The effect of amitriptyline, desipramine and imipramine on the vivo brain synthesis of 3H-noradrenaline from 3H-L-dopa in the rat.
3H-L-Dopa was given to rats after a peripheral decarboxylase inhibitor Ro 4-4602 (50 mg/kg) and the effect of 30 min pretreatment with antiptyline (10 mg/kg), desipramine (10 mg/kg) and imipramine (10 mg/kg) on the brain formation of 3H-dopamine, 3H-noradrenaline and their major metabolites was investigated. Desipramine produced a decrease in the level of labelled noradrenaline and its major metabolites free and conjugated 3-methoxy-4-hydroxyphenyleneglycol and 3,4-dihydroxyphenyleneglycol. Imipramine decreased labelled noradrenaline and 3-methoxy-4-hydroxyphenyleneglycol, whereas amitriptyline produced no significant effect on noradrenaline metabolism. The thymoleptic drugs produced no significant effect on endogenous brain noradrenaline and dopamine. These findings provide a strong indication that desipramine and imipramine inhibit the 3H-noradrenaline biosynthesis from 3H-L-Dopamthe effect seems closely related to the well-known membrane inhibitory effect of these drugs, since desipramine produced a more marked effect than imipramine and amitriptyline showed no effect. No conclusive evidence for the precise mechanism of action was obtained but it is possible that the decreased 3H-noradrenaline synthesis is related to interference of desipramine and imipramine with the precursor (s) 3H-L-Dopa or 3H-dopamine at sites of 3H-noradrenaline biosynthesis.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000096:biosynthesis; D015098:3-Methoxy-4-hydroxyphenylethanol / Q000096:biosynthesis; D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001545:Benserazide / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000096:biosynthesis; D007099:Imipramine / Q000494:pharmacology; D007980:Levodopa / Q000378:metabolism*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000096:biosynthesis; D009638:Norepinephrine / Q000096:biosynthesis*; D009647:Normetanephrine / Q000096:biosynthesis; D051381:Rats; D014363:Tryptamines / Q000096:biosynthesis
D000929:Antidepressive Agents, Tricyclic; D014363:Tryptamines; D009647:Normetanephrine; D015102:3,4-Dihydroxyphenylacetic Acid; D000639:Amitriptyline; D015098:3-Methoxy-4-hydroxyphenylethanol; D007980:Levodopa; D008734:Methoxyhydroxyphenylglycol; D001545:Benserazide; D007099:Imipramine; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine