The relaxant effect of diazepam on rat tracheal strips.

The effect of diazepam was studied on the rat isolated trachea precontracted with acetylcholine 10-3M. Diazepam induced a dose dependent relaxant effect EC50 values 2.02 +/- 0.28.10(-4)M in controls (n = 38). The effect of diazepam was not modified by flumazenil (10-(6) to 10-(4) M) or RP 52028 (10-(6) to 10-(4)M) which are antagonists of central and peripheral benzodiazepines receptors respectively. No antagonism was observed between diazepam and nucleotides or endogenous ligands (adenosine 10(-6) to 10(-4)M, UTP 10(-6) to 10(-4)M, hématoporphyrin 10(-5) and 10(-4)M or nicotinamide 10(-5) and 10(-4)M). These results excluded an endogenous ligand-mediated interaction between nucleotides and diazepam. Propranolol (10(-7)M) did not modify the diazepam-induced relaxation, which excluded an involvement of beta receptors in diazepam relaxation. Theophylline (10(-7) and 10(-6)M), IBMX (10(-5) and 10(-4)M) rolipram (10(-5) and 10(-4)M) and siguazodan (10(-6) to 10(-4)M) displayed to the left the concentration-response curves to diazepam. The adenylcyclase activator forskolin (10(-7) to 10(-5)M, the beta adrenor stimulant isoprenaline (3.10(-5)M) and the direct acting G stimulant NaF (10(-3)M) also produced a leftward shift in the diazepam concentration-response curve. The relaxant concentration-effect curves to isoprenaline and to sodium nitroprusside were shifted to the left in a concentration-related manner by diazepam. Diazepam was more potent on the isoprenaline than on nitroprusside-induced relaxation. These results suggest that the diazepam-induced relaxation in the rat isolated trachea is mediated by an inhibition of cyclic nucleotide phosphodiesterases.

[The effect of certain active principles and excipients on the biodisposition of rectally administered acetylsalicylic acid in the rabbit]. / Influence de certains principes actifs et excipients sur la biodisponibilité de l'acide acétylsalicylique administré par voie rectale chez le lapin.

In this work, we have studied in the rabbit, bioavailability of acetylsalicylic acid contained respectively in three forms of suppositories which are made as follows: for the first by only acetylsalicyclic acid (0.1 g); for the second by the association: acetylsalicylic acid (0.1 g) and phenobarbital (0.01 g); and for the third by acetylsalicylic acid (0.01 g), ascorbic acid (0.02 g) and thiamine chloride (0.002 g). It has been shown that ascorbic acid and thiamine chloride do not change the bioavailability of acetylsalicylic acid, while phenobarbital decreases it. In this work we have also compared two pharmaceutical forms of suppositories containing acetylsalicylic acid, ascorbic acid and thiamine chloride. In one of the two forms, acetylsalicylic acid is buffered by glycocolle. The study which consisted in giving the two forms to the rabbit rectally was concerned with the effect of glycocolle on the bioavailability of acetylsalicylic acid. It was shown that making glycocolle a buffer to acetylsalicylic acid resulted in an improved absorption as well as a delayed elimination of acetylsalicyclic acid. In this study too, we have evaluated the bioavailability of acetylsalicylic acid which is released from two types of suppositories containing respectively base witepsol W31 and base cocoa butter. In order to study this bioavailability whole suppositories were administered by rectal route to the rabbits after 24 hours of fasting (balanced crossover design with 15 days of interval after each study). Statistical analysis does not reveal any significant difference between the two forms of suppositories.

[Chromopharmacokinetics of acetylsalicylic acid administered rectally the rabbit]. / Chronopharmacocinétique de l'acide acétylsalicylique administré par voie rectale chez le lapin.

Five white rabbits are given by rectal route a single dose of 100 mg of Aspirin at regular hours: 7 a.m.; 10 a.m. and 2 p.m. the 7 a.m. administration results in lowest CMAX and AUC and the slowest elimination, whereas 10 a.m. and 2 p.m. administration results in the highest CMAX and AUC and shortest elimination time.

[Bioavailability of acetylsalicylic acid administered orally or rectally in the rabbit]. / Biodisponibilité de l'acide acétylsalicylique administré par voie orale et rectale chez le lapin.

The aim of this study is to compare the bioavailability of acetylsalicylic acid administered rectally in suppositories form and orally in tablets form to the rabbit. Acetylsalicylic acid was given to 8 males rabbits rectally and orally in a balanced crossover design with 15 days of interval between each study. In blood samples, acetylsalicylic acid is determined by Trinder's method. It has been established that the rectal route has a faster absorption than the oral route however it displayed a more intense first pass effect than that of the oral route.

Effects of nifedipine, propranolol, adenosine and caffeine on benzodiazepines induced hyperglycaemia.

This study shows that diazepam (20 mg/Kg) and clonazepam (2 mg/Kg) administered intraperitoneally to 36 hour-fasted rabbits induce a significant (p < 0.05) hyperglycaemia 30 min. after administration. It also shows that the hyperglycaemic action of these benzodiazepines is significantly potentiated by nifedipine (10 mg/Kg) and inhibited by adenosine (1 mg/Kg), caffeine (40 mg/Kg) and propranolol (20 mg/Kg). The most pronounced inhibitory effect was that exerted by propranolol (p < 0.05). It is suggested that diazepam and clonazepam induced hyperglycaemia may be due to the release of hyperglycaemic hormones including adrenaline responsible for an increase of 3' 5' cAMP since the action of these benzodiazepines is inhibited by propranolol.

[Valeriana officinalis and Crataegus oxyacantha: toxicity from repeated administration and pharmacologic investigations]. / Valeriana officinalis et Crataegus oxyacantha: toxicité par administrations réitérées et investigations pharmacologiques.

The aim of this work is to study the toxicity of Valeriana officinalis and Crataegus oxyacantha after reiterated administrations. The study has been carried on the rat which received 300 and 600 mg/kg/24 h of the drugs for 30 days. During the period of the treatment, animals weight and blood pressure have been measured. On the end of the treatment the animals have been sacrificed. The principal organs have been weighed and in blood samples collected hematological and biochemical parameters have been determined. This work is concerned by pharmacological properties which are related to the two plants. The influence of the drugs on the behaviour, the pain, the intestinal peristalsis and strychnine convulsions are reported.

[Toxic effects induced by the repeat administration of Allium sativum L]. / Effets toxiques engendrés par une administration réitérée d'Allium sativum L.

Female and male rats were given 300 and 600 mg/kg/24 h of a Garlic bulb aqueous extract for 21 days. The results showed that garlic extract causes toxic effects affecting weight growth, biologic parameters and histologic structures.

[Hypotension, hypoglycemia and hypouricemia recorded after repeated administration of aqueous leaf extract of Olea europaea L]. / Hypotension, hypoglycémie et hypouricémie enregistrées à la suite d'une administration réitérée d'un extrait aqueux de feuilles d'Olea europaea L.

This study is concerned by the determination of the toxicity of an Olea europaea L.aqueous leaf extract after repeated administrations. Female and male rats were given 37.5, 75, 150, 300, 600 and 1200 mg/Kg/24h of the extract for 60 days. The results show that the drug studied induces an increase of weight growth, an hypotension, an hypoglycaemia and an hypouricaemia in treated animals.