Effect of L-Dopa Therapy on Urinary p-Tyramine Excretion and EEG Changes in Parkinson's Disease

Abstract

P-TYRAMINE is a normal constituent of human urine^1–8, excreted in free and conjugated forms^2,4,8. The level of excretion is quantitatively evaluated by separating the phenolicamine fraction (isolated by absorption onto a ‘Biorad AG50W-X2’ column¹) overnight in isopropylether: methylethyl ketone : acetic acid : water 9 : 1 : 5 : 5 (v/v) on a Whatman No. 2 paper strip followed by conversion to the 1-nitroso-2-naphthol fluorophore and photodensitometric evaluation⁹. This procedure has shown that approximately 60% of Parkinson patients excrete more unconjugated urinary p-tyramine than does a control group^4,8,10. Food precursors rich in p-tyramine were shown to increase the levels of conjugated p-tyramine and its principal acid metabolite p-hydroxyphenylacetic acid (both free and bound forms)^4,8,11. These three metabolites increased so as to account almost stoichometrically for the ingested amine⁴. Sterilization of the intestinal tract with neomycin and succinyl sulphathiazole in a patient with Parkinson's disease caused a considerable increase in both free and bound forms of both amine and acid⁴. These findings suggest that a proportion of conjugated p-tyramine and total p-hydroxyphenylacetic acid arise from exogenous sources whereas most of the free urinary p-tyramine is endogenous⁸. This observation is confirmed in the work of several others^5–7 although Perry et al.⁷ interpret their findings differently. A more convincing demonstration of the validity of our hypothesis followed from an assessment of the urinary free and bound p-tyramine and p-hydroxyphenylacetic acid excreted in urine after oral and intravenous administration of p-hydroxyphenyl(ethylamine-2-¹⁴C)-hydrochloride. In a control population only a tiny proportion of ingested p-tyramine, even when substantially supplemented with cold amine, is excreted in the urine in the free form (Table 1). After intravenous injection, however, a variable but significant amount of unconjugated amine is excreted.