCM) seen over a period of three years in this institution are described. There were six males and four females in the age range of 6.50 years. Presenting features were right ventricular failure (7), paroxysmal supraventricular
Shab K (+) channel slow inactivation: a test for U-type inactivation and a hypothesis regarding K (+) -facilitated inactivation mechanisms.
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Herein, we report the first characterization of Shab slow inactivation. Open Shab channels inactivate within seconds, with two voltage-independent time constants. Additionally, Shab presents significant closed-state inactivation. We found that with short depolarizing pulses, shorter than the slowest
Breaking the silence: functional expression of the two-pore-domain potassium channel THIK-2.
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THIK-2 belongs to the 'silent' channels of the two-pore-domain potassium channel family. It is highly expressed in many nuclei of the brain but has so far resisted all attempts at functional expression. THIK-2 has a highly conserved 19-amino-acid region in its N terminus (residues 6-24 in the rat
Functional and structural characterisation of common cytochrome P450 2D6 allelic variants-roles of Pro34 and Thr107 in catalysis and inhibition.
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One major source of inter-individual variability in drug pharmacokinetics is genetic polymorphism of the cytochrome P450 (CYP) genes. This study aimed to elucidate the enzyme kinetic and molecular basis for altered activity in three major alleles of CYP2D6, namely CYP2D6*2, CYP2D6*10 and CYP2D6*17.
Iatrogenic QT Abnormalities and Fatal Arrhythmias: Mechanisms and Clinical Significance.
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Severe and occasionally fatal arrhythmias, commonly presenting as Torsade de Pointes [TdP] have been reported with Class III-antiarrhythmics, but also with non-antiarrhythmic drugs. Most cases result from an action on K(+) channels encoded by the HERG gene responsible for the IKr repolarizing
Molecular determinants for high-affinity block of human EAG potassium channels by antiarrhythmic agents.
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Undesired block of human ERG1 potassium channels is the basis for cardiac side effects of many different types of drugs. Therefore, it is important to know exactly why some drugs particularly bind to these channels with high affinity. Upon expression in mammalian cells and Xenopus laevis oocytes, we
K⁺-dependent selectivity and external Ca²⁺ block of Shab K⁺ channels.
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Potassium channels allow the selective flux of K⁺ excluding the smaller, and more abundant in the extracellular solution, Na⁺ ions. Here we show that Shab is a typical K⁺ channel that excludes Na⁺ under bi-ionic, Na(o)/K(i) or Na(o)/Rb(i), conditions. However, when internal K⁺ is replaced by Cs⁺
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