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Query: CAS:41708-72-9 (Tocainide)
 93 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antiarrhythmic effect of tocainide, an amine analogue of lidocaine, was tested in the course of a double-blind trial on 12 patients with ventricular arrhythmias. Daily dose was 400 or 600 mg every eight hours. In all tested patients the frequency of ventricular extrasystoles, analysed by means of ambulatory 24-hour ECG monitoring, decreased by an average of 70%. In four of nine patients the severity of the ventricular extrasystoles (Lown's classification) was improved by at least one functional class. There was no correlation between the anti-arrhythmic effect and the plasma level of tocainide, which was between 4.1 and 9.7 micrograms/ml. Four patients had side effects in the form of CNS symptoms, but the drug did not have to be discontinued. Tocainide is an orally effective antiarrhythmic drug, an alternative in the treatment of ventricular arrhythmias.
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PMID:[Anti-arrhythmic effect of tocainide (lidocaine congener) on ventricular arrhythmias (author's transl)]. 9 43

To characterize the acute hemodynamic effects of tocainide hydrochloride, a new antiarrhythmic agent, 11 patients undergoing diagnostic cardiac catheterization were given intravenous infusions of the drug for 15 minutes at rates of 0.50 (six patients) or 0.75 (five patients) mg/kg/min. The hemodynamic status of these subjects was determined before, during, and for 15 minutes after treatment, and blood levels of tocainide were followed during and after treatment. Tocainide blood levels at the end of the infusions were 14.9 +/- 1.6 microgram/ml (S.E.) and 15 minutes later were 6.0 +/- 0.7 microgram/ml. In these subjects treatment was not associated with significant changes in Ao or PCW, but it was associated with a statistically significant but small decrease in LV dp/dt. At the same time, LVED was not significantly elevated. Treatment was also accompanied by small increases in PA diastolic and mean pressures, but RA and RV were unchanged. Significant changes were not seen in HR, CO, CI, SV, SVR, or PVR. Thus, the intravenous infusion of 0.50 and 0.75 mg/kg/min of tocainide for 15 minutes produced small but statistically significant depression of left ventricular function without producing changes in CO or clinical evidence of congestive heart failure.
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PMID:Acute hemodynamic effects of tocainide in patients undergoing cardiac catheterization. 37 Jan 55

The effects of the lidocaine derivative 2-amino-2',6'-propionoxylidide hydrochloride (tocainide, W-36095) on the contraction force and on membrane resting and action potentials of rat diaphragm were tested in vitro. In a concentration of 5 x 10(-4) mol/l, tocainide reduced the amplitude of the twitch by about 25% within 15 min. This reduction was reversible on washout of the drug. Tocainide had little effect on the membrane resting potential, but considerably affected the action potential: rate of rise, maximum amplitude and rate of fall were reduced, the duration increased. The conduction velocity of the action potential was reduced by 20%. Experimental myotonia produced in excised diaphragms or in anesthetized whole animals by anthracene-9-carboxylic acid was completely abolished by low doses of tocainide.
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PMID:Effects of tocainide on normal and myotonic mammalian skeletal muscle. 58 39

In order to evaluate its hemodynamic actions, tocainide, a new orally effective antiarrhythmic drug, was given intravenously over a 15 minute period to 12 patients with compensated left ventricular dysfunction. Doses were 0.5 (4 patients) or 0.75 (8 patients) mg/kg/min. Hemodynamics and drug plasma concentrations were measured at the end and 15 minutes after the end of the infusion. Tocainide infusion produced small but statistically significant increases in the pulmonary and systemic vascular resistance, aortic and pulmonary arterial pressure, and left and right ventricular end-diastolic pressure. There was no significant change in left ventricular dp/dt, heart rate, or cardiac index. In patients with compensated left ventricular dysfunction, tocainide produces a small rise in vascular resistance and arterial pressure. Overall cardiac function is maintained with a small increase in left ventricular end-diastolic pressure.
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PMID:The hemodynamic effects of intravenous tocainide in patients with heart disease. 63 Jun 89

Long-term tocainide therapy has been evaluated in 17 patients with ventricular arrhythmias. Ventricular tachycardia and/or fibrillation was recurrent and sustained in nine patients, and symptomatic but unsustained in three others. Five patients had frequent but only mildly symptomatic ventricular irritability. In all patients, arrhythmias could not be managed with quinidine, procainamide or propranolol. Tocainide doses ranged from 300 to 700 mg every 8 hours (mean steady-state plasma concentrations ranged from 5.75 to 12.18 microgram/ml). Tocainide therapy was unsuccessful in eight patients; three died during therapy and five had no antiarrhythmic response. The data suggest that evaluation of long-term drug efficacy, using the criterion of reduction of asymptomatic arrhythmias, is best documented by multiple sequential ambulatory electrocardiographic recordings, both on and off the drug. Tocainide controlled arrhythmias in nine patients (53%), with criteria of success being continued reduction of ectopic beats and/or control of symptomatic recurrences. Seven patients remain on therapy. Side effects generally have been minor and well-tolerated.
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PMID:Long-term tocainide therapy for ventricular arrhythmias. 63

