Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: CAS:41708-72-9 (Tocainide)
 93 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The inhibitory actions of two class IB antiarrhythmics, lidocaine and tocainide, on Mg(2+)-dependent ATP hydrolysis by myocardial Na(+)-K(+)-ATPase (EC 3.6.1.3), were tested in guinea-pig heart preparations incubated in media containing 2.5, 5.0 and 10 mM K+. 2. The IC50 values for lidocaine were 2.4 +/- 0.4 mM at 2.5, 4.1 +/- 0.8 mM at 5.0 and 5.3 +/- 0.5 mM at 10 mM K+. The corresponding IC20 values were 0.82 +/- 0.12 mM at 2.5, 1.3 +/- 0.2 mM at 5.0 and 1.7 +/- 0.4 mM at 10.0 mM K+ respectively. Tocainide exerted similar action with IC50 values of 3.1 +/- 0.9 mM at 2.5, 7.6 +/- 1.4 mM at 5.0 and 15.5 +/- 1.6 mM at 10.0 mM K+ and IC20 values of 0.71 +/- 0.19 at 2.5, 2.7 +/- 0.5 mM at 5.0 and 12.3 +/- 1.2 mM at 10.0 mM K+ respectively. 3. Thus, the inhibitory potencies of the drugs on myocardial Na(+)-K(+)-ATPase activity increased significantly with reduction in the K+ concentration. These results demonstrate therefore that the inhibitory actions of both lidocaine and tocainide depend on the K+ concentration of the incubation medium. 4. These findings may be indicative of the importance of K+ in some of the cardiac effects of the antiarrhythmic agents, particularly their tendency to induce or enhance already existing cardiac arrhythmias.
 ...
PMID:The effect of modifying potassium concentration on the inhibition of myocardial Na(+)-K(+)-ATPase by two class IB antiarrhythmic drugs: lidocaine and tocainide. 166 1

To study the mechanism of use dependence, we investigated the influence of 0.5 mM tocainide on the amplitude of sodium currents elicited by membrane depolarizations with standard test pulses in voltage-clamped human myoballs. For comparison, the experiments were also conducted with 1 mM benzocaine, a drug with almost no use dependence. These concentrations were so chosen that without stimulation and at a holding potential of -135 mV, either drug blocked about 50% of the channels (tonic block). With repetitive stimulation at 1 Hz, tocainide blocked about 75% of the channels that had remained open in the rested state (phasic block), while benzocaine had little such effect. The potential dependence of steady-state inactivation (h infinity curves) of the sodium channels in these myoballs depended on the duration of the prepotential indicating that they possess at least two states of inactivation: fast and intermediate. The two drugs differed in their effects on these two states. Benzocaine always produced a left-shift of the h infinity curve, no matter whether the duration of the conditioning pulse was short (8 ms) or long (512 ms) indicating that it can bind when the channel is in the state of fast inactivation. Tocainide shifted the h infinity curve only with long prepulses, i.e. when the sodium channels were in the state of intermediate inactivation. The recovery from inactivation, a process governed by two time constants in the absence of drugs, was also differently influenced by the two drugs. In the presence of tocainide, the channels mainly recovered with the slow time constant and this time constant was significantly increased, whereas benzocaine did not substantially modify this biphasic process.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The different use dependences of tocainide and benzocaine are correlated with different effects on sodium channel inactivation. 166 29

An in vitro model was used to examine the electrophysiological effects of anti-arrhythmic drugs in infarcted tissue. After 24 h of coronary artery occlusion in the dog, endocardial preparations were removed from the infarcted zone. Intracellular action potentials recorded from surviving Purkinje fibres on the endocardial surface showed reduced maximum upstroke velocity (Vmax), increased action potential duration and enhanced automaticity. The rate-dependent effect of lidocaine on Vmax and conduction was more prominent in Purkinje fibres that survived myocardial infarction than in normal Purkinje fibres. Tocainide, flecainide, and O-demethyl encainide reduced Vmax in both normal Purkinje fibres and Purkinje fibres surviving infarction. Similar to lidocaine, these drugs showed the greatest reduction of Vmax in Purkinje fibres surviving infarction at the shortest stimulation cycle length tested. In contrast, maximal drug effects on action potential duration were observed when long stimulation cycle lengths were used. Our results indicate that most Class I anti-arrhythmic drugs showed rate-dependent properties in normal Purkinje fibres as well as in Purkinje fibres surviving infarction. The increased sensitivity of the ischemic myocardium to anti-arrhythmic drugs resulting in greater reductions of Vmax and conduction may contribute to a greater potency of anti-arrhythmic drugs in the suppression of arrhythmias associated with ischemia. Conversely, while slowing of conduction can abolish re-entry arrhythmias by producing a bidirectional block, further slowing of conduction by anti-arrhythmic drugs can favour the development of new re-entry pathways and may contribute to their pro-arrhythmic effects.
 ...
PMID:Effects of class I anti-arrhythmic drugs in infarcted tissue. 174 23

