The binding of strychnine and strychnine analogs to synaptic membranes of rat brainstem and spinal cord.

Crude synaptic membranes were isolated from rat pons, medulla and spinal cord by differential centrifugation. The specific binding of [3H]strychnine, obtained by subtracting from the bound radioactivity the amount not displaced by 50 micronm unlabeled strychnine, was saturable with a KD value of 12 nM. The dissociation constants (KD values) for the binding of several strychnine analogs to the strychnine site in vitro were determined and found to be highly correlated with the convulsant and lethal effects in the mouse. However, neither the biological activities in the mouse nor the binding activity in vitro correlated with the n-octanol-water distribution coefficients. The results are in accord with the concept that the [3H]strychnine binding site detected in vitro is the site of pharmacological activity in vivo.