Stoffwechseluntersuchungen Des Cerebralen Anfallsgeschehens

Abstract

Zusammenfassung— Die Aktivität der Glutamat‐Decarboxylase im Gehirn von Ratten während und vor experimentell ausgelösten cerebralen Anfällen wird der von Kontroll‐ratten gegenübergestellt. Es konnte eine Hemmung der Enzymaktivitat im tonischen Krampf nach i.c. Injektion von l‐Glutamat, Pyridoxal‐5‐phosphat, nach audiogener Reizung, nach intraperitonealer Injektion von Pentamethylentetrazol und im Elektrokrampf beobachtet werden. Im prakonvulsiven Stadium ist das Enzym nach i.c. Injektion von l‐Glutamat, l‐Aspartat und nach audiogener Reizung stark gehemmt. Lediglich nach i.c. Injektion von Pyridoxal‐5‐phosphat ist die Enzymaktivitat gegeniiber von Kontroll‐ratten unverändert. Insbesondere wird auf die unterschiedliche Wirkung auf l‐Glutamat und Pyridoxal‐5‐phosphat in vivo und in vitro auf die Glutamat‐Decarboxylase hingewiesen. Die Hemmung dieses Enzyms in vivo wird als eine der moglichen Ursachen für die Entstehung cerebraler Anfälle vermutet.

CHANGES IN GAMMA-AMINOBUTYRIC-ACID-SHUNT ENZYMES AND SUBSTRATES AFTER ADMINISTRATION OF CARBONYL REAGENTS AND VITAMIN B6IN VIVO: AN APPARENT DISCREPANCY IN ASSAY TECHNIQUES

“…This explanation of the biochemical findings fits all of the known facts and finds further support in the recent observations of others. 43 In order to reconcile it with physiological parameters, such as the rapid anticonvulsant effect of PAL in vitamin B6-deficient children and TSC-poisoned rats, one must assume also that the anticonvulsant effect under these conditions is primarily (at least in the beginning) an effect at membrane surfaces and not a specific effect upon the reactivation of the GAD apoenzyme. In this connection, it has been pointed out that the interaction of B6 vitamers with membrane surfaces is to be expected.44 e. Other Uncertainties and Implications.…”

p-Substituted N-acetyl-L-(S)- and D(R)-.alpha.-amino-N-phenylsuccinimides and -glutarimides. Substituent effects on stereoselective anticonvulsant activity

“…It is known that during various experimentally induced convulsions the enzymes which reduce the concentration of glutamic acid (glutamate decarboxylase and glutamine synthetase) are inhibited in the CNS, while those which increase the concentration of glutamic acid (glutaminase and glutamate dehydrogenase) form glutamic acid to an increased extent. 3 This results in a considerable increase in free glutamic acid in the brain. It has been proposed that glutamic acid, which exerts a strong excitatory effect upon the nerve cell, possibly constitutes the chemical stimulus which is largely responsible for the convulsive seizure.…”

“…In addition to glutamic acid, aaminobutyric acid, alanine, aspartic acid, and glutamine also show a rise in concentration during experimentally induced seizures. 3 For these reasons, it seemed likely that compounds 1-10, which contain a chiral center a to one of the imide C=0 groups, would satisfy the two requirements listed above. In this communication the toxicity, anticonvulsant activity against minimal and maximal seizures, and the protective index (PI) of the semirigid succinimides and more flexible glutarimides are compared with the results obtained for standard drugs in the same biological system.…”

“…Indanylamine itself was found to be endowed with analgetic properties 3. Molecular models show that the plane of the aromatic…”