Occurrence of a new class of tetrahydroisoquinoline alkaloids in L-dopa-treated parkinsonian patients

Abstract

THE chemotherapeutic administration of massive doses of L-3,4-dihydroxyphenylalanine (L-dopa) with or without peripheral decarboxylase inhibitors to parkinsonian patients can lead to aberrant metabolism which may influence the efficacy of the regime. It is generally agreed that the transformations can include spontaneous chemical reactions facilitated by the inherent reactivity of the catechol nucleus. For example, Sandler et al.¹ reported the excretion of tetrahydroisoquinoline alkaloids (TIQs), tetrahydropapaveroline (norlaudanosoline) and salsolinol by parkinsonian patients who had consumed large doses of L-dopa and ethanol. The same two TIQs have been detected in brain and urine of mammals administered alcohol and a second compound—for example, L-dopa or pyrogallol; and it has been proposed that these Pictet–Spengler condensation products (of dopamine and dopaldehyde or acetaldehyde, respectively) may be responsible for addiction in alcoholism^2–5. We report here the occurrence of a new class of TIQs, norlaudan-osolinecarboxylic acids (NLCAs), in the urine of parkinsonian patients on L-dopa with or without carbidopa. Comparative studies with rats on a similar regimen reveal the presence of NLCAs in brain as well as in urine.