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At least 19 recordsLinked to original sources
PubMed1976

[Comparative study, in the anesthetized dog, of the dromotropic effects of N-propyl ajmaline bitartrate, ajmaline hydrochloride and ajmaline monochloroacetate, by recording of His electrogram].

A-V and intraventricular conduction disturbances induced by 3 different salts of ajmaline: N-propyl ajmaline bitartrate (NPAB), hydrochloride (CHA) and mono chloro-acetate (MCAA), were studied by recording endocavitary His bundle activity in pentobarbital anesthetized dogs. Cumulative dose-response curves were obtained with 3 doses of each compound. The results demonstrate that: a) NPAB exerts a significant depressor effect (9 to 10 times more potent than CHA) on the following three conduction times: auriculo-Hisian, His-Pinkinje and Purkinje-ventricular; b) on His-Purkinje and intra ventricular conduction, MCAA exerts a weaker depressor effect than that of Nab. The lack of parallelism of dose-response curves prevents further comparative quantification; c) on atrio-hisian conduction, MCAA presents a delayed dose-related depressor effect suggesting the presence of an active metabolite. It is concluded that among ajmaline derivatives studied, Nab appears to be the most depressor on A-V and intraventricular conduction in the pentobarbital anesthetized dog.

Acetates↗
PubMed1982

[Cardiac toxicity of ajmaline. Comparison of acute voluntary poisoning with complications of the ajmaline test].

A comparative and retrospective study of 59 cases of acute voluntary self-poisoning observed at the Toxicology Department of Fernand Widal Hospital, and 15 cases of complications of the Ajmaline test observed in the Cardiology Department of Bichat Hospital showed a similarity in the cardiac effects of high dosage regardless of the mode of administration of the antiarrhythmic. Acute suicidal poisoning in adults or accidental poisoning in children caused toxic effects at doses over more than Ig: they are characterised by their sudden onset after a latent period of 1 to 2 hours and their short duration (no effects after the 12th hour). The ECG changes included:--First degree atrioventricular block (15 p. 100).--Intraventricular conduction defects were observed in almost all cases. They were proportional to the dose taken and were of prognostic interes (no cardiac arrests when the QRS remained less then 0,2 sec).--ST-T wave changes were observed in all patients. They lasted longer and were of no prognostic importance.--Extrasystoles and ventricular tachycardia are nearly always associated with poor hemodynamic tolerance (70 p. 100 of cardiac arrests, compared to only 16 p. 100 in this absence). This intoxication is serious with a mortality of 24 p. 100 of the reported cases and of 9 p. 100 of cases admitted to an Intensive Care Unit.--The complications of the Ajmaline test were similar, the time of apparition being a few minutes instead of a few hours. There were no deaths or serious hemodynamic complications in this series. This is without doubt related to the observation of the contraindications and the fractional administration of the Ajmaline. We conclude that oral Ajmaline, though well tolerated at therapeutic does may cause severe toxic overdose effects. Although its use remains justified in the treatment of arrhythmias, it should not be used for the symptomatic treatment of palpitations and neurovegetative imbalance.

Acute Disease↗
PubMed1977

Fluorescence data and studies on the lipid solubility and chemical structure of N-propyl-ajmaline as compared to ajmaline.

The quaternary N-propyl-ajmaline was found to have a higher lipid solubility than ajmaline. Lipid solubility was pH dependent. From chemical, fluorescence and IR-spectroscopic studies it is concluded that the existence of N-propyl-ajmaline in a tautomeric state between a carbinol-ammonium and an aldehyde-amine structure is responsible for the high lipid solubility.

Ajmaline↗
PubMed2000

The structure of the ring-opened N beta-propyl-ajmaline (Neo-Gilurytmal) at physiological pH is obviously responsible for its better absorption and bioavailability when compared with ajmaline (Gilurytmal).

Prajmaline, the semisynthetic propyl derivative of ajmaline, shows a much better bioavailability when compared with the Rauvolfia alkaloid ajmaline. Early NMR and IR-studies, fluorescence spectroscopic investigations and extraction experiments combined with ion-pair chromatography proved the thesis of a tautomeric equilibrium between an aldehyde-amine and a quaternary carbinol-ammonium component. The aim of this study was to confirm this thesis by HPLC-separation and by structure-determination of both tautomeric compounds.

Ajmaline↗
PubMed1975

Electrophysiologic effects of new ester of ajmaline 17-monochloroacetyl ajmaline hydrochloride (MCAA).

