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Interactions of benztropine, atropine and ketamine with veratridine‐activated sodium channels: effects on membrane depolarization, K + ‐efflux and neutrotransmitter amino acid release
Author(s) -
Erecińska Maria,
Nelson David,
Silver Ian A.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11599.x
Subject(s) - veratridine , benztropine , chemistry , depolarization , pharmacology , atropine , niflumic acid , sodium , efflux , sodium channel , biophysics , biochemistry , endocrinology , biology , organic chemistry , dopamine
1 The effect of benztropine, atropine and ketamine on veratridine‐induced efflux of K + , membrane depolarization and release of amino acid neurotransmitters was investigated in the preparation of rat brain synaptosomes. 2 All three drugs inhibited in a concentration‐dependent manner the processes measured: the most effective compound was benztropine which exhibited an approximate K d of 2 μ m . The inhibition was not competitive in nature. 3 The veratridine titration curves in the presence of drugs were sigmoid with Hill coefficients of about 1.4. 4 At higher concentrations, benztropine, atropine and ketamine blocked uptake of amino acid neurotransmitters into synaptosomes. 5 It is postulated that benztropine, atropine and ketamine interfere with the veratridine‐activated influx of sodium into synaptosomes through voltage‐dependent channels by acting at the same site as local anaesthetics. Interactions at this site alter allosterically binding and action of veratridine. In addition, at higher concentrations the drugs interact with the carrier proteins for amino acid neurotransmitters and block their transport.