Presence of tetrahydroisoquinoline and 1-methyl-tetrahydro-isoquinoline in foods: Compounds related to Parkinson's disease

doi:10.1016/0024-3205(88)90115-4

Life Sciences

Volume 43, Issue 4, 1988, Pages 373-378

https://doi.org/10.1016/0024-3205(88)90115-4 Get rights and content

Abstract

This is the first report confirming the presence of 1, 2, 3, 4-tetrahydroisoquinoline (TIQ) and 1-methyl-1, 2, 3, 4-tetrahydroisoquinoline (1MeTIQ) in a number of foods with a high 2-phenylethylamine content. These compounds were determined by gas chromatography-mass spectrometry. This study also confirmed that 1MeTIQ and TIQ can cross the blood-brain barrier in rat. Thus, these compounds, suspected to have relation to parkinson's disease, may accumulate in the brain from food sources.

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Cited by (101)

Design, synthesis, and biological evaluation of THIQ as antidepressive agents
2023, Bioorganic and Medicinal Chemistry Letters
7-substituted tetrahydroisoquinolines derivatives were designed, synthesized, and evaluated for neuroprotective properties. We summarized the preliminary structure activity relationships (SAR). Compound 3i was screened as a hit compound and its antidepressant activity was evaluated by employing the forced swimming test, tail suspension test. Additionally, ADMET profile (absorption, distribution, metabolism, excretion and toxicity properties) of the compound 3i was predicted in order to evaluate their lead-like properties and safety. The interaction of compound 3i bound to MAO-A was explored using molecular docking and molecular dynamics simulation. Results of biological studies revealed that the compound 3i exhibited almost equal antidepressant activity compared with magnoflorine. Compound 3i is predicted to possess good drug like properties and safety based on ADMET profile predictions. This work provides ideas for the drugs discovery of antidepressant agents.
1-Methyl-1,2,3,4-tetrahydroisoquinoline – The toxicological research on an exo/endogenous amine with antidepressant-like activity – In vivo, in vitro and in silico studies
2019, Pharmacological Reports
Citation Excerpt :
The previous studies have shown that 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) – an endogenous amine synthesized in mammalian brain but also naturally occurring in plants, variety of food and mammalian brain can easily penetrate through the blood-brain barrier [1–3].
1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) demonstrates significant neuroprotective activity. It can interact with agonistic conformation of dopamine (DA) receptors. 1MeTIQ inhibits the formation of 3,4-dihydroxyphenylacetic acid as well as production of free radicals and shifts DA catabolism toward COMT-dependent O-methylation. 1MeTIQ inhibits both MAO-A and B enzymes activity and increases neurotransmitters levels in the brain. It shows significant antidepressant-like effect in forced swim test (FST) in rats. This compound might be effective for depression therapy in a clinical setting but its success is determined not only by good efficacy, but also by an acceptable its ADMET profile. The use of combination in silico prediction with in vivoand in vitro studies greatly simplifies the search for new, safer and effectively acting drugs.
The aim of this study was to investigate the degree of histopathological changes in different rats tissues after acute and chronic administration of 1MeTIQ. Additionally, prediction of its properties in terms of absorption, distribution, metabolism, elimination and toxicity in the human body was performed.
The obtained data did not show extensive and significant toxic effects of tested substance in in vivo and in vitro studies in rats, and in silico ADMET prediction.
These results can help to discover a new effective and safe antidepressant substance and have important significance in the treatment of depression in clinic. Additionally, the use in the treatment of depression substance with neuroprotective, antioxidant and antidepressant-like effects in the CNS and existing endogenously might be also beneficial in controlling the adverse CNS inflammatory processes accompanying depression.
The mechanism of neuroprotective action of natural compounds
2017, Pharmacological Reports
Disturbance of cerebral redox homeostasis is the primary cause of human neurodegenerative disorders, such as Parkinson's disease or Alzheimer's disease. Well known experimental research demonstrates that oxidative stress is a main cause of cell death. A high concentration of reactive oxygen and nitrogen species leads to damage of a lot of proteins, lipids and also DNA. Synthetic compounds used for the treatment in the neurodegenerative diseases failed to meet the hopes they had raised and often exhibit a number of side effects. Therefore, in recent years interest in natural compounds derived from plants appears to be on the rise. This review describes a few natural compounds (1MeTIQ, resveratrol, curcumin, vitamin C and Gingko biloba) which revealed neuroprotective potential both in experimental studies and clinical trials. 1MeTIQ has a privileged position because, as opposed to the remaining compounds, it is an endogenous amine synthesized in human and animal brain. Based on evidence from research, it seems that a common protective mechanism for all the above-mentioned natural compounds relies on their ability to inhibit or even scavenge the excess of free radicals generated in oxidative and neurotoxin-induced processes in nerve cells of the brain. However, it was demonstrated that further different molecular processes connected with neurotoxicity (e.g. the inhibition of mitochondrial complex I, activation of caspase-3, apoptosis) follow later and are initiated by the reactive oxygen species. What is more, these natural compounds are able to inhibit further stages of apoptosis triggered by neurotoxins in the brain.