A new ajmaline ester, 17-monochloroacetyl ajmaline hydrochloride (MCAA) which has shown important clinical antiarrhythmic effects was studied in 20 isolated perfused rabbit hearts. Transmembrane potentials were recorded in atrial ventricular and A-V junctional fibers before and after perfusion of 3 mg/l of MCAA. There was a significant decrease in the action potential amplitude (81.1 plus or minus 6.0 to 75.2 plus or minus 5.8mV) overshoot (23.1 plus or minus 5.9 to 16.1 plus or minus 2.9mV) and maximum rate of depolarization (63.4 plus or minus 30.8 to 40.7 plus or minus 19.7 V/sec) and an increase in the action potential duration (119.8 plus or minus 12.6 to 135.6 plus or minus 25.1 msec). The strength interval curve was shifted to the right by MCAA. Conduction was increased in the atria and AV junction but not in the His-Purkinje system. MCAA appears to be a quinidine-like agent except for His-Purkinje conduction. This agent could offer important antiarrhythmic effects in atrial and ventricular arrhythmias.

Action Potentials↗
PubMed1983

Blockade of sodium and potassium channels in the node of Ranvier by ajmaline and N-propyl ajmaline.

The inhibition of sodium and potassium currents in frog myelinated fibres by ajmaline (AM) and its quaternary derivative, N-propyl ajmaline (NPA), depends on voltage-clamp pulses and the state of channel gating mechanisms. The permanently charged NPA and protonated AM interact only (or mainly) with open channels, while unprotonated AM affects preferently inactivated Na channels. Inhibition of Na currents by NPA and AM does not depend on the current direction and Na ion concentration in external or internal media. In contrast only the outward potassium currents can be blocked by NPA and AM; the inward potassium currents in high K+ ions external media are resistant to the blocking action of these drugs. The voltage dependence of ionic current inhibition by charged drugs suggests the location of their binding sites in the inner mouths of Na and K channels. Judging by the kinetics of current restoration after cessation of pulsing, the drug-binding site complex is much more stable in Na than in potassium channels. Batrachotoxin and aconitine, unlike veratridine and sea anemone toxin, decrease greatly the affinity of Na channel binding sites to NPA and AM. The effects of NPA and AM are compared with those of local anesthetics and other amine blocking drugs.

Aconitine↗
PubMed1975

Cardiovascular effects and blood concentrations of ajmaline and its 17-monochloroacetate ester in cats.

The antiarrhythmic drugs ajmaline and its 17-monochloroacetate ester (MCAA; Rtimos-Elle) were studied in cats. MCAA was less than half as toxic as ajmaline. Non-lethal doses of MCAA decreased blood pressure before heart rate, whereas ajmaline initially decreased heart rate. Both drugs prolonged the PR, QRS and QT intervals of the EKG. Recovery of these effects was within one hr. MCAA (10 mg/kg) and ajmaline (4.05 mg/kg) were studied separately by a one and 10 min infusion in the same cat. The dose of MCAA was ten times the usual dose in man and that of ajmaline four times the usual clinical dose. More marked effects were observed with the one min infusion. Arrhythmias were usually observed with ajmaline, but not with MCAA, even though it was rapidly converted to ajmaline. Maximal cardiovascular effects of MCAA and ajmaline were observed within 3 min of the end of infusion, which was also the time of peak blood levels. The elimination of MCAA resembled the kinetics of a multi-compartment system after a one min infusion. Peak blood levels declined by one-half in 3 min. Ajmaline blood levels declined linearly, with a half-life of 100 min, after a one min infusion. The peak blood level of MCAA after an intraduodenal dose of 25 mg/kg occurred at 20 min, whereas the peak blood level of the ajmaline formed occurred at 4 hr. In conclusion, MCAA has some different pharmacological properties and different kinetics of elimination than ajmaline.

Acetates↗
PubMed2001

Effects of ajmaline on rate-dependent atrioventricular node properties. Potential role in experimental atrioventricular re-entrant tachycardia.

Ajmaline is a well-known atrioventricular (AV) node depressant agent, but its effects on functional properties of the AV node and on experimental AV re-entrant tachycardia have not been explored. The aims of the present study were (1) to determine whether ajmaline administration modifies the rate-dependent properties of the AV node and (2) to correlate these changes with the actions of ajmaline on an in vitro model of AV re-entrant tachycardia. Selective stimulation protocols and mathematical formulations were used to quantify independently AV node recovery, facilitation, and fatigue in 10 isolated rabbit AV nodes. Ajmaline decreased facilitation and fatigue and had no significant effect on AV node recovery. The most important effect of ajmaline was rate-induced prolongation of AV node effective refractory period, resulting in a greater increase in tachycardia cycle length. AV re-entrant tachycardia was sustained when AV effective refractory period divided to tachycardia cycle length was less than 1, ajmaline suppressed AV re-entrant tachycardia by increasing the slope of the AV effective refractory period divided to tachycardia cycle length versus tachycardia rate relation, causing the critical ratio of 1 to be attained at a slower rate. A mathematical model incorporating quantitative descriptors of recovery, facilitation, and fatigue accounted for changes in nodal conduction time, AV effective refractory period, tachycardia cycle length, and AV effective refractory period divided to tachycardia cycle length under all conditions. It can be concluded that (1) ajmaline increases AV conduction time, decreases AV node fatigue, and facilitation, without altering AV node recovery. (2) Ajmaline significantly prolongs AV effective refractory period in a rate-dependent manner. (3) These changes play a role in ajmaline's actions on experimental AV re-entrant tachycardia. Ajmaline's ability to terminate re-entrant supraventricular tachycardia may be due, at least in part, to its ability to amplify the rate-induced prolongation of the nodal refractory period.

