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The effects of alcohols and diols at the nicotinic acetylcholine receptor of the neuromuscular junction

The effects of alcohols and diols at the nicotinic acetylcholine receptor of the neuromuscular junction

Brain Research 295(1): 101-112

ISSN/ISBN: 0006-8993

PMID: 6608971

DOI: 10.1016/0006-8993(84)90820-5

A series of straight chain aliphatic alcohols from ethanol to octanol were tested at voltage-clamped frog endplates. In the presence of high concentrations of ethanol (greater than 1 M) the individual current responses to ionophoretic pulses of ethanol were reduced in amplitude and the dose-response curve for acetylcholine was shifted to the right. All the alcohols tested had this effect and their potency increased with the length of the carbon chain. The results were interpreted to indicate that as the molecular weight of the alcohol increased, its potency as a channel blocker also increased. The diol derivative of ethanol, which is ethylene glycol (ethanediol), was totally inactive up to 400 mM. However, 1,3-propanediol was a more potent blocker than propanol. After dose-response curves were carried out in high doses of ethanol and propanediol, the number of receptors was found to be permanently reduced. This effect could be due to irreversible denaturation of the receptor and therefore reversible denaturation could account for some of the reversible blocking effects caused by such drugs. An additional effect on the receptor was observed in that low concentrations of ethanol and propanol reduced the apparent dissociation constant for acetylcholine, thus increasing the amplitude of individual responses and shifting the dose-response curve to the left.

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Accession: 044624721

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