ajmaline and detajmium

The objective of this study was to develop a very sensitive and selective method for the determination of detajmium (4-3-diethylamino-2-hydroxypropyl-ajmaline), a sodium-channel-blocking drug with antiarrhythmic properties, in serum. A high-performance liquid chromatography (HPLC) method with solid-phase extraction and fluorimetric detection has been applied. Serum samples were diluted with phosphate buffer (pH 3.5) and the extraction of detajmium and ajmaline, which was used as an internal standard, was carried out with Oasis cartridges (Waters). The chromatographic separation was performed on a RP18 column. The limit of quantification for serum samples of detajmium was 1 ng/ml with good reproducibility (R.S.D. < 15%) and a linear response from 1 to 200 ng/ml. The described method is highly sensitive and specific for the determination of detajmium in serum of patients and volunteers.

Topics: Ajmaline; Anti-Arrhythmia Agents; Chromatography, High Pressure Liquid; Reference Standards; Reproducibility of Results; Sensitivity and Specificity; Spectrometry, Fluorescence

In a case report, a Tachmalcor intoxication with a dose of 18 mg/kg body weight is described. This dose caused a ventricular flutter in the patient which lasted for a total of 10 hours, despite intensive treatment. The treatment began approximately three hours after the intoxication and concentrated on therapy of the ventricular tachycardia. The use of Xylocitin 2%, defibrillation, glucagon and sodium chloride is recommended with such symptoms. Additionally, we used hemoperfusion for drug elimination. Despite the cardiac rhythm disorder of such duration, no neurological deficiencies were observed in the patient. Intoxications caused by these drugs in normal intensive therapies are extremely rare and for this reason treatment can often be very problematic. The following article reports on the successful therapy of one such patient.

Topics: Adult; Ajmaline; Anti-Arrhythmia Agents; Critical Care; Dose-Response Relationship, Drug; Drug Overdose; Heart Arrest; Humans; Suicide, Attempted

Detajmium (4--3'-diethylamino-2'-hydroxypropyl--ajmalin) is an Na(+)-channel-blocking drug with an extremely long recovery from use-dependent sodium channel block. The aim of the present study was to investigate the rate-dependent effects of detajmium on the intraventricular conduction of isolated, spontaneously beating, guinea pig hearts in comparison with the effects of propafenone. Detajmium (0.3 microM) and propafenone (0.3 microM) caused comparable prolongations of the intraventricular conduction time during sinus rhythm. The time to steady state of the rate-dependent QRS prolongation during rapid ventricular pacing follows an exponential function of the beat number after an abrupt change of frequency and is characterized by a drug-specific time constant. This time constant was significantly longer for detajmium (tau = 265 +/- 165 beats; mean +/- SEM; n = 6) than for propafenone (tau = 31 +/- 4 beats; n = 11; p < 0.01). In the presence of propafenone, QRS duration peaked initially before decreasing to a steady state. Detajmium, in contrast, progressively broadened the QRS complex. Both substances caused the greatest increase in the ventricular effective refractory period (V-ERP) when the number of conditioning stimuli (interstimulus interval, 120 ms) was in the range of the time constant. However, when the number of conditioning stimuli was further increased, the V-ERP for propafenone diminished progressively. In conclusion, propafenone displayed, in comparison with detajmium, only a transient rate-dependent effect on intraventricular conduction and V-ERP.

Topics: Ajmaline; Animals; Anti-Arrhythmia Agents; Female; Guinea Pigs; Heart Conduction System; Heart Rate; Heart Ventricles; Male; Propafenone

