Abstract
Effects of pentamidine, a therapeutic drug for Pneumocystis carinii pneumonia (PCP) in acquired immunodeficiency syndrome (AIDS), on specific bindings of [3H] (+)-5-methyl-10, 11-dihydro-5H-dibenzo [a, d] cyclohepten-5, 11-imine maleate (MK-801) and [3H] nitrendipine were investigated in crude synaptic membranes (CSM) of rat brain. Pentamidine inhibited [3H] MK-801 binding but did not change [3H] nitrendipine binding, althouth neither binding was inhibited by 3'-azido-2', 3'-dideoxycytidine (inhibitors for reverse transcriptase of HIV-1), or FK-506 or cyclosporin A (immunosuppressants). In Triton X-100-treated CSM (post-synaptic density-rich fractions), the inhibitory effect of pentamidine on [3H] MK-801 binding was partially prevented by addition of spermine and NMDA plus glycine (Gly). Electrophysiological experiments showed that pentamidine also inhibited Ca2+-current evoked by NMDA plus Gly in Xenopus oocytes injected with rat brain mRNA. These results suggest that pentamidine is a potent inhibitor for NMDA receptor/channels.
