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Potassium Channel Blocker (potassium + channel_blocker)
Selected AbstractsChemInform Abstract: Chlorahololides C,F: A New Class of Potent and Selective Potassium Channel Blockers from Chloranthus holostegius.CHEMINFORM, Issue 37 2008Sheng-Ping Yang Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Potassium channel blocker 4-aminopyridine is effective in interictal cerebellar symptoms in episodic ataxia type 2 , A video case reportMOVEMENT DISORDERS, Issue 9 2008Matthias Löhle MD Abstract Episodic ataxia type 2 (EA2) is an autosomal-dominant hereditary disorder clinically characterized by recurrent attacks of vertigo, imbalance and ataxia. Studies have shown that 4-aminopyridine (4-AP) is capable to prevent these attacks. However, there are no reports whether 4-AP is able to attenuate interictal cerebellar ataxia. Using the scale for assessment and rating of ataxia (SARA), we examined the efficacy of 4-AP on interictal ataxia in a 63-year-old female patient who suffered from EA2 since the age of 57. EA2 was diagnosed based on clinical criteria and not genetically proven. When treatment with 4-AP was paused the patient was suffering from marked gait and stance ataxia. After re-initiation of treatment with 5 mg 4-AP t.i.d., there was pronounced improvement in gait and stance ataxia. Within 24 hours SARA score lowered from 8.5 to 4.5 points. We conclude that 4-AP may be beneficial for interictal cerebellar ataxia in late onset EA2. © 2008 Movement Disorder Society [source] Amiodarone Attenuates Fluoride-induced Hyperkalemia in VitroACADEMIC EMERGENCY MEDICINE, Issue 2 2003Mark Su MD Abstract Poisoning by hydrofluoric acid or fluoride salts results in hypocalcemia, hypomagnesemia, and hyperkalemia with subsequent cardiac dysrhythmias. In previous studies, quinidine attenuated fluoride-induced hyperkalemia in vitro, and enhanced survival in animals. Like quinidine, amiodarone is a potassium channel blocker, although amiodarone is more familiar to clinicians due to its recent inclusion in advanced cardiac life support (ACLS) protocols. Objectives: This in-vitro study of human erythrocytes was designed to determine whether amiodarone could attenuate fluoride-induced hyperkalemia. Methods: Six healthy volunteers each donated 60 mL of blood on three occasions. Each specimen was divided into 12 tubes, incubated at 37°C, and oxygenated with room air. An aqueous sodium fluoride (F,) solution was added to tubes 1,9. Incremental amounts of quinidine were added to tubes 1,4 (Q1,Q4) to attain calculated concentrations of 0.73 ,g/mL, 1.45 ,g/mL, 2.9 ,g/mL, and 5.8 ,g/mL, respectively. Incremental amounts of amiodarone were added to tubes 5,8 (A1,A4) to attain calculated concentrations of 0.38 ,g/mL, 0.75 ,g/mL, 1.5 ,g/mL, and 3.0 ,g/mL, respectively. Tubes 9,12 were controls for each of F,, amiodarone, quinidine alone, and no additive, respectively. Extracellular potassium concentration ([K+]) was followed, and an objective endpoint was defined as the rise in potassium concentration at 6 hours. Results: Fluoride produced a significant change in [K+] by 6 hours in all samples. Quinidine produced a J-shaped curve in its ability to attenuate the rise in [K+], with only one concentration, Q3, demonstrating significance versus tube 9 (control). Amiodarone also demonstrated a J-shaped dose,response effect, with statistical significance at A1, A2, and A3 versus tube 9 (control). There was no significant difference among the effective concentrations (Q3, A1, A2, and A3) of both drugs. Conclusions: In this in-vitro model using human blood, amiodarone and quinidine both attenuated F, -induced hyperkalemia. Further study is indicated to determine whether amiodarone enhances survival in F, -poisoned animals. [source] The Time Course of New T-Wave ECG Descriptors Following Single- and Double-Dose Administration of Sotalol in Healthy SubjectsANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 1 2010Fabrice Extramiana M.D., Ph.D. Introduction: The aim of the study was to assess the time course effect of IKr blockade on ECG biomarkers of ventricular repolarization and to evaluate the