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

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.A preliminary report of the present study was presented at the Scandinavian Pharmacological Society, June 1972, Uppsala, Sweden and the VIII C.I.N.P. Congress, August 1972, Copenhagen, Denmark.