The opioid peptide dynorphin directly blocks NMDA receptor channels in the rat.

1. The actions of dynorphin on N‐methyl‐D‐aspartate (NMDA) responses were examined in acutely dissociated trigeminal neurons in rat. Whole‐cell and single‐channel currents were recorded using the patch clamp technique. 2. Dynorphins reduced NMDA‐activated currents (INMDA). The IC50 was 0.25 microM for dynorphin (1‐32), 1.65 microM for dynorphin (1‐17) and 1.8 microM for dynorphin (1‐13). 3. The blocking action of dynorphin is voltage independent. 4. The inhibitory action of dynorphin cannot be blocked by high concentration of the non‐selective opioid receptor antagonist naloxone, nor by the specific kappa‐opioid receptor antagonist nor‐Binaltorphimine (nor‐BNI). 5. Single‐channel analyses indicate that dynorphin reduces the fraction of time the channel is open without altering the channel conductance. 6. We propose that dynorphin acts directly on NMDA receptors.