accuracy of a fully automatic approach for QT duration evaluation. Methods: Twelve-lead digital ECG Holter was recorded in 38 healthy subjects (27 males, mean age = 27.4 ± 8.0 years) on baseline conditions (day 0) and after administration of 160 mg (day 1) and 320 mg (day 2) of d-l sotalol. For each 24-hour period and each subject, ECGs were extracted every 10 minutes during the 4-hour period following drug dosage. Ventricular repolarization was characterized using three biomarker categories: conventional ECG time intervals, principal component analysis (PCA) analysis on the T wave, and fully automatic biomarkers computed from a mathematical model of the T wave. Results: QT interval was significantly prolonged starting 1 hour 20 minutes after drug dosing with 160 mg and 1 hour 10 minutes after drug dosing with 320 mg. PCA ventricular repolarization parameters sotalol-induced changes were delayed (>3 hours). After sotalol dosing, the early phase of the T wave changed earlier than the late phase prolongation. Globally, the modeled surrogate QT paralleled manual QT changes. The duration of manual QT and automatic surrogate QT were strongly correlated (R2= 0.92, P < 0.001). The Bland and Altman plot revealed a nonstationary systematic bias (bias = 26.5 ms ± 1.96*SD = 16 ms). Conclusions: Changes in different ECG biomarkers of ventricular repolarization display different kinetics after administration of a potent potassium channel blocker. These differences need to be taken into account when designing ventricular repolarization ECG studies. Ann Noninvasive Electrocardiol 2010;15(1):26,35 [source] Mechanisms involved in the regulation of bovine pulmonary vascular tone by the 5-HT1B receptorBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2010C McKenzie Background and purpose:, 5-HT1B receptors may have a role in pulmonary hypertension. Their relationship with the activity of BKCa, a T-type voltage-operated calcium channel (VOCC) and cyclic nucleotide-mediated relaxation was examined. Experimental approach:, Ring segments of bovine pulmonary arteries were mounted in organ baths in modified Krebs,Henseleit buffer (37oC) under a tension of 20 mN and gassed with 95% O2/5% CO2. Isometric recordings were made using Chart 5 software. Key results:, Contractile responses to 5-HT (10 nM,300 µM) were inhibited similarly by the 5-HT1B receptor antagonist SB216641 (100 nM) and the T-type VOCC blockers mibefradil (10 µM) and NNC550396 (10 µM) with no additive effect between SB216641 and mibefradil. Inhibition by SB216641 was prevented by the potassium channel blocker, charybdotoxin (100 nM). 5-HT1B receptor activation and charybdotoxin produced a mibefradil-sensitive potentiation of responses to U46619. Bradykinin (0.1 nM,30 µM), sodium nitroprusside (0.01 nM,3 µM), zaprinast (1 nM,3 µM), isoprenaline (0.1 nM,10 µM) and rolipram (1 nM,3 µM) produced 50% relaxation of arteries constricted with 5-HT (1,3 µM) or U46619 (30,50 nM) in the presence of 5-HT1B receptor activation, but full relaxation of arteries constricted with U46619, the 5-HT2A receptor agonist 2,5 dimethoxy-4 iodoamphetamine (1 µM) or 5-HT in the presence of 5-HT1B receptor antagonism. Enhanced relaxation of 5-HT-constricted arteries by cGMP-dependent pathways, seen in the presence of the 5-HT1B receptor antagonist, was reversed by charybdotoxin whereas cAMP-dependent relaxation was only partly reversed by charybdotoxin. Conclusions and implications:, 5-HT1B receptors couple to inhibition of BKCa, thus increasing tissue sensitivity to contractile agonists by activating a T-type VOCC and impairing cGMP-mediated relaxation. Impaired cAMP-mediated relaxation was only partly mediated by inhibition of BKCa. [source] Gadolinium, a mechano-sensitive channel blocker, inhibits osmosis-initiated motility of sea- and freshwater fish sperm, but does not affect human or ascidian sperm motilityCYTOSKELETON, Issue 4 2003Zoltán Krasznai Abstract Exposure to hypo-osmotic or hyperosmotic environment triggers the initiation of fish sperm motility. In this article, we report that calcium and potassium channel blockers do not influence motility of puffer fish sperm but calmodulin antagonists