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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

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

Edyta Możdżeń, Izabela Babińska, Jacek Wójcikowski, Lucyna Antkiewicz-Michaluk

Pharmacol Rep. 2019 Dec;71(6):1140-1146.

PMID: 31655278

Abstract:

Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP4965097	1-Methyl-1,2,3,4-tetrahydroisoquinoline		4965-09-7	Price

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