Effects of prolonged administration of certain antihypertensive agents.
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Biomedical subjects
Publications and source records attributed to D E Clarke.
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1 The effect of a wide range of ethanol concentrations (v/v) on indoleacetic acid (IAA) formation from the oxidative deamination of tryptamine was studied in vitro, in rat whole liver homogenate.2 IAA production was inhibited progressively by ethanol in concentrations between 0.01% to 0.2%, but the inhibition declined when the ethanol concentration was increased further to 6%.3 Ethanol-induced inhibition of IAA formation was only partially reversed by excess aldehyde dehydrogenase, whereas reductions in IAA formation were completely prevented by pyrazole or ethanol (6% and 10%) itself.4 Excess nicotinamide adenine dinucleotide failed to alter the inhibitory effect of ethanol and no evidence was obtained for inhibition of monoamine oxidase by ethanol or its metabolite, acetaldehyde.5 We conclude that ethanol indirectly inhibits IAA production as a result of oxidation of ethanol by alcohol dehydrogenase, during which the oxidative metabolism of tryptamine is shifted towards the reductive pathway, thus favouring the formation of tryptophol in place of IAA.
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1. Bretylium, BW392C60, bethanidine, nialamide and pheniprazine, but not guanethidine or ouabain, were all capable of restoring the cardiovascular response to tyramine in reserpine pretreated rats anaesthetized with sodium pentobarbitone.2. In parallel with their recorded in vitro activity as monoamine oxidase inhibitors, BW392C60 was found to be more potent at restoring the response to tyramine than bretylium or bethanidine.3. The restored responses to tyramine were completely blocked by desmethyl-imipramine or by a combination of phentolamine and propranolol.4. The effect of bretylium on the tyramine response was not influenced by bilateral adrenal demedullation, urethane anaesthesia, the dose or duration of the reserpine pretreatment and was not dependent upon the frequency of the tyramine injections.5. Bretylium, BW392C60 or bethanidine did not alter the pressor response to intravenous noradrenaline.6. Nialamide-induced restorations of the responses to tyramine were not further enhanced by the administration of bretylium, BW392C60 or bethanidine.7. In pithed reserpine-treated rats the ability of bretylium and BW392C60 to restore the response to tyramine was reduced.8. It is concluded that all the drugs which reversed the reserpine-induced subsensitivity to tyramine were acting as monoamine oxidase inhibitors, thus allowing the intra-neuronal accumulation of endogenously formed catecholamines. The presence of nerve impulses in the adrenergic fibres of reserpinized rats appears to be an important factor in mediating this effect.
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