reversibly decrease it, suggesting that calmodulin,Ca2+ interactions are prerequisite for the initiation of sperm motility in this species. Gadolinium (a stretch activated ion channel blocker) decreased the motility of puffer fish sperm from 92 ± 3% to 6 ± 3% and that of carp sperm from 91 ± 7% to 3.5 ± 4.3% in a dose-dependent manner (10,40 ,M). The effect of gadolinium was reversible, suggesting that stretch activated ion channels participate in the initiation of sperm motility of the two species. Gadolinium inhibits changes in the isoelectric point of certain proteins of puffer fish sperm, which occur when sperm motility is initiated in a hypertonic solution. Anisotropy measurements showed that hypo-osmotic treatment, which initiates carp sperm motility, increased membrane fluidity. When hypo-osmotic treatment was given in the presence of gadolinium, the sperm membrane remained as rigid as in quiescent cells, while motility was blocked. By contrast, gadolinium did not influence the motility parameters of Ciona or human sperm. Based on these lines of evidence, we suggest that conformational changes of mechanosensitive membrane proteins are involved in osmolality-dependent but not osmolality-independent sperm. Cell Motil. Cytoskeleton 55:232,243, 2003. © 2003 Wiley-Liss, Inc. [source] Injury-induced neurogenesis in Bax-deficient mice: evidence for regulation by voltage-gated potassium channelsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2007Jian Shi Abstract Adult neural stem and progenitor cells may help remodel the brain in response to injury. The pro-apoptotic molecule Bax has recently been identified as a key player in adult neural stem cell survival. In Bax-deficient mice that have undergone traumatic brain injury, we find increased numbers of neural progenitor cells in the dentate gyrus and improved remodeling of the hippocampus. Exogenous potassium chloride mimics spreading depression (SD)-like events in vitro, and Bax-deficient neural stem cells proliferate in response to these events more robustly than wild-type neural stem cells. Selective potassium channel blockers interrupt SD-mediated stimulation of stem cells. In addition, the potassium channel Kv4.1 is expressed within neural stem and progenitor cells in the dentate gyrus and is increased in Bax-deficiency. These data suggest that the neuroprotection observed after injury in Bax-deficiency may be due to increased neurogenesis via activation of the Kv4 family of potassium channels. [source] Hydrogen,potassium ATPase inhibitors induce relaxation on rabbit prostatic strips in vitroINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2002Ihsan Bagcivan Summary Background : To determine the relaxant effect of omeprazole and lansaprazole, hydrogen,potassium (H+,K+) ATPase inhibitors, on rabbit prostatic tissue in vitro. Methods : Male New Zealand white rabbits were sacrificed and their prostatic tissues were removed. The prostatic stromal strips were mounted in organ baths and relaxation responses were obtained in precontracted tissues with phenylephrine, carbachol and potassium chloride (KCl). Relaxation responses were controlled in the presence of various antagonists to explain the mechanism for relaxation exerted by omeprazole and lansaprazole. Results : Omeprazole and lansaprazole caused similar relaxation responses in the prostatic strips precontracted with phenylephrine, carbachol and KCl. The addition of prostaglandin synthase inhibitor indomethacin, nitric oxide synthase inhibitor L-NAME, potassium channel blockers, glibenclamide and tetraethylammonium into the organ baths did not change the relaxations induced by omeprazole and lansaprazole in vitro. Conclusion : Omeprazole and lansaprazole cause a relaxation in prostatic stromal tissue precontracted with phenyephrine, carbachol and KC1 in vitro. This relaxant effect is independent of H+,K+ ATPase inhibition. Additionally, cyclooxygenase and nitric oxide pathways do not contribute to this relaxant effect. Further studies are required to determine whether these drugs may have a beneficial effect in the non-operative treatment of benign prostatic hyperplasia. [source] | |||||||||||||