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J Simiand

Publications and source records attributed to J Simiand.

24 records · Page 2Linked to original sources
PubMed1983

The effects of analogues of valproic acid on seizures induced by pentylenetetrazol and GABA content in brain of mice.

The effect of valproic acid and 10 close analogues (7 branched and 3 non-branched) were studied on the content of gamma-aminobutyric acid (GABA) in brain and on seizures induced by pentylenetetrazol (PTZ) in mice. All 8 branched fatty acids protected against seizures induced by pentylenetetrazol, but the 3 non-branched acids were inactive. A significant correlation was observed between side-chain length and anticonvulsant potency. However, sedative and toxic phenomena became apparent with longer chain lengths. The 3 non-branched fatty acids did not alter levels of GABA in brain, but there was a significant correlation between anticonvulsant activity and increased brain GABA levels, for the 8 branched fatty acids. Despite this correlation, one branched analogue, 2-ethylbutyric acid, possessed anticonvulsant activity but did not increase the content of GABA in brain.

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PubMedDate not supplied

Benzodiazepine impairs and beta-carboline enhances performance in learning and memory tasks.

Benzodiazepines are widely used anxiolytics and anticonvulsants, and their potent sedative properties are routinely used in presurgical anaesthesia. However, they are also known to induce a strong anterograde amnesia in patients. Specific benzodiazepine antagonists have recently been described, some of which have intrinsic pharmacological properties that are opposite to those of benzodiazepines. These have been called inverse agonists and they have been shown to be proconvulsant or convulsant whereas benzodiazepines are anticonvulsants. Inverse agonists are also anxiogenic rather than anxiolytic. Since benzodiazepines induce anterograde amnesia, we have investigated the possibility that inverse agonists might also have an opposite effect for this property and so enhance acquisition (learning) and (or) retention (memory). We report here that, in three different animal models, an inverse agonist of the beta-carboline group, methyl beta-carboline-3-carboxylate (beta-CCM), enhances animal performance in three different tasks used to investigate learning and memory.

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PubMedDate not supplied

Comparative study in mice of tetrazepam and other centrally active skeletal muscle relaxants.

Tetrazepam is a 1,4 benzodiazepine (BZD) clinically used in France and Germany as a muscle relaxant. The activity of tetrazepam was compared to that of diazepam, baclofen, mephenesin and chlormezanone in mice, in pharmacological models which are predictive of muscle relaxant and sedative properties. Tetrazepam was active in all the 6 tests of muscle relaxation (traction, chimney, inclined screen, grip force, horizontal grid and morphine-induced Straub tail). The overall muscle relaxant potency of tetrazepam was inferior to that of diazepam, but was clearly superior to that of chlormezanone and mephenesin. Baclofen was less active than tetrazepam in 3 tests (traction, horizontal grid, and grip strength), but more active in the other 3 tests. The administration of the benzodiazepine receptor antagonist Ro 15-1788 blocked the effects of tetrazepam and diazepam in 2 representative tests, morphine-induced Straub tail and the rotarod test, but did not modify the activities of the other centrally acting muscle relaxants in these same models. The selectivity ratio (ED50 rotarod or ED50 locomotor activity/ED50 in each muscle relaxant test) for tetrazepam was superior to that of diazepam and all the other muscle relaxant drugs examined. It is concluded that tetrazepam exerts its muscle relaxant activity by stimulating central BZD receptors, and presents the advantage of a wide dissociation between muscle relaxant and sedative potencies.

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