Effects of some benzodiazepine derivatives on Triton WR-1339-Induced hyperlipidaemia in rats.

Oral administration of the benzodiazepines (diazepam, lorazepam, chlordiazepoxide, bipotassium chlorazepate) in Triton WR-1339-induced (200 mg/kg, blood collection 18 h later) hyperlipidaemia in rats elicited marked decrease of serum total lipids, total cholesterol and triglyceride levels, and alterations in free fatty acid and free glycerol content. The optimal doses for diazepam, lorazepam, chlordiazepoxide and bipotassium chlorazepate were estimated to be 5 mg/kg. Other benzodiazepines, namely oxazepam, medazepam and nitrazepam, elicited only minor changes in serum lipids levels, while with grandaxin no change was observed. The optimal doses of diazepam and lorazepam brought about the same changes in serum lipid content as did clofibrate (90 mg/kg, p. o.). If diazepam, lorazepam, chlordiazepoxide and bipotassium chlorazepate were administered in doses of 5 mg/kg in Triton WR-1339-treated rats (blood collection taken 3 h later), a significant decrease of total lipids and triglyceride levels was observed. The free glycerol level only altered after the administration of chlordiazepoxide, which brought about a significant reduction.

Experimental observations on the effect of amphepramone on the behavior, locomotion, pentretrazol seizures and electroencephalogram.

Amphepramone, an anorectic agent, has been found to possess stimulant properties on the C.N.S. in animals, producing hypermotility and stereotyped movements which can be antagonized with neuroleptics. The stimulant activity of amphepramone observed in animals can be correlated with the amphetamine like psychosis observed in humans.

Experimental anti-ulcer activity of Veronica officinalis L. extracts.

In indomethacin-induced ulcers in albino rats, the anti-ulcerogenic effects of some extracts prepared from Veronica officinalis L. were investigated. The extracts had a significant anti-ulcerogenic activity. In ulcer healing experiments performed in rats by administering reserpine, the extracts were found to enhance the regeneration of the gastric mucosa. These results seem to confirm the popular observations according to which the decoction from Veronica officinalis L. possessed useful properties in the treatment of gastric ulcers.

Effects of flumazenil (Ro15-1788) on blood glucose and serum lipids in normoglycemic and normolipidemic rats.

The intraperitoneal administration of flumazenil, an imidazoldiazepine with selective antagonistic properties on the central benzodiazepine receptors, induced in normoglycemic-normolipidemic rats a significant increase in blood glucose levels and significant decreases in the serum lipids.

Effects of 4'-chlordiazepam on glycemia and serum lipids in hyperlipidemic rats: interactions with PK 11195 and flumazenil.

In rats rendered hyperlipidemic by the interperitoneal injection of Triton WR-1339, the administration of 4'-chlorodiazepam, a selective agonist of the peripheral type of benzodiazepine (BZO) receptors evoked significant reductions of serum lipids. PK 11195, a specific antagonist of these receptors, partially inhibited these effects. Flumazenil, a selective antagonist of the central BZD receptors, enhanced the lipid lowering activity of 4'-chlorodiazepam.

Effects of some benzodiazepines on glycemia in albino rats.

The acute administration of some benzodiazepines in normoglycemic rats induced only minor changes of the blood glucose levels. In Triton WR-1339 administered rats, the benzodiazepines brought about minor modifications of this parameter. However, in diabetic rats (streptozotocin-induced diabetes), diazepam administered subacutely elicited very significant diminutions of glycemia. This was due, at least partly, to an increase of the glucose uptake by the skeletal muscle.

Cardiovascular effects of amphepramone.