Tocainide is a new antiarrhythmic drug with a chemical structure related to that of lidocaine. In the present study, healthy volunteers were investigated after infusion of tocainide 450 mg over 45 min. In nine subjects His bundle electrograms, sinus recovery time and ventricular effective refractory periods were recorded. No major changes were seen. In eight cases the hemodynamic effects at rest and during exercise were studied. No significant circulatory effects were observed. No clinically important side-effects were noted.
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PMID:Electrocardiographic and hemodynamic effects of tocainide (W-36095) in man. 72 2

Tocainide, a new oral antiarrhythmic agent, was studied in man in a short-term protocol designed to evaluate the efficacy, kinetics, and toxicity of this compound. Premature ventricular contractions (PVCs) were suppressed by less than 70% in 11 of 15 patients compared with pre-drug placebo controls. For these 11 responders, there was an average PVC reduction of 91% +/- 10 (range 70 to 100%) at tocainide doses not associated with side effects. Mild transient central nervous system toxicity was observed in some patients near the time of peak concentrations during the highest dose administered. The drug was found to have linear kinetics over the dose range studied and a plasma half-life of 13.5 +/- 2 hours. Plasma concentration-response curves indicate antiarrhythmic activity over all plasma concentrations, with 70% PVC reduction above 6.0 mug/ml. This study suggests that tocainide is a safe and effective antiarrhythmic agent during short-term administration and is worthy of further clinical trials.
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PMID:Clinical efficacy and pharmacokinetics of a new orally effective antiarrhythmic, tocainide. 79 36

A sensitive and specific method is described for the determination of a new primary aliphatic amine antiarrhythmic drug, tocainide. Tocainide, together with an internal standard, is selectively extracted from plasma or blood and reacted with dansyl chloride. The highly fluorescent dansyl derivatives are separated using high-pressure liquid chromatography and measured using a fluorescence detector. The method can measure therapeutic and subtherapeutic concentrations of the drug (0.1-5.0 microng/ml of plasma) with a standard deviation of less than 2%.
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PMID:High-pressure liquid chromatographic analysis of drugs in biological fluids II: determination of an antiarrhythmic drug, tocainide, as its dansyl derivative using a fluorescence detector. 85 79

Tocainide, a primary amine analogue of lidocaine, is effective against some experimental and clinical arrhythmias. Its pharmacokinetic behavior was studied in 6 healthy male subjects. Peak blood levels (CB max) and area under the blood concentration-time curve (AUC) were linearly related to dose with slopes of 0.0067 mcg/ml and 6 min mcg/ml per milligram of dose, respectively. Renal clearance of tocainide averaged 59 ml/min when urinary pH was uncontrolled or acidified, while it was reduced to 13 ml/min during intense sodium bicarbonate loading. Blood levels following intravenous infusion were well described by a 2-compartment open model with a volume of the central compartment of 0.92 L/kg. The t 1/2 beta was 11 hr and total body clearance was 166 ml/min. Loo-Riegelman analysis of the absorption rate did not allow unequivocal assignment of an "order" to the absorption process. Bioavailability approached 100%. Administration of drug 5 min after a test meal suppressed CB max 40% but minimally affected AUC. Approximately 50% of the drug was found to be plasma protein bound at clinically effective concentrations.
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PMID:Kinetics of the oral antiarrhythmic lidocaine congener, tocainide. 126 16

In the present study we examined the effect of systemic tocainide on sensory hypersensitivity in rats after spinal cord ischemia induced by a photochemical technique. After induction of spinal cord ischemia the rats exhibited a sensory disturbance which was mainly expressed as vocalization to innocuous cutaneous mechanical stimuli (allodynia) in the flank area during the following several days. Tocainide at 75 mg/kg i.p., but not 50 mg/kg i.p., significantly increased the vocalization threshold to mechanical pressure for 2 h. The effect of intraarterial (i.a.) tocainide on the responses of dorsal horn wide-dynamic-range (WDR) neurons to suprathreshold electrical stimulation of their receptive fields was also examined in normal rats and after transient spinal cord ischemia, at a time when the animals exhibited typical behavioral allodynia in the dermatomes innervated by the ischemic spinal segments. In normal rats, tocainide (50 mg/kg i.a.) strongly suppressed the responses of WDR neurons to C fiber input with lesser effect on A fiber input. In allodynic rats, tocainide suppressed the augmented A and C fiber mediated responses of WDR neurons to the extent that their responses were similar to those seen in normal rats without tocainide. There was no difference in the overall depression of A and C fiber mediated input by tocainide between normal and allodynic rats. The present results demonstrated the analgesic effect of systemic tocainide in relieving allodynia in rats and indicated that systemic local anesthetics, at doses that do not block nerve conduction, can be effective in suppressing dorsal horn WDR neuronal activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Systemic tocainide relieves mechanical hypersensitivity and normalizes the responses of hyperexcitable dorsal horn wide-dynamic-range neurons after transient spinal cord ischemia in rats. 145 25


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