| abstract |
The present invention relates to a method of inhibiting N-methyl-D-aspartate (NMDA) glutamate receptor-mediated ion channel activity (NMDA receptor activity), comprising contacting a neuronal cell (e.g., hippocampal neuron, spinal cord cell) with an effective amount (e.g., 1 to 500 mu M) of a derivative of pregnenolone sulfate. Derivatives of pregnenolone sulfate that inhibit NMDA receptor activity include pregnenolone sulfate in which the A ring includes at least one double bond or is fully unsaturated, the double bond at the C5-C6 position is reduced, the moiety at the C3, C10, C11 or C13 position is modified, alone or in combination. It further relates to pregnenolone sulfate derivatives which have modifications at other positions (e.g., C5, C7, C10, C16, C17, C18, C19, C20, C21), alone or in combination, and are inhibitors of NMDA recepteor activity. The pregnenolone sulfate derivatives differ from pregnenolone sulfate at least one position. The present invention also relates to a method of modulating or altering (e.g., potentiating; inhibiting) excitatory glutamate-mediated synaptic activity comprising contacting neurons with pregnenolone sulfate and derivatives of pregnenolone sulfate. |