Effect of cocaine and cocaine congeners on veratridine-induced depolarization in mouse cerebrocortical synaptoneurosomes.
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-alpha-benzoate binding in mouse brain synaptosomes.
Zimányi
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Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, Wards Island, New York, NY 10035.
Wang
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Lajtha
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A
Reith
M E
ME
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D003042:Cocaine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007202:Indicators and Reagents; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009861:Onium Compounds / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology*; D014320:Triphenylmethyl Compounds / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology*; D014702:Veratrine / Q000031:analogs & derivatives*
D000779:Anesthetics, Local; D007202:Indicators and Reagents; D009861:Onium Compounds; D015222:Sodium Channels; D014320:Triphenylmethyl Compounds; C011561:triphenylmethylphosphonium; D014701:Veratridine; D014702:Veratrine; D003042:Cocaine