Search results for "Verapamil"
showing 10 items of 68 documents
Action of tertiary phenylalkylamines on cardiac transient outward current from outside the cell membrane.
1996
The effects of the phenylalkylamines verapamil (V), gallopamil (G), and devapamil (D) and their corresponding quaternary derivatives on the transient outward current (Ito) were examined in rat ventricular cardiomyocytes using the whole-cell patch-clamp technique. The question was addressed, whether phenylalkylamines act on Ito from the inside or the outside or from both sides of the cell membrane. To this end, the myocytes were either superfused extracellularly or perfused intracellularly with drug-containing solutions. In addition, the effects of verapamil were investigated at different pH-values. V, G, and D (30 microM each), applied extracellularly, reduced the steady state current of It…
Kinetics and state-dependent effects of verapamil on cardiac L-type calcium channels.
1996
The voltage dependence and the kinetics of block by verapamil of L-type calcium current (ICa) were investigated in ventricular myocytes from rat hearts using the whole-cell patch-clamp technique. ICa was elicited repetitively in response to depolarizing voltage pulses from -80 mV to 0 mV at different pulse intervals and durations. Verapamil reduced the magnitude of ICa in a frequency-dependent manner without tonic component. The time course of ICa remained unchanged suggesting that not open but inactivated channels were affected by the drug. The interaction of verapamil with inactivated channels was investigated by the application of twin pulses. In the presence of verapamil, the duration o…
Release of non-neuronal acetylcholine from the isolated human placenta is mediated by organic cation transporters
2001
1. The release of acetylcholine was investigated in the human placenta villus, a useful model for the characterization of the non-neuronal cholinergic system. 2. Quinine, an inhibitor of organic cation transporters (OCT), reduced acetylcholine release in a reversible and concentration-dependent manner with an IC(50) value of 5 microM. The maximal effect, inhibition by 99%, occurred at a concentration of 300 microM. 3. Procaine (100 microM), a sodium channel blocker, and vesamicol (10 microM), an inhibitor of the vesicular acetylcholine transporter, were ineffective. 4. Corticosterone, an inhibitor of OCT subtype 1, 2 and 3 reduced acetylcholine in a concentration-dependent manner with an IC…
Relaxant and antiadrenergic effects of ranolazine in human saphenous vein.
2019
Abstract OBJECTIVES Ranolazine improves vascular function in animal models. We evaluate the effects of ranolazine on vascular function and adrenergic response in human saphenous vein. METHODS Rings from 53 patients undergoing coronary artery bypass grafting were mounted in organ baths. Concentration–response curves to ranolazine were constructed in rings precontracted with phenylephrine, endothelin-1, vasopressin, KCl and the thromboxane A2 analogue U-46619. In rings precontracted with phenylephrine, relaxation to ranolazine was tested in the absence and presence of endothelial factors inhibitors, K+ channel blockers and verapamil. The effects of ranolazine on frequency–response and concent…
Transintestinal secretion of ciprofloxacin, grepafloxacin and sparfloxacin: in vitro and in situ inhibition studies.
2003
The influence of the secretion process on the absorption of ciprofloxacin, grepafloxacin and sparfloxacin has been evaluated by means of inhibition studies. Two well known P-glycoprotein inhibitors (cyclosporine, verapamil), a mixed inhibitor of P-glycoprotein and the organic cation transporter OCT1 (quinidine) and a well established MRP substrate (p-aminohipuric acid) have been selected in order to distinguish the possible carriers implicated. An in situ rat gut perfusion model and CACO-2 permeability studies are used. Both methods suggest the involvement of several types of efflux transporters for every fluoroquinolone. The relevance of the secretory pathway depends on the intrinsic perme…
Metabolism of propafenone and verapamil by cryopreserved human, rat, mouse and dog hepatocytes: comparison with metabolism in vivo
2003
In the present study we examined the metabolism of [(14)C]propafenone (P) and [(14)C]verapamil (V) using cryopreserved human, dog (Beagle), rat (Sprague-Dawley) and mouse (NMRI) hepatocytes. The percentage ratios of the metabolites were identified after extraction by HPLC with UV and radioactivity detection. Phase-II metabolites were cleaved using beta-glucuronidase. Metabolism of the drugs by cryopreserved hepatocytes was compared with that in the respective species in vivo. All phase-I and -II metabolites known from in vivo experiments: 5-hydroxy-P (5-OH-P); 4'-hydroxy-P (4'-OH-P); N-despropyl-P (NdesP) and the respective glucuronides, were identified after incubation with cryopreserved h…
Effect of two antihypertensive combinations on metabolic control in type-2 diabetic hypertensive patients with albuminuria: a randomised, double-blin…
2001
The objective of this study was to compare, at equal blood pressure (BP) reduction, the effect of two different combinations on metabolic control and albuminuria in type 2 diabetic hypertensive patients with albuminuria. This was a prospective, randomised, double-blind, parallel, controlled trial carried out in 11 Spanish hospitals. A total of 103 type 2 diabetic patients with stable albuminuria and BP not controlled on monotherapy were randomised of which 93 finished the study. After a 4-week single-blind placebo period, patients were randomised to verapamil SR/trandolapril 180/2 mg (VT) or to enalapril/hydroclorothiazide 20/12.5 mg (EH). Treatment duration was 6 months. The main outcome m…
Kinetic Characterization of Secretory Transport of a New Ciprofloxacin Derivative (CNV97100) across Caco-2 Cell Monolayers**This work has been submit…
2002
The kinetics of transport of a new fluoroquinolone antibiotic (CNV97100) and its analogs were characterized using the Caco-2 cell culture model. Unidirectional permeabilities of these analogs were greater (p < 0.05) than that of ciprofloxacin. The absorptive permeabilities (P(AB)) of 4'-N-substituted analogs (CNV97101-104) were 400-600% greater, whereas the secretory permeability (P(BA)) was 25-80% greater than unsubstituted analogs because CNV97101-104 were poor substrates for efflux transporters (efflux ratio approximately 1). The transport of compounds without 4'-N-substitution (i.e., ciprofloxacin and CNV97100) favored secretion (efflux ratio approximately 4). Further characterization o…
No evidence for efficacy of intrathecal verapamil in the treatment of tonic-clonic status epilepticus
1992
In two patients with refractory generalized tonic-clonic status epilepticus, 15 mg of the calcium antagonist verapamil was given by suboccipital intrathecal administration. During a 2–6-h observation period, seizure frequency did not decrease. However, in one patient, verapamil induced severe hypotension. Subsequent thiopental anesthesia suppressed convulsions immediately. Our results indicate that, in contradistinction to animal studies with different administration techniques, intrathecal administration of verapamil does not produce any anticonvulsant effect in humans.
Differential antiepileptic effects of the organic calcium antagonists verapamil and flunarizine in neurons of organotypic neocortical explants from n…
1988
Effects of the organic calcium antagonists verapamil and flunarizine on pentylenetetrazol induced paroxysmal depolarizations were tested in organotypic neocortical explants taken from neonatal rats. In these in vitro experiments the papaverin derivative verapamil depressed, and finally abolished, epileptic discharges in all cases. The piperazine derivative flunarizine, however, which is known to suppress epileptic discharges in hippocampal CA3 neurons (Bingmann and Speckmann 1986), showed no significant antiepileptic effects in the explanted neocortical neurons. Thus, the present findings may indicate that the suppressive action of flunarizine on the generation of paroxysmal depolarizations…