dizocilpine-maleate and 2-3-piperidinedicarboxylic-acid

Excitatory amino acids and their analogues (NMDA, kainate and AMPA) are implicated in the pathogenesis of ischemic brain injury. In order to fully understand their involvement in the pathogenesis of retinal ischemic injury, we studied the electrophysiological and histopathological effects of two excitatory amino acid antagonists, cis-PDA and MK 801, in an experimental retinal ischemia model.. The two antagonists were injected intravitreously 15 min before ischemia was induced by elevatory intraocular pressure caused by external compression. Electrophysiological and histopathological evaluation was made 48 h after 45 min transient ischemia.. The excitatory amino acid antagonists cis-PDA and MK 801 can partially protect against retinal ischemic injury; whereas the mean post-ischemic b-wave amplitude corresponded to 41% of the pre-ischemic value in the control group, it was 64% (P = 0.003) and 59% (P = 0.005) following administration of cis-PDA and MK 801 respectively. Histopathological study corroborated these data, showing significant differences for morphometric parameters (P = 0.011 and P = 0.007 respectively).. These preliminary results suggest the possibility of limiting excito-toxicity, one of the lesion-forming mechanisms in ischemic retinal injury.

Topics: Animals; Disease Models, Animal; Dizocilpine Maleate; Electroretinography; Excitatory Amino Acid Antagonists; Injections; Ischemia; Pipecolic Acids; Rats; Reperfusion Injury; Retina; Retinal Vessels; Vitreous Body

Injection of the N-methyl-D-aspartate receptor agonist quinolinate, or N-methyl-D-aspartate itself, into the rat brain produces neurodegeneration which can be prevented by N-methyl-D-aspartate receptor antagonists administered up to 5 h after excitotoxin injection. The present study was designed to investigate aspects of the mechanisms involved in this delayed form of neurodegeneration. Following its injection into the rat striatum, extracellular levels of [3H]quinolinate were monitored using a microdialysis probe located 1 mm from the site of injection. Peak concentrations were observed 10-20 min after injection and [3H]quinolinate levels decayed in a biexponential fashion, the initial component having an apparent t1/2 of 13.7 +/- 5.2 min (n = 3). Estimations of the extracellular concentrations of quinolinate after an injection of 200 nmol indicated a peak level of 13.7 +/- 6.0 mM (n = 3) at 10-20 min which declined to 1.2 +/- 0.13 mM (n = 3) by 2 h and substantial levels were present up to 5 h, the period over which N-methyl-D-aspartate receptor antagonists are effective in this model. Administration of dizocilpine at 1, 2, 3 or 5 h after injection of 100, 200 or 400 nmol quinolinate resulted in a similar temporal profile of neuroprotection, as assessed by measuring the activities of choline acetyltransferase and glutamate decarboxylase in striatal homogenates, which was independent of the degree of neurodegeneration produced by the different excitotoxin doses. Overall, these results suggest that the neuronal degeneration caused by quinolinate in vivo is critically dependent upon events occurring after the initial peak of excitoxin levels in the extracellular space.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenergic alpha-Antagonists; Animals; Anticonvulsants; Convulsants; Corpus Striatum; Dialysis; Diazepam; Dizocilpine Maleate; Glutamate Decarboxylase; Haloperidol; Ibotenic Acid; Injections; Male; Nerve Degeneration; Pipecolic Acids; Piperazines; Piperidines; Quinolinic Acid; Quinolinic Acids; Rats; Rats, Inbred Strains; Stereotaxic Techniques

The effects of several excitatory amino acid receptor antagonists on sensory-evoked electromyographic activity induced by catechol have been studied in urethane-anaesthetised rats. 2-Amino-5-phosphono-valearic acid (1.2 mumol/kg i.c.), cis-2,3-piperidine dicarboxylic acid (1.4 mumol/kg i.c.), gamma-D-glutamyl-glycine (2.0 mumol/kg i.c.), 2-amino-7-phosphono-heptanoic acid (230 mumol/kg i.v.) and MK-801 (5 mg/kg i.p.) all significantly decreased the frequency of occurrence of those components of the sensory evoked EMG dependent on supraspinal structures, but were without effect on the spinal component.

Topics: 2-Amino-5-phosphonovalerate; Amino Acids; Animals; Catechols; Dibenzocycloheptenes; Dipeptides; Dizocilpine Maleate; Electromyography; Female; Pipecolic Acids; Rats; Receptors, Amino Acid; Receptors, Cell Surface; Seizures; Valine