Antidepressant-like effect of 1,2,3,4-tetrahydroisoquinoline and its methyl derivative in animal models of depression
2017, Pharmacological Reports
Most of the currently used antidepressant drugs are monoamine-based compounds, acting by the inhibition of re-uptake or metabolism of noradrenaline (NA) and/or serotonin (5-HT), because these neurotransmitters play a key role in the pathophysiology of depression. The aim of this study was to investigate the potential antidepressant-like activity of an endogenous amine, 1,2,3,4-tetrahydroisoquinoline (TIQ) and its close derivative, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ).
The experiments were carried out on male C57BL6J mice. The antidepressant-like activity of TIQs was evaluated in the behavioral tests: the forced swim test (FST) and tail suspension test (TST) and neurochemical analysis. TIQ and 1MeTIQ were administrated in three differences doses of 10, 25 or 50 mg/kg. Imipramine (IMI; 15 or 30 mg/kg) was used as a reference drug. In the neurochemical ex vivo study, the levels of NA, 5-HT and their metabolites, the rate of monoamine metabolism and their neuronal activity in different mouse brain structures were determined by HPLC with electrochemical detection.
The results of this study have demonstrated that TIQ and 1MeTIQ produced antidepressant-like effect in the FST and TST because they significantly decreased the immobility time comparably to IMI. Biochemical data have demonstrated that administration of TIQs led to the activation of NA and 5-HT systems.
The results reported in this paper indicate that TIQ and 1MeTIQ possess a distinct antidepressant activity. In the light of these findings, we suggest that both tested compounds may be effective for the depression therapy in a clinical setting with better tolerance of side effects.
Current Status, Gaps, and Weaknesses of the Mechanism of Selective Dopaminergic Toxicity of MPTP/MPP<sup>+</sup>
2017, Advances in Molecular Toxicology
Among Parkinson's disease (PD) toxin models, MPTP/MPP⁺ has been the most popular, extensively characterized, and widely used to identify the cellular mechanisms associated with the selective degeneration of dopaminergic neurons in PD. A number of recent studies have found some gaps and weaknesses in the generally accepted mechanism especially with regard to the selective dopaminergic toxicity of the model. Accumulating evidence suggests that the inherent physiological predisposition of dopaminergic neurons to generate high oxidative stress, especially when exposed to various environmental and genetic factors and their inability to cope with these conditions effectively, could contribute to their selective destruction. However, the current models for the selective dopaminergic toxicity of MPTP/MPP⁺ have not taken into account the unique susceptibilities of these neurons. The focus of this chapter is to discuss the discovery, current status, gaps, and weaknesses of the mechanism of the specific dopaminergic toxicity of the MPTP/MPP⁺ model.
N-methyltetrahydropyridines and pyridinium cations as toxins and comparison with naturally-occurring alkaloids
2016, Food and Chemical Toxicology
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium cation (MPP⁺) are selective dopaminergic neurotoxins producing Parkinsonism. MPTP is activated by monoamine oxidase-B (MAO-B) to MPP⁺ that inhibits mitochondrial function. Molecules resembling MPTP which afford pyridinium cations are also neurotoxins. The herbicide paraquat (a bipyridinium dication) and the naturally-occurring β-carboline and isoquinoline alkaloids are structural analogues of MPTP/MPP⁺. Paraquat generates reactive oxygen species (ROS) producing neurotoxicity by a mechanism that differs from MPTP/MPP⁺. Human exposure to PQ is increasingly associated with neurodegeneration. Tetrahydro-β-carbolines (THβCs), β-carbolines (βCs) and tetrahydroisoquinolines (TIQ_s) are bioactive compounds occurring in foods and the human body. They are not MPTP-like toxins and do not appear to induce neurotoxicity at normal levels of exposure. Among TIQs, endogenous dopamine-derived TIQs (i.e. salsolinol) and 1-benzyl-TIQ are toxic through ROS generation. In contrast, β-carbolinium (βC⁺s) and isoquinolinium cations (IQ⁺s) are neurotoxicants resembling MPP⁺ although they are less potent and selective. βC⁺s and IQ⁺s have been detected in the human brain but their toxicological significance remains unknown. THβCs/βCs and TIQs are activated to toxic cations by N-methyltransferases (NMT) and/or heme peroxidases and are metabolized by cytochrome P450 enzymes. Remarkably, recent findings suggest, instead, that βCs and TIQs are neuroprotectants and neurorestorative, raising the interest of these molecules.

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Presence of tetrahydroisoquinoline and 1-methyl-tetrahydro-isoquinoline in foods: Compounds related to Parkinson's disease

Abstract

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

Biomed. Res.

Clin. Neuropharmacol.

Eur. Neurol.

Neurosci. Lett.