MACROLIDE ANTIBIOTICS PROTECT NEURONS IN CULTURE AGAINST THE N-METHYL-D-ASPARTATE (NMDA) RECEPTOR-MEDIATED TOXICITY OF GLUTAMATE

The immunosuppressive macrolide FK-506 has been shown to protect neuro ns in culture against glutamate excitotoxicity. This effect was attrib uted to the binding of immunosuppressants to calcineurin-inhibiting im munophilins. We now report that also the non-immunosuppressive macroli de antibiotics protect neurons in culture against NMDA- but not kainat e-mediated excitotoxicity. The effect was structure-dependent: larger macrolide rings were more active. Macrolides did not affect the 3-(2-c arboxypiperazin-4yl)-propyl-1-phosphonic acid (CPP) binding or the NMD A-mediated calcium influx.