Morpholine derivatives as potential agents for neurological manifestations of nervous system diseases

Prikhodko, Veronika A.; Александровна, Приходько Вероника; Sysoev, Yuriy I.; Игоревич, Сысоев Юрий; Оковитый, С. В.; Владимирович, Оковитый Сергей

doi:10.17816/phf21381

Cited by 3 publications

(1 citation statement)

References 103 publications

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“…Known centrally acting morpholine-containing compounds include stimulants/anorectics (phenmetrazine and analogues); dissociative anesthetics (phencyclidine analogues); anticonvulsants (imepitoin); antiemetics (azasetron, aprepitant, and analogues); antidepressants (reboxetine, moclobemide, and viloxazine); tranquilizers (trimetozine); antipsychotics (molindone); central analgesics (pravadoline and analogues); opioids (dextromoramide, morpheridine, phenadoxone, and pholcodine); non-opioid central antitussives (morclofone and pentethylcyclanone); and antiparkinsonian (foliglurax and tozadenant), neuroprotective (WIN 55,212-2 and PRE-084), and nootropic (CX717 and A-349,821) agents [ 5 ]. Potential indications for morpholine-based drugs may, in turn, include Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, multiple sclerosis, lateral amyotrophic sclerosis, traumatic brain injury, and ischemic stroke [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Chromone-Containing Allylmorpholines Induce Anxiolytic-like and Sedative Effects in Adult Zebrafish

et al. 2022

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Chromone-containing allylmorpholines (CCAMs) are a novel class of compounds that have demonstrated acetyl- and butyryl-cholinesterase-inhibiting and N-methyl-D-aspartate (NMDA) receptor-blocking properties in vitro, but their in vivo pharmacological activity remains underexplored. In this work, we evaluated the psychotropic activity of five different CCAMs (1 (9a), 2 (9j), 3 (9l), 4 (33a), and 5 (33b)) using the novel tank test (NTT) and light/dark box (LDB) test in adult zebrafish. The CCAMs were screened in the NTT at a range of concentrations, and they were found to induce a dose-dependent sedative effect. Compound 4 (33a) was also evaluated using the LDB test, and it was found to have anxiolytic-like properties at low concentrations. To assess the potential contribution of the glutamate and cholinergic mechanisms in the effects of the CCAMs, we conducted experiments with pre-exposure to putative antagonists, NMDA and biperiden. Neither biperiden nor NMDA were able to diminish or cancel the effects of the CCAMs, countering the in vitro data obtained in previous studies. The apparent discrepancy could be related to the specifics of CCAM metabolism or to the interspecies differences between the putative target proteins, possibly due to the relatively low identity percentage of their sequences. Although further research in mammals is required in order to establish their pharmacological properties, novel CCAMs may represent an appealing group of psychoactive drug candidates.

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Section: Introductionmentioning

confidence: 99%

Novel Chromone-Containing Allylmorpholines Induce Anxiolytic-like and Sedative Effects in Adult Zebrafish

et al. 2022

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Evaluation of the neuroprotective activity of a new allylmorpholine derivative in a rat model of traumatic brain injury

Prikhodko

Kan

Sysoev

et al. 2021

Razrabotka i registraciâ lekarstvennyh sredstv

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Introduction. The search for and development of new drugs capable of reducing the severity of neurological deficit in traumatic brain injury are a critical task for investigational pharmacology. Chromone-containing allylmorpholines are a new group of neuroprotective drug candidates that have been shown to inhibit acetylcholinesterase and butyrylcholinesterase, and block N-methyl-D-aspartate receptors in vitro.Aim. This study aimed to evaluate the neuroprotective activity of the allylmorpholine derivative (E)-4-[3-(8-bromo-6-methyl-4-oxo-4H-chromen- 3-yl)-1-cyclohexylallyl]morpholin-4-ium chloride (33b) in vivo using a rat model of traumatic brain injury.Materials and methods. Traumatic brain injury was induced using the controlled cortical impact model. The allylmorpholine derivative was administered intraperitoneally at 1, 10, or 50 mg × kg-1 b.w. at 1 h after trauma induction, and then daily for the next 6 d. The neurological deficit was assessed using the Limb Placing, Open Field, Elevated Plus Maze, Beam Walking, and Cylinder tests.Results and discussion. At all doses administered, the allylmorpholine derivative had no positive effect on the motor function or exploratory behavior following traumatic brain injury. In the Elevated Plus Maze, 10 mg × kg-1 b.w. of the compound further suppressed exploratory behaviour in the injured animals, which appears to be consistent with its sedative properties observed previously in zebrafish.Conclusion. Despite the previously described in vitro affinity of allylmorpholines towards several molecular targets crucial for the pathogenesis of brain trauma and posttraumatic functional recovery, an allylmorpholine derivative had no neuroprotective effect in a rat model of traumatic brain injury in this study. These results further emphasize the importance of in vivo evaluation of potential neuroprotective drug candidates.

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Overview of Piperidine and Morpholine Derivatives as Promising Sources of Biologically Active Compounds (Review)

Khamitova

Berillo

2023

Razrabotka i registraciâ lekarstvennyh sredstv

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Introduction. The search for new, effective and safe pharmacologically active substances remains an urgent task in the field of pharmacy. Many compounds of the piperidine and morpholine series are widely used in medical practice and belong to an important group of biologically active compounds. An informational, literature search on the synthesis of new derivatives of piperidine and morpholine was carried out. The article summarizes the results of studies of new derivatives of piperidine and morpholine as potential sources of biologically active substances.Text. The review is devoted to the relationship between the pharmacological activity of the N-derivatives of piperidine and morpholine in relation to various biological targets and the structure of the substance, the importance of the piperidine and morpholine rings in the design and development of drugs is highlighted. Piperidine and morpholine are considered as prerogative structures not only for increasing activity, but also for obtaining biological substances with desired therapeutic properties and improved pharmacokinetics.Conclusion. The literature review shows the current trend towards the study of morpholine and piperidine derivatives, reveals their high pharmacophore activity. The review will provide researchers with the necessary knowledge base to make chemical structural changes to the structures of drug leaders to enhance pharmacological activities.

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Morpholine derivatives as potential agents for neurological manifestations of nervous system diseases

Cited by 3 publications

References 103 publications

Novel Chromone-Containing Allylmorpholines Induce Anxiolytic-like and Sedative Effects in Adult Zebrafish

Novel Chromone-Containing Allylmorpholines Induce Anxiolytic-like and Sedative Effects in Adult Zebrafish

Evaluation of the neuroprotective activity of a new allylmorpholine derivative in a rat model of traumatic brain injury

Overview of Piperidine and Morpholine Derivatives as Promising Sources of Biologically Active Compounds (Review)

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