Trimetazidine in the myocardial cell mechanisms of cytoprotection.

The experimental results demonstrate that TMZ displays the pharmacological characteristics of a "cytoprotective agent", since this drug exerts an anti-ischemic effect on myocardium totally independent of any hemodynamic changes.

A lymphatic function of Daflon 500 mg.

Unlabelled: The lymphagogue activity of a micronized, purified flavonoidic fraction, Daflon 500 mg (D) (diosmin 90%+ hesperidin 10%) was tested in dogs and rats.

Methods: In the anaesthetized mongrel dog measurement of lymphatic flow was carried out in a thoracic duct fistula inserted 30 min prior to I.V.

Pharmacologic properties of Daflon 500 mg.

Aims And Methods: Some pharmacologic activities of a micronized flavonoid complex consisting of 90% diosmin + 10% hesperidin (Daflon 500 mg*) have been investigated by use of various experimental models: (1) interference with mechanisms of edema (synthesis of arachidonic acid derivatives, microvascular hyperpermeability induced by bradykinin, ischemia, or streptozotocin), (2) interference with lymphatic drainage (thoracic duct fistula in the dog).

Results: Daflon 500 mg inhibited prostaglandin E2 (PGE2) and thromboxane A2 (TxA2) synthesis during a one-month oral daily treatment (100 mg.kg-1.

Neurochemical and pharmacological properties of tianeptine, a novel antidepressant.

Tianeptine is a tricyclic antidepressant with an unusual chemical structure (a long lateral chain grafted on to a substituted dibenzothiazepin nucleus), and with biochemical and animal-behavioural properties which are strikingly different from those of classical tricyclics. Unlike the latter, which decrease serotonin (5-HT) uptake, acute and chronic tianeptine treatment enhances 5-HT uptake in rat brain and in rat and human platelets ex vivo. In vivo, tianeptine potentiates the depletion of rat brain 5-HT by 4-methyl-alpha-ethyl metatyramine and increases rat hippocampal 5-HIAA; 5-HT uptake inhibitors (e.

Daflon as a cellular antioxidant and a membrane-stabilizing agent in human fibroblasts irradiated by ultraviolet A radiation.

Daflon is a strong inhibitor of Cu(2+)-induced arachidonic acid peroxidation, as revealed by the inhibition of thiobarbituric acid-reactive substance formation in mixed liposomes of phosphatidylcholine and arachidonic acid. Diosmin, the major Daflon constituent, is a good complexant of Cu2+ ions but not of Fe2+ ions. The Cu2+ complex formation may thus explain part of the antioxidant effect.

Structure-activity relationships as a response to the pharmacological differences in beta-receptor ligands.

With a few notable exceptions, beta-receptor ligands (agonists and antagonists) belong to the aryl- or heteroaryl-ethanolamine series and to the aryl- or heteroaryl-oxypropanolamine series. Structure-activity relationships for beta-adrenergic agonists show that a secondary amine in the phenylethanolamine side chain ending is essential for receptor stimulation. The 3,4-dihydroxyphenyl groups may be replaced by "phenol equivalents" (-CH2OH, -NHCONH2, -CHOH, -NHSO2CH3).

[Tianeptine, an uncommon psychotropic drug].

The pharmacological studies show that tianeptine (Stablon) is an original psychotropic drug. In classical and behavioural pharmacology, tianeptine has a novel antidepressant profile, different from other molecules and an anxiolytic effect but different from the benzodiazepines. Tianeptine does not cause sedation and sleeping troubles.

Cardiovascular and central nervous system effects of rilmenidine (S 3341) in rats.

Rilmenidine (S 3341) is a new alpha 2 agonist, with antihypertensive properties. Pharmacologic data concerning its hemodynamic and central nervous system effects in the rat are described in this report. In the anesthetized or conscious spontaneously hypertensive rat, rilmenidine was found effective and potent as an antihypertensive agent, lowering blood pressure in a dose-dependent manner after intravenous and oral administration.

Structure-activity relationships of tricyclic antidepressants, with special reference to tianeptine.

Structure-activity relationships in the classical antidepressant (imipramine-like) series show a relative lack of specificities: Compounds should simply have a nucleus consisting of two phenyl rings and a third, seven-member central ring. This central ring may have one, several, or no heteroatoms, and it may or may not be saturated. The side chain may be attached to any one of the atoms of the central ring, but it must be short (two or three carbon atoms), and have a terminal amine group (secondary, tertiary, or included in a ring).

Effect of chronic treatment with a purified flavonoid fraction on inflammatory granuloma in the rat. Study of prostaglandin E2 and F2 alpha and thromboxane B2 release and histological changes.

S-5682 (Daflon-500 mg), a purified flavonoid fraction, consisting of 90% diosmin (a flavone derivative) and 10% hesperidin (a flavanone derivative), was administered to rats by intubation in the daily dose of 100 mg/d. 15 days after the start of treatment, polyurethane sponges were implanted in the subcutaneous connective tissue in the dorsolumbar region under rapid ether anaesthesia. Similar fragments of sponge were implanted in a group of control animals who received the vehicle (saccharose syrup) only, also by the oral route.

[Cellular disorders induced by ischemia. The effect of trimetazidine].

In contrast with the classical anti-anginal drugs, trimetazidine appears to be a very specific treatment, especially to the ischaemic cell. Whereas beta-blockers, nitrates and calcium antagonists all act outside the real ischaemic area (on peripheral veins or arteries, coronary vessels, whole heart muscle contractility, sinus node, endo-epicardial blood flow ratio, etc..

