The effects of chloral hydrate, paraldehyde, and ethanol on the metabolism of C14 serotonin in the albino rat

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Serotonin is a biogenic amine which has been implicated by recent research as having an essential role in the proper functioning of the central nervous system. An ethanol induced alteration of serotonin metabolism has been shown to occur in man. Currently, the pharmacological and biochemical mechanisms of action for ethanol, as well as chloral hydrate and paraldehyde, are unresolved. Because of the clinical, structural, and biochemical similarities of ethanol, chloral hydrate, and paraldehyde, these agents were selected for testing in the rat. In this investigation, the effects of these drugs on the metabolism of intraperitoneally, intravenously, and intraventricularly administered C14-serotonin were studied. Albino rats were injected with tracer amounts of radioactive serotonin after treatment with one of the hypnotic agents. Urine was collected and assayed for C14-5-hydroxytryptamine, C14-5-hydroxyindoleacetic acid, and C14-5-hydroxytryptophol. Data were expressed as per cent of the radioactivity excreted in 24 hours. Various routes of administration were employed for the injection of C14-5-hydroxytryptamine. A decrease in total radioactivity excreted in 24 hours was observed for the rats receiving the C14-5-hydroxytryptamine intravenously. Chloral hydrate, like ethanol, altered the intermediate 14 metabolism of C14-5-hydroxytryptamine. An apparent inhibition of aldehyde dehydrogenase shifted the metabolism of C14-5-hydroxyindoleacetaldehyde from the oxidative route to a reductive route. This resulted in an increased excretion of C14-5-hydroxytryptophol and a reduction of urinary C14-5-hydroxyindoleacetic acid. Neither ethanol nor chloral hydrate had a detectable effect on the oxidation of C14-5-hydroxytryptamine by monoamine oxidase. Paraldehyde altered the metabolism of C14-5-hydroxytryptamine in more than one half of the animals studied. This drug caused an apparent inhibition of monoamine oxidase as well as an inhibition of aldehyde dehydrogenase in one third of the test animals. Other investigators have reported that younger rats tolerated paraldehyde better than older rats of the same colony. The relationship of the median lethal dose of paraldehyde for the rat as a function of the age of the animal warrants further investigation. This could explain the variation in the effect of paraldehyde on C14-5-hydroxytryptamine metabolism. These investigations demonstrated that ethanol, chloral hydrate, and paraldehyde modify the intermediate metabolism of C14-serotonin by an apparent common biochemical mechanism.