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Biomedical subjects

R Xhonneux

Publications and source records attributed to R Xhonneux.

At least 37 records · Page 2Linked to original sources
PubMed1981

Vascular effects of ketanserin (R 41 468), a novel antagonist of 5-HT2 serotonergic receptors.

The serotonergic receptor antagonist 3-(2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl)-2,4-[1H,3H]quinazolinedione Ketanserin (R 41 468) caused a dose-dependent inhibition on the contractile responses to 5-hydroxytryptamine of isolated rat caudal artery, canine basilar, carotid, coronary and gastrosplenic arteries, canine gastrosplenic veins (threshold 10(-10)-10(-9) M) and canine saphenous veins (threshold 10(-8) M). In concentrations up to 2.5 X 10(-5) M, it did not have agonistic properties. From 10(-8) M on, R 41 468 inhibited the contractions of rat caudal arteries and canine saphenous veins caused by postjunctional alpha adrenergic activation. In the rat caudal artery, R 41 468, in concentrations which did not affect the contractile response to norepinephrine, abolished the amplifying effect of low concentrations of 5-hydroxytryptamine on alpha adrenergic activation. In the canine saphenous vein, R 41 468 did not affect the prejunctional inhibitory effect of 5-hydroxytryptamine during sympathetic nerve stimulation. In the perfused guinea-pig stomach, R 41 468 depressed and in certain experiments reversed the vasoconstrictor response to 5-hydroxytryptamine. In isolated perfused kidneys from both normotensive and spontaneously hypertensive rats, R 41 468, in concentrations which did not depress vasoconstrictor responses to exogenous norepinephrine, inhibited those to 5-hydroxytryptamine. The compound caused a dose-related reduction in aortic blood pressure in unanesthetized spontaneously hypertensive rats, which was larger and occurred at lower concentrations, than in control animals. These results demonstrate that R 41 468 is a potent antagonist of the vasoconstrictor effects of 5-hydroxytryptamine, in particular of its amplifying effect on threshold amounts of norepinephrine, which may help explain its antihypertensive properties.

Adrenergic alpha-Agonists↗
PubMed1981

Lorcainide (R 15 889), a first review.

This is a first review of lorcainide hydrochloride, a new antiarrhythmic agent with local anaesthetic activity. The antiarrhythmic actions of lorcainide are mediated by an impairment of fast sodium conductance. Pharmacologically, this drug appears effective in suppressing reentry phenomena and ectopic pacemaker activity, especially in the ventricles. Lorcainide has only negligible depressant effects on important haemodynamic parameters and its toxicity is minimal. The drug is well absorbed by the oral route and its elimination half-life is long when compared with other substances. Lorcainide-induced QRS widening is directly correlated with the plasma levels of the drug. Preliminary experience in supraventricular arrhythmias is promising but pre-excitation syndromes and the ventricular arrhythmias are the main indications for this drug since a very high response rate has been observed in these conditions. Side effects are harmless and dose-dependent, but may be clinically troublesome.

Absorption↗
PubMed1979

Comparative study of cardiovascular, neurological and metabolic side effects of 8 narcotics in dogs. Pethidine, piritramide, morphine, phenoperidine, fentanyl, R 39 209, sufentanil, R 34 995. III. Comparative study of the acute metabolic toxicity of the narcotics used in high and massive doses in curarised and mechanically ventilated dogs.

The I.V. administration in dogs of high and massive doses of narcotics produced an acute rise in CO2 consumption, a rise of plasma catecholamines and other slight biochemical and metabolic perturbances. A general trend towards metabolic acidosis and hypermetabolism was noticed but important differences appeared according the drugs and doses chosen. The safety margin for metabolic toxicity (ratio between IV doses producing severe metabolic side-effects and doses necessary for deep surgical analgesia) were calculated for each narcotic and found as follows: 1 for pethidine, 3.3 for piritramide, 13 for morphine and phenoperidine, 12.5 for R 39 209, 60 for fentanyl, 800 for sufentanil and 4 000 for R 34 995. Drug associations may decrease or increase the metabolic safety margin of the narcotics. Beneficial associations with morphinomimetics are found with droperidol, etomidate and flunitrazepam.

Acidosis↗
PubMed1979

Comparative study of cardiovascular, neurological and metabolic side effects of 8 narcotics in dogs. Pethidine, piritramide, morphine, phenoperidine, fentanyl, R 39 209, sufentanil, R 34 995. II. Comparative study on the epileptoid activity of the narcotics used in high and massive doses in curarised and mechanically ventilated dogs.

The experimental design, described in part I, was again used here. The electrocortical activity was registered with an EEG amplifier using a bipolar derivation of needle electrodes fixed in the scalp of a dog in the fronto-occipital position. In this situation the convlusion threshold for the 8 substances is as follows: pethidine 20 mg.kg-1 I.V., piritramide 30, morphine 180, phenoperidine 4, R 39 209 5, fentanyl 4, sufentanil 4 and R 34 995 10 mg.kg-1 I.V. Comparing the I.V. doses producing severe convulsions with the doses necessary for deep surgical analgesia a safety margin of neurological toxicity was calculated. This was for pethidine 2.2, for piritramide 6.6, for phenoperidine 16, for R 39 209 62.5, for morphine 72, for fentanyl 160, for sufentanil 1 000 and for R 34 995 10 000. It is concluded that for pure narcotics there exists an inverse relationship between analgesic potency and neurological toxicity which is always accompanied by a hyperactivity of the automatic nervous system. Factors modifying the convulsive level of the narcotics are still under investigation. In the meanwhile it can be stated that the association of a strong narcotic with flunitrazepam, droperidol or etomidate will increase the convulsion threshold of the morphinomimetics.

