Glutamic Diethyl Ester Research Articles

The excitation of mammalian central neurones by amino acids.

1. The relative potencies of a number of analogues of L-glutamate as excitants of thalamic neurones in the rat have been compared. The most powerful compounds were kainate, ibotenate and (+/-)cis-1-amino-1,3-dicarboxycyclopentane. The D- and L-isomers of glutamate and aspartate were also compared. Whereas D-glutamate is approximately one-half as active as the L-form, D-aspartate is more potent than L-aspartate. 2. Computer analysis has indicated that ibotenate and cis-1-amino-1,3-dicarboxy-cyclopentane have relatively fixed and similar C alpha-N, Comega-N and C alpha-Comega interatomic distances which can also be achieved by glutamate in certain conformations of the molecule, but not by aspartate. 3. Parallel examination of the antagonists glutamate diethylester and D-alpha-aminoadipate has shown that the former preferentially reduces L-glutamate effects while the latter blocks the actions of other amino acid excitants more readily than those of L-glutamate. 4. The evidence is consistent with the hypothesis that at least two populations of neuronal receptors for the excitatory amino acids exist.

Glutamic acid and ethanol dependence

Glutamate diethyl ester, a specific glutamate antagonist, attenuated the seizures and decreases in behavioral activity that were observed in mice during withdrawal. Prior to withdrawal, ethanol-dependent animals were supersensitive to kainic acid, a potent glutamate agonist, but they were not supersensitive to the convulsant drug pentylenetetrazol. These findings suggest that supersensitivity to glutamate develops during ethanol dependence, and that this phenomenon contributes to the signs of ethanol withdrawal.

Effects of glutamate and glutamic acid diethyl ester on the lobster muscle fibre and the frog spinal cord

The effect of bath applications of glutamic acid diethyl ester (GDE) and glutamate on the lobster muscle fibre and the from spinal cord were examined. In the lobster muscle fibre GDE (2 X 10(-3) M) did not antagonize the depolarizing action of glutamate (10(-4) M). In the frog spinal cord a small reduction in the excitatory effects of glutamate (10(-4)-10(-3) M) after GDE pretreatment was found only if the latter was given in very high doses (over 2 X 10(-3) M) which stimulated the neuronal firing. These observations show that GDE is not a specific antagonist of glutamate in these tissues.

The antagonistic action of glutamic acid diethylester towards amino acid-induced and synaptic excitations of central neurones

Summary The previously reported reversible antagonism of glutamate-induced neuronal excitation by the diethylester of the acid amino has been confirmed, and its greater effectiveness against glutamate by contrast with other amino acid excitants established. Glutamate dimethylester usually increased amino acid excitations. Methionine sulphoximine also antagonized amino acid effects, but without any specificity of action. Glutamate diethylester also reduced the synaptic activation of cells in the spinal cord, cuneate nucleus and ventrobasal thalamus.

Induction of abnormal cell division in Euglena gracilis by glutamic diethyl ester.

SYNOPSIS. Glutamic diethyl ester inhibited the growth of Euglena gracilis and induced abnormal cell division. A variety of amino acid esters inhibited growth in both Euglena and Astasia, but only glutamic diethyl ester and, to a lesser extent, glutamic dimethyl ester, interfered with cell division, and only in Euglena. Glutamic acid potentiated the growth inhibitory effect of glutamic diethyl ester but antagonized the formation of aberrant division forms. The mitotic process appeared to proceed normally thru the stages of formation of the reservoir, gullet and flagellum, but cytokinesis stopped during the unwinding process which leads to the separation of the daughter cells, thus leading to the formation of doublets. Doublets could then continue their life cycles, forming triplets or quadruplets and, occasionally, octuplets.

Sanitary Authorities and Hospital Accommodation

Recent anatomic and physiologic experiments revealed that a major afferent to the nucleus locus coeruleus (LC) is the nucleus paragigantocellularis (PGi) in the rostral ventrolateral medulla (Aston- Jones et al., 1986). In the present studies, responses of LC neurons to electrical activation of PGi were characterized in anesthetized rats. Low-intensity stimulation of PGi synaptically activated 73% of LC neurons at short latencies (mean onset, 11.3 msec), while a smaller population (16%) of LC neurons exhibited purely inhibitory responses. The excitatory transmission from PGi to LC was pharmacologically analyzed, revealing it to be resistant to cholinergic receptor antagonism, but completely abolished by the excitatory amino acid (EAA) antagonists kynurenic acid and gamma-D-glutamylglycine. The specific N- methyl-D-aspartate antagonist 2--amino-7-phosphonoheptanoic acid (AP7) and the preferential quisqualate receptor antagonist glutamate diethyl ester (GDEE) did not block LC responses to PGi stimulation, leading us to the tentative conclusion that EAAs may operate primarily at a kainate-type receptor on LC neurons to effect excitation from PGi. In addition to their blockade of PGi-evoked activity, kynurenic acid and DGG exerted a similar, simultaneous blockade of the characteristic excitation of LC neurons evoked by electrical stimulation of the hindpaw. These and other results indicate that the proposed EAA pathway from PGi may serve as a final link in a variety of sensory inputs to LC.