Phencyclidine receptor ligands attenuate cortical neuronal injury after N-methyl-D-aspartate exposure or hypoxia

摘要: Phencyclidine (PCP) and related noncompetitive antagonists of N-methyl-D-aspartate (NMDA) receptor neuroexcitation were tested for their ability to attenuate either NMDA- or hypoxia-induced neuronal loss in dissociated cell cultures prepared from mouse neocortex. 10 microM PCP MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate] selectively blocked the neurotoxicity produced by application NMDA endogenous agonist quinolinate, without altering kainate quisqualate neurotoxicity. Blockade toxicity was concentration-dependent submicromolar micromolar range, with a potency order (MK-801 greater than SKF 10,047 pentazocine) consistent primary mediation at sites rather sigma sites. reduced high concentrations, mechanism antagonism. ligands also potently attenuated injury after exposure hypoxia. The effective concentrations drug blockade hypoxic quantitatively similar results obtained against exogenous NMDA. These observations provide further support hypothesis that excessive activation receptors may participate importantly pathogenesis brain injury.