Acidosis↗
PubMed1978

Preliminary data on antiserotonin effects of oxatomide, a novel anti-allergic compound.

Oxatomide or R 35443, 1-(3-[4-(diphenylmethyl)-1-piperazinyl]propyl)-1,3-dihydro--2H-benzimidazol-2-one, a compound with potent antihistaminic and anti-anaphylactic activities, shows specific antiserotonin effects on isolated caudal arteries of the rat. In vivo it is a powerful antagonist of bronchospasm induced by serotonin and by histamine; it has no anticholinergic effects and does not affect blood pressure in spontaneously hypertensive rats. These antiserotonin properties of oxatomide may contribute significantly to its anti-allergic activity.

Animals↗
PubMed1978

Antiarrhythmic, electrophysiologic and hemodynamic effects of lorcainide.

Lorcainide hydrochloride or N-(4-chlorophenyl)-N-[1-(1-methyl-ethyl)-4-piperidinyl]benzeneacetamide mono-hydrochloride (R 15889) is a new anti-arrhythmic drug. Studies in dogs show that lorcainide is effective against post-infarction and ouabain-induced ventricular arrhythmias, and abolishes acetylcholine and aconitine-induced atrial fibrillation; it elevates the threshold of electrically induced ventricular fibrillation. In isolated dog and cow Purkinje fibers, in dog ventricular and in guinea-pig auricular muscle preparations, lorcainide decreases the rate of rise of the transmembrane action potential, the conduction velocity and spontaneous activity. It prolongs the refractory period of isolated Purkpinje and ventricular muscle preparations, and the functional refractory period of the AV node in the guinea-pig heart. It has no effect on Ca mediated electrical activity. Isometric force measurements in isolated cat papillary muscles and hemodynamic studies in anaesthetized and unanaesthetized dogs indicate that lorcainide moderately decreases myocardial contractility. Side effects observed at large doses are of central origin and include salivation, tremor and vomiting. Intravenous injection induces transient peripheral vasodilatation. Lorcainide is an antiarrhythmic of the local anaesthetic type. It is characterized by a good oral absorption, a long duration of action and a large safety factor.

Acetamides↗
PubMed1978

Effect of lorcainide, a new antiarrhythmic compound, on the changes in heart rhythm induced by intravenous injection of adenosine-5'-diphosphate in rats.

In rats, the intravenous injection of 1 mg/kg A.D.P. (adenosine-5'-diphosphate) results in transient thrombocytopenia, bradycardia and arrhythmias. Pre-treatment of the animals with the antiarrhythmic compounds lorcainide, aprindine, procaine (1.25, 2.5, 5 mg/kg i.v.) and xylocaine (5, 10, 20 mg/kg i.v.) before A.D.P. injection results in a reduction of bradycardia and a faster normalization of heart rate. All 4 compounds were equipotent in this respect, but the higher dose of xylocaine used should be stressed. The duration of irregular heart rhythm after A.D.P. injection was significantly shortened by all 4 compounds. Peak thrombocytopenia after A.D.P. administration is reduced only by lorcainide and the highest dose of aprindine, with two dose levels of xylocaine, but is not reduced by procaine. Suloctidyl (50 mg/kg orally) had no effect on any of the parameters registered. From this study we conclude that the normalization by the compounds of cardiac rate and rhythm disturbances after A.D.P. is due to their direct antiarrhythmic effect rather than to inhibition of platelet aggregation.

Acetamides↗
PubMed1976

Electrophysiological effects of droperidol in different cardiac tissues.

The effect of droperidol in concentrations between 0.05 and 5 mg/I was evaluated on different electrophysiological variables in auricular preparations of the guinea-pig, papillary muscles of dog and cat, Purkinje fibres of the dog, cow and sheep. At low concentration (0.25 to 0.5mg/I) droperidol decreased pacemaker activity and prolonged the effective refractroy period. The inhibition of pacemaker activity was not accompanied by a reduction in the rate of early diastolic depolarization, but was related to an inhibition of the depolarization process during late diastole. At high concentrations (5mg/I) resting potential, action potential amplitude, (dV/dt)max and conduction velocity were reduced. Reduction of dV/dt during the upstroke was more pronounced at lower membrane potentials, the inactivation curve was shifted to more negative membrane potentials. The action potential was lengthened or shortened, the effect being dependent on the frequency, dose, exposure time and animal species. Droperidol had no deleterious effect on Ca-mediated action potentials. The antiarrhythmic activity of droperidol in therapeutic concentrations (0.25 and 0.5mg/I) can be explained by the reduction of pacemaker activity and the lengthening of the effective refractory period. In terms of changes in ion conductance most effects can be explained by a reduction in Na conductance. No simple explanation can be offered for the complex changes in action potential duration.

Action Potentials↗
PubMed1975

Lidoplazine and Na and K distribution in normo-and hypokalaemic rats.

The effects of lidoplazine on K-metabolism were investigated in two types of experiments. (1) K and Na concentrations were measured in plasma, heart, diaphragm and erythrocytes in normo- and hypokalaemic rats with or without chronic (1 month) lidoplazine treatment. Total body weight, heart weight, dry weight/wet weight ratios and extracellular space were also determined. (2) Radioactive K influx in the heart was measured in acute in vitro experiments with or without lidoplazine. It is demonstrated that while lidoflazine has no effect on the Na and K distribution of normokalaemic animals, it has rather a K-saving effect in conditions of severe loss of intra- and extracellular K-ions. In normal in vitro preparations the unidirectional K-influx is not affected by lidoflazine.

Animals↗