Neuroamine-derived alkaloids: Substrate-preferred inhibitors of rat brain monoamine oxidase in vitro

6,7-Dihydroxy-1,2,3,4-tetrahydroisoquinoline (norsalsolinol) and 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), and their N-methylated derivatives were found to inhibit type A and B monoamine oxidase isolated from human brain synaptosomal mitochondria. N-Methyl-norsalsolinol, (R) and (S) enantiomer of salsolinol, and N-methyl-salsolinols inhibited type A monoamine oxidase competitively to the substrate, kynuramine, and R enantiomers were more potent inhibitors than S enantiomers. The inhibition was reversible. Norsalsolinol induced positive cooperativity toward kynuramine. Both norsalsolinol and N-methyl-norsalsolinol inhibited type B oxidase non-competitively to the substrate, and their Ki values were much higher than those to type A. Types of inhibition of type A monoamine oxidase depended on the enzyme sources. Inhibition of monoamine oxidase by 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines is discussed in relation to their chemical structures.

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“…It coincides with the results of rat brain MAO-B, which was inhibited by SAL non-competitively (Meyerson et al, 1976).…”

Section: Discussionsupporting

confidence: 84%

Inhibition of type A and B monoamine oxidase by 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines and their N-methylated derivatives

Minami

Maruyama

Dostert

et al. 1993

J. Neural Transmission

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“…The effects of (4-)-Sal and of other (+)-TIQs on MAO activities have been evaluated using rat brain homogenates (Meyerson et al, 1976) or rat brain mitochondria (Giovine et al, 1976). Sal was found to be a relatively weak selective and competitive MAO-A inhibitor (Ki = 48 laM), whereas THP was about 5 times less potent (Ki = 2601.tM) (Giovine et at.,t976).…”

Section: Inhibition Of Monoamine Oxidase (Mao) By Da-derived Alkaloidsmentioning

confidence: 99%

“…Sal was found to be a relatively weak selective and competitive MAO-A inhibitor (Ki = 48 laM), whereas THP was about 5 times less potent (Ki = 2601.tM) (Giovine et at.,t976). In addition (4-)-2,3,10,11-tetrahydroxyberbine (THB), a THP-derived alkaloid, was shown to be a more potent and selective MAO-A inhibitor than (4-)-Sal [IC 50 = 40 taM and 250 gM (5-HT) for 2,3,10,11-THB and Sal, respectively], whereas (4-)-2,3,9,10-THB was as potent as Sal but less selective (Meyerson et al, 1976) (Fig. 6).…”

Section: Inhibition Of Monoamine Oxidase (Mao) By Da-derived Alkaloidsmentioning

confidence: 99%

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

Dostert¹,

Benedetti²,

Dordain

1988

J. Neural Transmission

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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.

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“…In fact, it is of interest to emphasize that some authors suggested that TIQs possess differing pharmacological properties (2,3,19,35,38,41), alter neuroamine uptake and release (2 ,8 , 17, 19, 27), and have inhibitory effects on MAO activity in vitro (5,8,9) and in vivo (7,15). In particular SALS seems to be a preferred inhibitor substrate of type A MAO, whereas THP a relatively nonspecific inhibitor of rat brain MAO (30). Thus, these alkaloids may be implicated in some of the pharmacological and behavioral actions related to alcohol abuse (6,9,11,12) or ¿-dopa therapy in Parkinson's disease (13,21).…”

Section: Discussionmentioning

confidence: 99%

MAO Activity in Rat Brain Stem and Cerebral Cortex following Acute and Chronic Treatment with <i>L</i>-Dopa and Ethanol + <i>L</i>-Dopa

Renis¹,

Giovine²,

Bertolino³

1977

Pharmacology

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This work reports the effects of acute and chronic administration of L-dopa and ethanol + L-dopa on MAO activity in rat brain stem and cerebral cortex using noradrenaline (NA), dopamine (DA), serotonin (5-HT) and tryptamine (Try) as substrates. The results obtained clearly demonstrate that acute and chronic treatment affects MAO activities in the two brain areas examined in opposite ways. Moreover, the two treatments show different effects both according to the substrate used, and, especially in the case of NA and Try, according to the brain area examined.

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Neuroamine-derived alkaloids: Substrate-preferred inhibitors of rat brain monoamine oxidase in vitro

Cited by 45 publications

References 61 publications

Inhibition of type A and B monoamine oxidase by 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines and their N-methylated derivatives

Inhibition of type A and B monoamine oxidase by 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines and their N-methylated derivatives

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

MAO Activity in Rat Brain Stem and Cerebral Cortex following Acute and Chronic Treatment with <i>L</i>-Dopa and Ethanol + <i>L</i>-Dopa

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