The route and significance of endogenous synthesis of alkaloids in animals

Abstract

There is now substantial evidence that several TIQs and beta-carbolines are present in vivo and increase during certain pathological conditions. It still remains to be determined, however, precisely what roles they play in endogenous functions and whether or not they are critical for the expression of these pathological conditions. Accumulating biochemical information continues to support the notion that these compounds can act as false transmitters. The exciting new findings, which will certainly receive a great deal more attention, concern the interaction of some of the beta-carbolines with the benzodiazepine receptor. Determining if a beta-carboline is an endogenous receptor ligand will attract further research interest on the theoretical and specifically clinically-directed levels. Biochemical, morphological, and behavioral data indicate that some of the condensation products can act as neurotoxins. Very few experiments have included an examination of long-term effects of exposure to one of these alkaloids, so the amount of information on this issue is limited. Chronic rather than acute administration of an alkaloid is more likely to mimic the pathological states in which these compounds are hypothesized to play a role. Biochemically, both the dopaminergic and serotonergic systems have been shown to be affected by chronic treatments with certain alkaloids. Progressive and long-term behavioral alterations also have been reported. Such changes may reflect an adaptation to an increase or decrease in activity of particular systems or a neurotoxic action.

Mitochondrial respiratory inhibition by N-methylated beta-carboline derivatives structurally resembling N-methyl-4-phenylpyridine.

“…Several 1,2,3,4-tetrahydro-f3Cs (THfCs) have been detected in vivo, apparently forming from cellular (PictetSpengler) condensations of indoleamines or tryptophan with aldehydes or a-keto acids (20,21). Dietary sources for THBCs are possible as well.…”

Contribution of Individual Cytochrome P450 Isozymes to theO-Demethylation of the Psychotropic β-Carboline Alkaloids Harmaline and Harmine

“…Their levels in humans are usually elevated after drinking alcohol. The association of ␤-carbolines with alcohol dependence and brain damage has been suggested (Melchior and Collins, 1982;Collins, 2002).Endogenous and exogenous ␤-carboline alkaloids were reported to exert a wide spectrum of psychopharmacological and behavioral effects in the brain (Airaksinen and Kari, 1981). Most ␤-carbolines are strong reversible inhibitors of monoamine oxidase (MAO).…”

Catechol Tetrahydroisoquinolines Enhance a-Synuclein Aggregation and Specify the Neurotoxicity to Dopaminergic Neurons

“…Also, there is a chiral c enantiomer in the C1 location of CTIQ, which is the reason of existence of (R) and (S)-enantiomer of CTIQ. In the mammalian brain, they were synthesized by an enzymatic and non-enzymatic Pictet-Spengler condensation of neuroamines with aldehydes [12]. The chemical formulae, synthesis and metabolism of common CTIQs are shown in Figure 1.…”

“…CTIQs and their derivatives can be synthesized based on different active aldehydic derivatives and DA product or its metabolites, such as 1-methyl-6,7-dihydroxyl-1,2,3,4-tetrahydroisoquinoline(Sasolinol,Sal),1-acetyl-6,7-dihydroxyl-1,2,3,4-tetrahydroisoqu-inoline (ADTIQ) and 6,7-dihydroxyl-1,2,3,4-tetrahydro-isoquinoline (norsalsolinol,norsal) [12,15,16]. These CTIQs listed above could be reacted into N-methylnorsalsolinol (NM-NorSal), N-methylsalsolinol (NM-Sal) and N-methyl-ADTIQ (NM-ADTIQ) by nitrogen methyltransferase respectively, and then generated to ion [17].…”

“…Unlike exogenous neurotoxins, CTIQs is a group of products which could be synthesized in the brain of human based on the condensation of DA and some certain aldehydes. So it is proposed that they might be the key factors involved in α-syn aggregation [10][11][12] In this review, we will describe the relationship between CTIQs and the abnormal aggregation of α-syn and try to provide a helpful insight into therapeutic approaches for PD.…”