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Protriptyline induced inhibition of the in vivo 3H-noradrenaline synthesis from 3H-l-Dopa in the rat brain

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Summary

3H-l-Dopa was given intraperitoneally, after a peripheral decarboxylase inhibitor Ro 4-4602 (50 mg/kg), to male Wistar rats and the effect of protriptyline pretreatment (10 mg/kg, 30 min) on the formation and metabolism of the brain 3H-catecholamines, dopamine and noradrenaline and all their metabolites was investigated.

Protriptyline produced a strong decrease of labelled noradrenaline and its metabolites normetanephrine, free and conjugated 3-methoxy-4-hydroxyphenyl-eneglycol and 3,4-dihydroxyphenyleneglycol 60 and 120 min after 3H-l-Dopa. 3H-noradrenaline was also decreased 30 and 45 min after 3H-l-Dopa. In rats and mice the pretreatment with protriptyline (10 mg/kg, 30 min) induced also a significant decrease in brain 3H-noradrenaline but not 3H-dopamine synthesized from 3H-l-tyrosine. Protriptyline (10 mg/kg) produced no effect on endogenous dopamine and noradrenaline in the rat or mouse brain.

The present findings strongly indicate that the acute treatment with protriptyline inhibits the 3H-noradrenaline formation from 3H-l-Dopa. This effect seems most likely to be related to an interaction of protriptyline with the precursor(s) 3H-l-Dopa or 3H-dopamine at sites of 3H-noradrenaline biosynthesis.

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Nielsen, M., Eplov, L. & Scheel-Krüger, J. Protriptyline induced inhibition of the in vivo 3H-noradrenaline synthesis from 3H-l-Dopa in the rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 285, 15–28 (1974). https://doi.org/10.1007/BF00499525

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