We studied the electrophysiologic effects of the antiarrhythmic compound detajmium (Tachmalcor) on isolated dog and rabbit cardiac preparations, applying the conventional intracellular microelectrode techniques. In dog ventricular muscle fibers (37 degrees C, stimulation frequency 1 Hz), 1 microM detajmium did not change resting potential (RP), action potential amplitude (APA), AP duration measured at 90% of repolarization (APD90), or effective refractory period (ERP) significantly, but reduced maximum rate of depolarization (Vmax) significantly from 236.7 +/- 28.9 to 177.3 +/- 22.5 V/s (n = 6, p < 0.01). In dog Purkinje fibers (37 degrees C, stimulation frequency 1 Hz), 1 microM detajmium significantly decreased APA from 111.1 +/- 12.3 to 100.0 +/- 2.5 mV (n = 8, p < 0.003), APD90 from 359.0 +/- 17.5 to 262.1 +/- 12.3 ms (n = 8, p < 0.001) and Vmax from 687.5 +/- 57.2 to 523.7 +/- 58.2 V/s (n = 8, p < 0.001) without changing maximal diastolic potential or ERP/APD ratio significantly. The effect of detajmium on Vmax in both dog ventricular muscle and Purkinje fibers was frequency dependent. Fractional Vmax block was 0.185 +/- 0.008 1/AP. The recovery kinetics of Vmax (offset kinetics) was extremely slow (time constant = 348.16 +/- 57.43 s) considerably slower than most of those of other antiarrhythmic drugs yet reported. Detajmium in concentration < 32 microM did not influence the beta-adrenoceptors or slow response APs in dog ventricular tissue significantly. On the basis of its electrophysiologic effects, detajmium, like prajmaline, encainide, or flecainide, can be best classified as a class I/C antiarrhythmic drug according to the Vaughan Williams' classification scheme.

Topics: Action Potentials; Ajmaline; Animals; Anti-Arrhythmia Agents; Dogs; Electrophysiology; Female; Heart; Heart Ventricles; In Vitro Techniques; Male; Microelectrodes; Purkinje Fibers; Rabbits; Receptors, Adrenergic, beta; Ventricular Function

After ingestion of an unknown dose of detajmium, a 14-year-old female collapsed with asystolia. Resuscitation efforts were not successful. A medicolegal autopsy was carried out, and blood, liver and gastric content were extracted and analyzed by gas chromatography-mass spectrometry (GC-MS). After derivatization with acetic anhydride, detajmium and twelve of its derivatives and metabolites were identified. The main metabolic pathways include hydroxylation and subsequent O-methylation of the indol ring, and oxidation as well as reduction of the C-21 hydroxyl function. Cleavage of the N-alkyl side-chain is a further, possibly non-enzymatic degradation pathway. Artifact formation induced by acetylation included dehydratation of the hydroxyl function of C-21 and the N-alkyl side-chain. The detajmium concentration in blood of the decreased was determined by high-performance liquid chromatography with fluorimetric detection (12 micrograms/ml).

Topics: Acetic Anhydrides; Adolescent; Ajmaline; Anti-Arrhythmia Agents; Autopsy; Chromatography, High Pressure Liquid; Female; Gas Chromatography-Mass Spectrometry; Gastrointestinal Contents; Humans; Liver

Topics: Adult; Ajmaline; Combined Modality Therapy; Dose-Response Relationship, Drug; Electrocardiography; Female; Heart Block; Humans; Lidocaine; Suicide, Attempted; Ventricular Fibrillation

On 31 inpatients with ventricular permanent extrasystoles (12 females, 19 males) at the age of 17--17 years altogether 45 oral experiments of rhythmisation were performed, on them 29 times with the ajmalium derivate detajmium bitartrate (Tachmalcor) and 16 times with ajmalin (Tachmalin). In 14 cases the comparison of the effect of the two substances was performed in the intraindividual test. In ventricular extrasystoles the ajmalin derivation compared with the initial substance was significantly more effective antiarrhythmically already when the half dose was used. However, it led at the same time to a greater retardation of the intracardiac stimulus conduction. Heart rate and blood pressure were influenced only at the beginning of the treatment and only unessentially. The subjective tolerability was very good. In 9 cases with oral ambulatory long-term treatment the daily maintenance doses of 75--100 mg detajmium bitartrate proved to be fully effective in therapeutic respect. Practical therapeutic conclusions are derived from the results obtained.

Topics: Administration, Oral; Adolescent; Adult; Aged; Ajmaline; Anti-Arrhythmia Agents; Cardiac Complexes, Premature; Dose-Response Relationship, Drug; Electrocardiography; Female; Heart Rate; Heart Ventricles; Humans; Long-Term Care; Male; Middle Aged

Topics: Ajmaline; Anti-Arrhythmia Agents; Child, Preschool; Humans; Infant; Male