Neuroprotective activity of a new class of steroidal inhibitors of the N-methyl-D-aspartate receptor

摘要

Release of the excitatory neurotransmitter glutamate and the excessive stimulation of N-methyl-D- aspartate (NMDA)-type glutamate receptors is thought to be responsible for much of the neuronal death that occurs following focal hypoxia-ischemia in the central nervous sys- tem. Our laboratory has identified endogenous sulfated ste- roids that potentiate or inhibit NMDA-induced currents. Here we report that 3α-ol-5β-pregnan-20-one hemisuccinate (3α5βHS), a synthetic homologue of naturally occurring pregnanolone sulfate, inhibits NMDA-induced currents and cell death in primary cultures of rat hippocampal neurons.