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

✍ Scribed by I. Zimányi; E. Wang; A. Lajtha; M. E. A. Reith

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 748 KB
• Volume: 22
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.490220214

✦ Synopsis

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, 428,140,004, 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-a-benzoate binding in mouse brain synaptosomes.