Abstract
H13/04, an audiogenic seizure-inducing catecholamide, has previously been demonstrated to decrease the accumulation of 5-hydroxytryptophan (5-HTP), while increasing the accumulation of dihydroxyphenylalanine (DOPA) after aromatic acid decarboxylase inhibition in vivo. The present study examined the effect of H13/04 on intracellular storage, release, and metabolism of serotonin (5-HT) and noradrenaline (NA) in vitro in order to differentiate between the primary effects of the drug and possible secondary effects due to neurotransmitter interaction. H13/04 had no effect on NA synthesis by brain minces from C57BL/6 mice, but did have a marked effect on [3H]5HT synthesis from [3H]tryptophan in mouse brain minces. H13/04 was subsequently shown to competitively inhibit tryptophan hydroxylase. The data presented in this study indicate that the primary action of H13/04 on biogenic amines is to decrease the synthesis rate of 5-HT by competitive inhibition of tryptophan hydroxylase. The lack of any effect on NA in vitro is consistent with the hypothesis that the primary biochemical action of the drug is on the 5-HT system and that the action on NA in vivo is an indirect effect possibly secondary to the inhibition of 5-HT synthesis.
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Stine, S., Kellogg, C. Inhibition of tryptophan hydroxylase: Neurochemical action of a catecholamide seizure-inducing agent. Neurochem Res 7, 87–98 (1982). https://doi.org/10.1007/BF00965072
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DOI: https://doi.org/10.1007/BF00965072