The i.v. administration of amphepramone in dogs induced a dose-related depressor reaction. This effect was due to a peripheral myotropic vasodilatation. When the drug was administered intracerebroventricularly it elicited a marked pressor response, due, to the release of catecholamines with its subsequent action on alpha-adrenergic receptors. Small doses of amphepramone administered in dogs, rats and rabbits, induced a sinus tachycardia. Larger doses brought about a sinus bradycardia, bradyarrhythmias, extrasystoles, ventricular bradycardia and ventricular fibrillation or asystolia. The respiratory movements as well as the EEG tracings were depressed by larger doses of amphepramone.

Some central nervous actions of centrophenoxine (Meclofenoxat) in animals.

In experiments with rats and mice it was been found that centrophenoxine in acute experiments in large doses has inhibitory effects on the central nervous system. Centrophenoxine has no analgesic action. When administered subchronically, centrophenoxine aggravates both the pentetrazol and the maximal electroshock seizures.

Analysis of the mechanism of the protective activity of some sympathomimetic amines in experimental ulcers.

Apomorphine administered in reserpine-induced as well as in restraint ulcers in rats, failed to afford protection. Pimozide, moperone, trifluperidol and chlorpromazine fail to influence the development of the experimental ulcers. Pimozide and moperone although antagonizing the behavioral changes of amphetamine, maintained its antiulcer activity. Amitryptiline, cocaine and morphine had a protective activity. L-Dopa afforded a significant protection which was abolished if this compound was administered together with FLA-63, a specific dopamine-beta-hydroxilase inhibitor. These results were explained by admitting that not dopamine, but noradrenaline was responsible for the antiulcer activity. alpha-Methyl-dopa produced a significant protection in both experimental models.

Influence of some sympathomimetic amines on the experimental gastric ulcers in rats.

In reserpine-induced ulcers in rats, the centrally acting sympathomimetic ámines (amphetamine, mephentermine and ephedrine) produced a significant protection. Only amphetamine had a beneficial effect in restraint ulcers. Tyramine, a preponderant peripherally acting sympathominetic amine, was inefficient in both experimental models. It is suggested that the protective activity is due to the influence of these amines on the adrenergic structures, mainly at central level.

Effects of alpha-methylnoradrenaline and alpha-methyldopamine in reserpine-induced ulcers in rats.

alpha-Methyldopamine and alpha-methylnoradrenaline administered intraperitoneally afforded significant protection in reserpine-induced ulcers in rats. The optimal doses were 2 and 4 mg/kg. Lower and higher doses were less effective. alpha-Methyldopamine and alpha-methyl-noradrenaline probably act by reestablishing the normal adrenergic tone which is diminished in reserpine-induced ulcers.

Effects of peripheral type benzodiazepine antagonist PK 11195 on the lipid-lowering activity of diazepam in albino rats.

The i.p. administration of PK 11195, a peripheral type benzodiazepine receptor antagonist in a dose of 1 mg/kg/day antagonized the action of u.p. injection of diazepam (5 mg/kg/day, 5 days) on serum triglycerides. It seems that the effects of diazepam on serum lipids were due to the stimulation of the peripheral type benzodiazepine receptors.

Acute effects of zopiclone on blood glucose level and serum lipids in hyperlipidemic rats. Interactions with PK 11195 and flumazenil.

UNLABELLED: Intraperitoneal administration of 5 mg/kg zopiclone a cyclopyrolone acting on the central benzodiazepine receptors was found to produce significant reduction of total lipids, total cholesterol and triglyceride in rats randered hyperlipidemic by intraperitoneal injection of Triton W-1339. Blood glucose level was also reduced. Flumazenil (10 mg/kg) potentiated the hypoglicemic effect of zopiclone but had no additional effect on serum lipids. PK 11195 (25 mg/kg) antagonized the hypolipidemic effects of zopiclone. IN CONCLUSION: 1. The central benzodiazepine receptors are not involved in the hypolipidemic activity of zopiclone. 2. The peripheral type benzodiazepine receptors are partly responsible, for the hypolipidemic activity of this cyclopirrolone. 3. The changes of blood glucose level induced by these drugs does not seem to be related to benzodiazepine receptors.