Dopamine-derived Alkaloid Research Articles

Alcohol induces formation of morphine precursors in the striatum of rats.

Dopamine-derived alkaloids, the tetrahydroisoquinolines (TIQs), are suspected to play a role in the pathogenesis of alcoholism. The present study describes the alcohol induced formation of the S-enantiomer of Tetrahydropapaveroline and Norcoclaurine in the rat brain. These compounds are of special interest since both were found as being intermediates in the biosynthesis of morphine in the opium poppy. The concentration of both TIQs were determined in different brain regions of Wistar rats after 6 and 18 months alcohol consumption ad libitum. Gas chromatography/mass spectrometry was used for the detection and quantification of the enantiomers. Tetrahydropapaveroline and norcoclaurine were detected only in the striatum of those rats which had consumed alcohol for 18 month, neither in other brain regions nor in any brain regions of the controls or the short term (6 month) alcohol treated rats. These findings and the fact that those tetrahydroisoquinolines were only detected in the striatum of the alcohol fed rats and were present only as the S-enantiomers suggest that an alcohol induced biosynthetic pathway exists in the mammalian brain.

Enzymatic oxidation of the dopaminergic neurotoxin, 1 ( R), 2( N)-Dimethyl-6,7-Dihydroxy- l,2,3,4-Tetrahydroisoquinoline, into 1,2( N)-Dimethyl-6,7-Dihydroxyisoquinolinium ion

The dopamine-derived alkaloid, 1( R),2( N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [N-methyl( R)salsolinol] was found to be oxidized enzymatically into the more cytotoxic species, 1,2( N)-dimethyl-6,7-dihydroxyisoquinolinium ion, using enzyme sample prepared from human brain cortex. The values of the Michaelis constant and of the maximum velocity were 912 μM and 1368 pmol/min/mg protein, respectively. The enzyme was not inhibited by inhibitors of monoamine oxidase, but was sensitive to semicarbazide. The oxidation is discussed in relation to the dopaminergic neurotoxicity of N-methyl-( R)salsolinol.

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

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.

In vivo studies of catechol-o-methyl transferase activity following intoxication with ethanol, L-dopa and dopamine-derived alkaloids

Only 20% inhibition in rat brain catechol-O-methyl transferase (COMT) activity was observed after chronic treatment with a 20% ethanol-water solution for 180 days. When L-dopa at 60 mg/Kg was administered to alcohol chronic rats, inhibition reached about 30%. Inhibition was 45% in experiments in which rats treated acutely with ethanol 5g/Kg in a unit dose were administered with L-dopa 60 mg/Kg. As regard tetrahydropapaveroline (THP) and salsolinol, 8 and 60 mg/Kg cause a slight but significant inhibitory effect for up two hours following treatment.