Effect of cocaine and cocaine congeners on veratridine‐induced depolarization in mouse cerebrocortical synaptoneurosomes

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Abstract
Structure‐activity relationships were determined for cocaine congeners in counteracting the depolarization induced by the action of veratridine on voltage‐dependent sodium channels of synaptoneurosomes from mouse brain cortex, and their potency was compared to those determined previously on Na+ uptake and batrachotoxinin binding. Cocaine, norcocaine, (+)‐pseudococaine, (‐)‐pseudococaine, (+)‐neopseudococaine, benzoyltropine, benzoylpseudotropine, ecgonine methylester, atropine, WIN‐35,428, WIN‐35,140, WIN‐35,065‐3, WIN‐35,004, and procaine were tested for their potency in inhibiting depolarization as measured by the distribution of the lypophilic cation [3H]triphenylmethylphosphonium across the membrane. All of the tested compounds inhibited the veratridine‐induced depolarization in a competitive manner. The structure‐activity relationships were similar to those for inhibition of 22Na+ uptake in mouse brain homogenates, and the potency of these local anesthetics in inhibiting veratridine‐induced uptake of [3H]triphenylmethylphosphonium correlated well with their potency in inhibiting [3H]batrachotoxinin A 20‐α‐benzoate binding in mouse brain synaptosomes.