Action Potentials↗
PubMed1993

Dual inhibition of platelet-activating factor and arachidonic acid metabolism by ajmaline and effect on carrageenan-induced rat paw oedema.

The effects of ajmaline on human platelet aggregation, arachidonate metabolism and platelet activating factor (PAF)-induced lethality in rabbits were examined. Platelet aggregation induced by several stimuli (ADP, collagen, and PAF) was inhibited by increasing concentrations of ajmaline. The potency of ajmaline was higher when PAF was employed as stimulating agent in comparison with other agonists (IC50 70, 270 and 380 microM for PAF, ADP and collagen, respectively) whereas ajmaline had no effect against arachidonic acid-induced aggregation. In contrast however, ajmaline inhibited arachidonate metabolism by platelet homogenates. The formation of both thromboxane A2 and 12-hydroxy-eicosatetraenoic acid was inhibited by ajmaline with comparable potencies. Pretreatment of rabbits with ajmaline (50 mg kg-1) completely abolished the lethal effects of PAF (11 micrograms kg-1) given intravenously (P < 0.001). In addition, ajmaline at doses ranging from 50 to 100 mg kg-1 inhibited carrageenan-induced rat paw oedema (P < 0.001). In this test ajmaline was three times more potent than aspirin. In the light of these results we conclude that ajmaline, a known anti-arrhythmic agent is a PAF antagonist and a dual inhibitor of platelet cyclo-oxygenase and lipoxygenase enzymes with anti-inflammatory properties.

Ajmaline↗
PubMed1986

Mechanisms of pharmacokinetic interaction between ajmaline and quinidine in rats.

In order to elucidate the mechanism of ajmaline-quinidine interaction previously observed in humans, the effects of quinidine on pharmacokinetics of ajmaline were investigated in rats. Concurrent oral administration of 10 mg/kg of quinidine markedly increased the plasma concentration of ajmaline at a dose of 2 mg/kg. On the other hand, it did not affect the pharmacokinetics of ajmaline after intravenous dose. The availability of ajmaline after oral dose showed an increase from 13% to nearly 100% by the presence of quinidine, which suggests a change in the presystemic clearance of ajmaline. In fact, when ajmaline was administered into the intestinal loop, its concentration in mesenteric venous plasma increased approximately 5-fold by the combination with quinidine. Furthermore, quinidine delayed the elimination rate of ajmaline from the perfused rat liver. These results indicate that quinidine prevents presystemic elimination of ajmaline in the intestine and liver, and increases the systemic availability of ajmaline.

Ajmaline↗
PubMed1993

Effect of ajmaline on sustained ventricular tachycardia induced by programmed electrical stimulation in conscious dogs after myocardial infarction.

As yet the antiarrhythmic efficacy of ajmaline with regard to suppressing the induction of sustained ventricular tachycardia after myocardial infarction has not been determined. Therefore, programmed electrical stimulation was performed in 8 conscious, chronically instrumented mongrel dogs 8-20 days after a 4-hour occlusion of the left anterior descending coronary artery. At baseline all animals responded with sustained ventricular tachycardia. Thereafter, ajmaline was administered at two consecutive i.v. doses: a bolus of 0.7 mg kg-1 followed by infusion of 2 mg kg-1 h-1 and infusion of 4 mg kg-1 h-1. The induction of sustained ventricular tachycardia was prevented in 2/8 animals by 2 mg kg-1 h-1 ajmaline and in 1/8 animals by 4 mg kg-1 h-1 ajmaline. During sinus rhythm only 4 mg kg-1 h-1 ajmaline significantly increased QRS-duration and intraventricular activation times, but during rapid right ventricular pacing (cycle length = 330 ms) both doses of ajmaline increased QRS duration and intraventricular conduction times. 4 mg kg-1 h-1 ajmaline also increased the cycle length of induced sustained ventricular tachycardia. In 3 animals induction of sustained ventricular tachycardia during infusion of 4 mg kg-1 h-1 ajmaline was achieved by introduction of less extrastimuli than at baseline. Furthermore the coupling intervals of extrastimuli that induced sustained ventricular tachycardia were substantially prolonged by this dose. Inhomogeneity of conduction between left ventricular normal zone and left ventricular infarct zone was significantly increased by 4 mg kg-1 h-1 ajmaline during rapid right ventricular pacing, but not during sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Ajmaline↗