Significant improvement in symptoms of disabling cramps and muscle spasms was obtained in 9 patients with motor neuron diseases, tetany, and myotonic disorders who were treated with tocainide, a lidocaine analog. No significant side effects were observed except for light-headedness and fatigue in 1 patient, who also showed slight prolongation of intraventricular conduction time. Tocainide is useful in treating disabling muscle spasms and cramps associated with conditions characterized by neuromuscular irritability. This effect is probably based on stabilization of the membrane potential at various levels (motor neurons, peripheral nerve, or muscle fiber membrane).
 ...
PMID:Tocainide therapy in muscle cramps and spasms due to neuromuscular disease. 176 57

To compare the therapeutic efficacy and safety of intravenous tocainide with that of intravenous lidocaine in patients with ventricular arrhythmias after cardiac surgery, 25 patients were randomized to either agent in a double-blind manner. Tocainide was given in 16 patients as a 250 mg bolus followed by a loading infusion of 500 mg over 15 minutes and a maintenance infusion of 33.3 mg/min. Lidocaine was administered in 9 patients as a 100 mg bolus followed by a loading infusion of 60 mg over 15 minutes and a maintenance infusion of 1.4 mg/min. Therapy was continued for 24 hours in initially responding patients. With analysis of 24-h taped electrocardiograms it was found that single premature ventricular complexes (PVCs) were suppressed by tocainide by more than 80% in 94% of patients and by lidocaine in 75% of patients (p = NS). Couplets and ventricular tachycardia events were eliminated in all patients by either drug. Multiform PVCs were abolished in 94% of the patients after tocainide and in 75% after lidocaine (p = NS). Average overall success over the 24 hours with more than 80% suppression of single PVCs and simultaneous elimination of higher forms of arrhythmia was 71% with tocainide and 59% with lidocaine (p = NS). Adverse effects were negligible, with only one patient in the lidocaine group developing diaphoresis without necessitating termination of therapy. Treatment rapidly produced and then maintained blood levels of 4-10 mg/l for tocainide and 1-4 mg/l for lidocaine. We conclude that intravenous tocainide is well tolerated and has comparable efficacy to lidocaine in the acute therapy of postcardiac surgery ventricular arrhythmias.
 ...
PMID:Randomized double-blind study of intravenous tocainide versus lidocaine for suppression of ventricular arrhythmias after cardiac surgery. 210 35

We examined the in vivo electrophysiologic effects of tocainide in canine acute myocardial infarction. We compared the effects of tocainide in infarcted and non-infarcted zones. The left anterior descending coronary artery of 8 dogs was ligated and bipolar ventricular electrograms were recorded from a needle electrode placed transmurally in the infarcted zone and from electrodes in the non-infarcted zone. Conduction intervals were measured from the onset of the limb lead QRS to the major deflection of the recorded electrograms in the infarcted and non-infarcted zones. Effective refractory periods were also determined. Measurements were made before, during and after intravenous infusion of tocainide in therapeutic doses 2 hours after infarct. Tocainide prolonged conduction intervals by 26-31% in the infarcted zone at peak (P less than 0.001), but by only 6% in the non-infarcted zone. Similarly, tocainide prolonged the effective refractory period by 27% (P less than 0.001) on the infarcted, but by 8% the non-infarcted zone. Tocainide had very slight effects on QRS duration. The present study shows that tocainide had selective effects in the infarcted zone on both conduction and effective refractory period. These selective effects may explain its antiarrhythmic effects in acute myocardial infarction.
 ...
PMID:Selective effects of tocainide in canine acute myocardial infarction. 211 May 52

Tocainide carbamoyl-O-beta-D-glucuronide, a major urinary metabolite of the antiarrhythmic drug tocainide [2-amino-N-(2',6'-xylyl)propanoxylidide], was isolated by preparative-TLC and preparative-HPLC. The isolated glucuronide was hydrolyzed in sodium hydroxide (pH greater than 12) to 3-(2',6'-xylyl)-5-methylhydantoin. This hydantoin product was also identified when tocainide was reacted with urea in urine. Structural characterization of the isolated tocainide glucuronide was carried out using GC-MS of the permethylated derivative. The molecular ion of the permethylated glucuronide was not observed, but ion fragments at m/z 232(244), 277(288), and 334(349) were found to correspond to the postulated novel carbamoyl ester structure of the permethylated (perdeuteromethylated) glucuronide. Structural evidence for the underivatized tocainide glucuronide was obtained using fast atom bombardment-MS. The [M + H]+ ion at m/z 413 was observed. Characteristic sodium ion adducts [M + Na]+ and [M-H + 2Na]+ were also observed at m/z 435 and 457, respectively.
 ...
PMID:Preparative high-performance liquid chromatography and preparative thin-layer chromatography isolation of tocainide carbamoyl-O-beta-D-glucuronide: structural characterization by gas chromatography-mass spectrometry and fast atom bombardment-mass spectrometry. 228 Mar 51

