ABSTRACT
Dimebon in low concentrations potentiated activity of AMPA-receptors in rat cerebellar Purkinje neurons, while memantine produced only an insignificant potentiation in a small group of these cells. In cortical neurons of rat brain memantine efficiently blocked NMDA-induced currents in dimebon-insensitive neurons. By contrast, its effect was far weaker in neurons, where the blocking action of dimebon on NMDA-receptors was most pronounced. It was hypothesized that the differences in the effects of memantine and dimebon are determined by their interaction with different sites of NMDA-receptors.
Subject(s)
Excitatory Amino Acid Antagonists/pharmacology , Indoles/pharmacology , Memantine/pharmacology , Neurons/metabolism , Receptors, AMPA/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Animals , Benzothiadiazines/pharmacology , Cerebral Cortex/cytology , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Excitatory Amino Acid Agonists/pharmacology , Kainic Acid/pharmacology , N-Methylaspartate/pharmacology , Neurons/drug effects , Patch-Clamp Techniques , Purkinje Cells/cytology , Purkinje Cells/drug effects , Purkinje Cells/metabolism , Rats , Receptors, AMPA/drug effects , Receptors, N-Methyl-D-Aspartate/drug effectsABSTRACT
Possibility of ortho-, para-, meta-methylphenyl and methoxyphenyl-derivates of MPTP to produce parkinsonism was investigated. Only ortho-methylphenyl- and ortho-methoxyphenyl-derivates of MPTP cause a persistent loss in dopamine content in the brain and produced the clinical symptoms of parkinsonism. All substances produced Parkinsonian-like syndrome gives the symptoms of activation of nervous system during 0.5-1 h after injection and symptoms of depression in following 3 h of observations.
