Dopamine-derived alkaloids in alcoholism and in Parkinson's and Huntington's diseases

Abstract

Tetrahydroisoquinoline (TIQ) alkaloids and 1-carboxy TIQ derivatives have been found in human fluids and/or tissues. The possible biosynthetic pathways of salsolinol (Sal), taken as an example of TIQs, are discussed, and the possibility that biosynthesis occurs through a stereospecific enzymatic reaction is considered. In this respect, it is reported that the R enantiomer of Sal predominates in urines of healthy volunteers, whereas the S enantiomer predominates in port wine and possibly in other beverages and foods, suggesting that Sal present in humans could have, at least partially, and endogenous enzymatic origin. TIQs and other dopamine-derived alkaloids are weak MAO inhibitors, the R enantiomer of Sal and salsolidine being more potent than the S form. The changes in monoamine oxidase activity and the nigrostriatal concentrations of dopamine and homovanillic acid in Parkinson's and Huntington's diseases and in alcoholism are reviewed. In these pathological situations, changes in the levels of dopamine-derived alkaloid levels may occur. The possibility that the modifications found might cause or contribute to changes in mental and/or neurophysiological states in these pathological situations is considered.

Confirmation of the enantiomers of 1-methyl-1,2,3,4-tetrahydroisoquinoline in the mouse brain and foods applying gas chromatography/mass spectrometry with negative ion chemical ionization

“…3 5 ) to that of Sal found in port wine. 4 Our result suggests that in oioo formation of 1 MeTIQ proceeds via an enzymatically assisted reaction, but details of the biosynthetic route of lMeTIQ are at this time unclear. We found significantly decreased concentrations of lMeTIQ in the frontal lobe of parkinsonians compared to controls.'…”

Uptake of a neurotoxin-candidate, (R)-1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline into human dopaminergic neuroblastoma SH-SY5Y cells by dopamine transport system

“…The selective transport of (R)-I,2-DiMeDHTIQ by dopamine transporter, intracellular oxidation into more cyctotoxic ion, and the accumulation may be the most important mechanism underlying the neurotoxicity of 1,2-DiMeDHTIQ to dopaminergic neurons. (S)-I-MeDHTIQ occurs in some foods, such as port wine (Dostert et al, 1988), but it cannot pass through the blood-brain barrier (Origitano et al, 1981), indicating that 1-MeDHTIQ found in the brain should be the (R)-enantiomer synthesized in situ (Dostert et al, 1990). From their different origins, biological activity of the (R)-and (S)-enantiomer of 1-MeDHTIQ and their N-methylated derivatives has been suggested to differ each other.…”

“…1-MeDHTIQ is synthesized in the brain by condensation of dopamine with pyruvic acid, followed by decarboxylation and possibly enzymatic reduction, which yields the (R)-enantiomer under physiological conditions (Dostert et al, 1990;Strolin Benedetti et al, 1989). In the urine of healthy human controls, only (R)-I-MeDHTIQ was detected (Dostert et al, 1990), while the (S)-enantiomer is dominant in wine and other foods (Dostert et al, 1988). When the concentration of dopamine or acetalcehyde increases, as in the patients treated with L-DOPA or of alcoholism, both (R)-and (S)-I-MeDHTIQs are supposed to be synthesized by nonenzymatic Pictet-Spengler reaction of dopamine with acetaldehyde.…”

Biosynthesis of salsolinol, a tetrahydroisoquinoline alkaloid, in healthy subjects

“…1,2-Dehydrosalsolinol has been reported to be a potent inhibitor of catechol-O-methyltransferase (Cheng et al, 1987) Its increased formation after administration of Madopar might contribute to the beneficial effects of L-dopa therapy by inhibiting one of the catabolic pathways of DA. Thus, 1,2-dehydrosalsolinol should be considered as one of the dopamine-derived alkaloids which may play a role in pathological situations, such as alcoholism and Parkinson's disease (Sourkes, 1971;Dostert et al, 1988).…”