Surgical patients often are receiving antiarrhythmic therapy. Thus, because anaesthetic agents can affect cardiac function and may interact with concurrent antiarrhythmic medications, the anaesthetist should be aware of the electrophysiology associated with dysrhythmias and their management. Tocainide, flecainide, mexiletine, encainide and amiodarone have been introduced recently and each has an unique pattern of bioavailability, metabolism and toxicity. Patients treated with these drugs need special concern as they have abnormal cardiovascular systems and may be at increased risk for perioperative morbidity. In addition, unexpected untoward reactions and toxicity can result from interactions of anaesthetic agents and these drugs. This review discusses normal cardiac electrophysiology, common dysrhythmias and the electrophysiological effects of the newer oral antiarrhythmic drugs.
 ...
PMID:Advances in oral anti-arrhythmic therapy: implications for the anaesthetist. 240 52

The antiarrhythmic action of type I antiarrhythmic drugs may be mediated via binding of the drugs to a receptor associated with the cardiac sodium channel. This suggested that the effects of type I drugs might be stereospecific. We measured the effect of the tocainide stereoisomers (which have stereospecific antiarrhythmic effects) on conduction time and on radioligand binding to the cardiac sodium channel. The concentration-dependent effects of the individual enantiomers of tocainide on interventricular conduction time measured during constant rate ventricular pacing at 350 msec were assessed in 47 isolated perfused rabbit heart preparations. Significant increases (p less than 0.05) in conduction time occurred for both R-(-)-tocainide (75 microM, 10 +/- 5 msec) and S-(+)-tocainide (150 microM, 4 +/- 1 msec). R-(-)-Tocainide was more potent than the S-(+)-tocainide in prolonging conduction time (p less than 0.05). This stereospecific prolongation of conduction time suggested a stereospecific interaction with the sodium channel. The affinities of the enantiomers for the channel were measured with a radioligand binding assay using [3H]batrachotoxinin benzoate and freshly isolated cardiac myocytes. Both enantiomers inhibited [3H]batrachotoxin benzoate binding, but the IC50 (+/- SD) values were different: R-(-)-tocainide 184 +/- 8 microM; S-(+)-tocainide, 546 +/- 37 microM (p less than 0.003). Tocainide isomers are stereospecific in terms of prolonging conduction time and in binding to the sodium channel. The stereospecific electrophysiologic effects of tocainide may result from binding to a receptor associated with the cardiac sodium channel.
 ...
PMID:Stereospecific interaction of tocainide with the cardiac sodium channel. 245 Nov 17

A double-blind crossover study was performed in 20 patients to verify the efficacy of tocainide plus metoprolol in patients with premature ventricular contractions (PVCs) class Lown greater than or equal to 2 (mean frequency greater than or equal to 30/h) judged as being "stable" by at least three basal 24-h Holter ECGs with PVC variation of less than +/- 25%. All 20 patients were submitted to a placebo period; and all were subsequently randomized to therapy with tocainide 1800 mg/day or metoprolol 200 mg/day for 15 days and then to tocainide 1800 mg + metoprolol 200 mg/day or tocainide 1200 mg + metoprolol 200 mg/day for 15 days, followed by a crossover of the two combination treatments. At steady state in every stage we controlled for plasma levels of the drugs, a 24-h Holter recording, and a 12-lead ECG. A modified Lown score was evaluated together with the Lown class. Tocainide (mean plasma level 3.3 +/- 0.7 micrograms/ml) was efficacious in 3 of 8 patients, the modified Lown score decreased from 63 +/- 32 (placebo period) to 42 +/- 27 (p less than 0.01) and Lown 4B arrhythmias were abolished in 3 of 4 patients. Metoprolol (mean plasma level 97.4 +/- 89.6 ng/ml) was efficacious in 2 of 10 patients; the modified Lown score and Lown classes did not change significantly. Administration of tocainide 1200 mg + metoprolol 200 mg obtained a positive response in 9 of 12 patients, the modified Lown score decreased significantly compared with placebo (from 53 +/- 31 to 32 +/- 30, p less than 0.01) and Lown 4B arrhythmias were abolished in 2 of 5 cases. Tocainide 1800 mg plus metoprolol 200 mg was scarcely tolerated owing to neurologic and gastroenteric side effects, and only three patients completed this stage with no better antiarrhythmic results compared to the lower dose. In conclusion, the combination of tocainide at 1200 mg and metoprolol 200 mg is well tolerated, efficacious in a high percentage of patients, and superior to single drug therapy in patients with stable PVCs.
 ...
PMID:Tocainide and metoprolol: an efficacious therapeutic combination in the treatment of premature ventricular beats. 247 42


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>