Composition for modulating the glutamatergic system, useful e.g. in treating central nervous system disease, contains an arylcyclohexyl amine with specific affinity for non-N-methyl-D-aspartate sites

摘要

Composition (A) for modulating the glutamatergic system comprises at least one arylcyclohexyl amine (I) that has selective affinity for complementary molecular targets (II) of low affinity, i.e. 'non-NMDA' (N-methyl-D-aspartate) sites. ACTIVITY : Nootropic; Neuroprotective; Antiparkinsonian; Neuroleptic; Antiaddictive; Antialcohol. Animals were given a single intraperitoneal injection of 5 mg/kg dizocilpine (X; antagonist of NMDA receptors, known to provide excessive blockade of excitatory neurotransmitters, thus inducing hypofunctioning of the glutamatergic system). Some animals were also treated with an equal dose of cis(pip/me) 1-(1-(2-thienyl)-2-methylcyclohexyl)piperidine (Ia). Four days later, histological examination (staining with toluidine blue) indicated that the group given (X) only had cellular lesions in both the posterior cingular cortex and in the retrosplenial cortex, while those also given (Ia), although some neurons were necrotic, had better neuronal survival. The (Ia)-treated animals also showed increased expression of gliofibrillar acidic protein in astrocytes. MECHANISM OF ACTION : Glutamatergic System Modulator.