Search results for "Calcium Channel Blockers"
showing 10 items of 102 documents
(±)- BIGI-3h: Pentatarget-Directed Ligand combining Cholinesterase, Monoamine Oxidase, and Glycogen Synthase Kinase 3β Inhibition with Calcium Channe…
2021
Multitarget-directed ligands (MTDLs) are considered a promising therapeutic strategy to address the multifactorial nature of Alzheimer's disease (AD). Novel MTDLs have been designed as inhibitors of human acetylcholinesterases/butyrylcholinesterases, monoamine oxidase A/B, and glycogen synthase kinase 3β and as calcium channel antagonists via the Biginelli multicomponent reaction. Among these MTDLs, (±)-BIGI-3h was identified as a promising new hit compound showing in vitro balanced activities toward the aforementioned recognized AD targets. Additional in vitro studies demonstrated antioxidant effects and brain penetration, along with the ability to inhibit the aggregation of both τ protein…
Selective chiral inhibition of Ca2+ entry promoted by bisbenzyltetrahydroisoquinolines in rat uterus.
1992
Abstract The effects of diltiazem and six bisbenzyltetrahydroisoquinoline alkaloids (antioquine, 7-O-methylantioquine, dimethylantioquine, monterine, granjine and cordobimine) were studied in rat isolated uterus in order to clarify the mechanisms of their relaxant actions. All the compounds tested completely relaxed KCl-induced contractions and totally or partially inhibited oxytocin-induced rhythmic contractions. Only alkaloids with absolute configurations (1R,1′S or 1R,1′R) acted intracellularly, promoting relaxation of contractile responses induced by oxytocin in a Ca2+-free medium, as does papaverine. Alkaloids of the antioquine series (1S,1′R) selectively inhibited Ca2+ entry. The grea…
Alteration of loosely bound calcium in the guinea pig organ of Corti after treatment with diltiazem as calcium channel blocker
1997
After oral administration of the organic calcium channel blocker diltiazem to guinea pigs for 7 days, calcium ions were precipitated with potassium antimonate in the cochleae. The spatial distribution of the precipitates was studied by energy-filtering transmission electron microscopy and the amount of the ultrastructural reaction products formed was determined semiquantitatively by an image processing system. Compared with untreated control ears, the number of the formed precipitates was reduced drastically in the inner hair cells after diltiazem treatment. In addition, electron microscopic analysis revealed that the number of calcium precipitates attached at the basolateral membrane of th…
Different mechanism of relaxation induced by aporphine alkaloids in rat uterus.
1993
Abstract We have examined the uterine relaxant action of three aporphine molecules (S-glaucine, S-boldine and R-apomorphine) in two experimental conditions, with and without calcium in the bathing solution, and compared these effects with those obtained with the calcium antagonists verapamil and diltiazem. The present study shows that the alkaloids relax the uterine muscle but with different mechanisms of action. In Ca2+-containing solution all three alkaloids relaxed the uterus previously contracted by KCl or acetylcholine, but in Ca2+-free medium only R-apomorphine was able to relax oxytocin-induced contraction. The calcium antagonists, verapamil and diltiazem, relaxed KCl- or acetylcholi…
Acute and Chronic Captopril, but Not Prazosin or Nifedipine, Normalize Alterations in Adrenergic Intracellular Ca2+ Handling Observed in the Mesenter…
2004
The effect of hypertension and acute (36-h) or chronic (from age 6 to 16 weeks) antihypertensive treatment with prazosin (2 mg kg(-1) per day), nifedipine (50 mg kg(-1) per day), or captopril (50 mg kg(-1) per day) on Ca2+ mobilization due to alpha1-adrenoceptor activation was analyzed in functional studies using arterial rings [four conductance/distributing vessels: aorta, main mesenteric, iliac, and tail arteries and two resistance vessels; first and second small mesenteric artery branches obtained from spontaneously hypertensive rats (SHR, 6 and 16 weeks old) and age-matched Wistar Kyoto rats (WKY)]. Maximal response to noradrenaline in the presence of extracellular Ca2+ is not affected …
Special Considerations for Antihypertensive Agents in Dialysis Patients
2010
Hypertension is present in most patients with end-stage renal disease and likely contributes to the premature cardiovascular disease in dialysis patients. Previous practice guidelines have recommended that, in patients on chronic dialysis, blood pressure (BP) should be reduced below 130/80 mm Hg. This is based on opinions but not strong evidence, since no concrete information exists about which BP values should be the parameter to follow and which should be the target BP values. The majority of the antihypertensive agents can be used in this population, but the pharmacokinetics altered by the impaired kidney function and dialyzability influence the appropriate dosage as well as the time and…
Efficacy of combination therapy with angiotensin-converting enzyme inhibitor and calcium channel blocker in hypertension.
2012
There are few clinical trials that provide evidence to support the hypothesis that combined therapies offer a favorable risk-benefit ratio in the reduction of cardiovascular mortality and morbidity. Combined therapies containing an angiotensin-converting enzyme inhibitor (ACEI) with a calcium channel blocker (CCB) is one of the recommended combinations in the reappraisal of the European Society of Hypertension.The authors have performed a systematic review of the available clinical evidence on the use of combined therapies containing an ACEI with a CCB versus other combinations in the management of arterial hypertension (HT) and in the reduction of cardiovascular morbidity/mortality, accord…
Relaxation by Calcium Antagonists of Potassium-contracted Trachea from Normal and Sensitized Guinea-pigs: Influence of Epithelium and the Surface of …
1993
Abstract A technique by which drug access was restricted to either the mucosal or the adventitial surface of tracheal rings, isolated from normal (unsensitized) or sensitized guinea-pigs, was used to study the role of the epithelium in the relaxation produced by calcium antagonists (verapamil, nifedipine, cinnarizine and flunarizine) of K+-induced contraction. In trachea from normal guinea-pigs, the relaxation to verapamil for unrestricted or mucosal drug entry was reduced in the absence of epithelium, whereas the relaxation produced by nifedipine, cinnarizine or flunarizine was unchanged. In sensitized trachea, the relaxation elicited by the calcium antagonists tested was similar in intact…
The Sources of Ca2+ for Muscarinic Receptor-induced Contraction in the Rat Ileum
1996
Abstract The contractile responses obtained by activation of different muscarinic receptor subtypes in the longitudinal muscle of the rat ileum and especially the responses of this muscle to acetylcholine in a Ca2+-free medium have been investigated. In Ca2+-containing solution, acetylcholine elicited similar concentration-dependent contractile responses in the duodenum, jejunum and ileum strips of the rat intestine. The response to a maximal concentration of the agonist (1 μM) consisted of a rapid phasic response followed by a slower tonic one. Nifedipine completely relaxes or inhibits the sustained response and only partially diminishes the phasic one, which suggests that the phasic contr…
Ultrastructural evidence for protection of the outer hair cells of the inner ear during intense noise exposure by application of the organic calcium …
1999
Outer hair cells could be protected during intense noise exposure by the application of the calcium channel blocker diltiazem given before and after noise treatment. After various experimental approaches, the ultrastructural morphology was analysed for the different animal populations in the basal part of the second turn of the cochlea, which was the most destroyed area after an acute noise trauma caused by a gun shot (sound pressure at the ear drum 156 dB, frequency maximum between 4 and 6 kHz). Compared to untreated control specimens (experimental animal group I), the outer hair cells in the basal part of the second turn of the cochlea were mostly destroyed without any diltiazem applicati…