[The almitrine dimesylate molecule. Various structure-activity relationship aspects].

The improvement in PaO2 induced by almitrine bismesylate is due to better adjustment between alveolar ventilation and lung perfusion (VA/Q ratio). Experimental studies and clinical pharmacology suggest that this improvement involves changes in both alveolar ventilation and pulmonary circulation. By synthesizing and testing compounds with different structures in a series of trisubstituted triazines, it has been possible to determine qualitative structure-activity relationships and to select almitrine bismesylate is due to better adjustment between the greatest, most rapid and longest lasting increase in PaO2.

Electrophysiologic effects of bepridil in the anesthetized dog studied by endocardiac electrodes.

The electrophysiologic effects of bepridil in the anesthetized closed-chest dog were studied with intracardiac electrodes using the extrastimulus technique to measure the refractory periods of atria, atrioventricular (AV) junction and ventricles. Intravenous administration of 5 mg/kg of bepridil caused a reduction in sinus node rate and prolonged the sinus node recovery time. Refractory periods in the atrium, especially the effective refractory period, increased.

Almitrine bismesylate: pharmacological review and structure-activity relationships.

In the anaesthetized dog almitrine bismesylate (A) increases ventilation after i.v. injections of more than 100 ug X kg-1.

Studies on the bradycardia induced by bepridil.

Bepridil, a novel active compound for prophylactic treatment of anginal attacks, induced persistent bradycardia and a non-specific anti-tachycardial effect, the mechanisms of which were investigated in vitro and in vivo. In vitro perfusion of bepridil in the life-support medium for isolated sino-atrial tissue from rabbit heart, caused a reduction in action potential (AP) spike frequency (recorded by KCl microelectrodes) starting at doses of 5 X 10(-6) M. This effect was dose-dependent up to concentrations of 5 X 10(-5) M, whereupon blockade of sinus activity set in.

Bepridil-induced modifications of cardiac performance in the anesthetized dog: comparison with nitroglycerin and propranolol.

Bepridil, a new anti-anginal drug, increases coronary blood flow and reduces myocardial oxygen consumption. The comparative effects of bepridil (2.5 mg.

2-Benzodioxinylaminoethanols: a new class of beta-adrenergic blocking and antihypertensive agents.

Various 2-benzodioxinylaminoethanol derivatives were synthetized and investigated for beta-adrenergic blocking activity. Most compounds demonstrated a beta-blocking activity of a competitive type when evaluated in guinea pig atrial and tracheal preparations. Three compounds were more potent than practolol and propranolol.

[Bepridil, a functional antagonist of beta1-adrenergic stimulation. Dissociated effects on cardiostimulation and lipolysis. (author's transl)].

1. Methods - In order to verify that the antagonism of isoprenaline by bepridil was not exclusive to cardiac receptors, anesthetized dogs were subjected to a double isoprenaline stimulation (two 15 minute perfusions at a rate of 1 microgram . kg-1 .

[Compared efficacies of somes antispasmodic drugs on the digestive tract and the bladder of the anesthetized dog (author's transl)].

The antispasmodic activity of tiemonium, mebeverine, pitofenone + fenpiverinium association and N-butyl scopolammonium was compared in the anesthetized dog. Strain gauges were fixed on the gastric antro-fundic border, on the pylorus, on the descending duodenum and on the terminal colon. Pressure transducers were connected with water filled small balloons inserted into the gall bladder and the bladder.

Mechanisms of anti-bronchoconstrictive effects of eprozinol. II. In vivo studies on the guinea pig.

The possible interactions of the anti-asthmatic compound, eprozinol, with bronchoconstrictors and adrenergic agents were investigated in the anaesthetised guinea pig by means of the following techniques: (1) study of the inhibition of histamine- and serotonin-induced bronchospasm; (2) investigation of potentiation or antagonism between the anti-bronchoconstrictor effects of eprozinol and isoprenaline; (3) investigation of propranolol-induced blockade of the anti-bronchoconstrictor effects of eprozinol and several reference compounds. In the anaesthetised guinea pig, eprozinol (5 mge . kg-1), isoprenaline (2 micrograms .

Comparative antidysrhythmic profiles of bepridil, amiodarone and disopyramide in the guinea-pig and dog.

The antiarrhythmic effects of a novel antianginal agent, bepridil, were compared with four reference products. Bepridil increased the effective refractory period in isolated guinea-pig atria slightly more than hydroquinidine, and much more than disopyramide and lidocaine. Amiodarone was without effect.

Vitamin B12 and a lyophilised extract of lamb gastric mucosa in the treatment of two digestive pathological models in the rat and the dog. Clinical and macroscopical observations.

A comparative experimentation between treatment with large amounts of vitamin B12 alone and associations of intrinsic factor with different concentrations of vitamin B12 in the gastrectomised dog and rat subjected to digestive stress induced by phenylbutazone is reported. This study served to examine the possible therapeutic role of vitamin B12 passive diffusion occurring with large amounts of cyanocobalamine in the digestive tract, and to verify the utility and efficacy of the intrinsic factor contained in the marketed Gastropylore, the composition of which associates an original lyophilisate of suckling lamb gastric mucosa (LLGM) with vitamin B12. Treatments with either of the components alone exerted no protective effect against phenylbutazone-induced ulcerations whereas Gastropylore gave very significant protection (p less than 0.