NMDA Receptor Antagonists for Treatment of Depression

Ateş‐Alagöz, Zeynep; Adejare, Adeboye

doi:10.3390/ph6040480

Cited by 52 publications

(32 citation statements)

References 56 publications

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“…NMDA receptor antagonists exemplify an important pharmacological class that provides promising pharmacological tools. They are used or are being investigated in a number of therapeutic areas including general anesthesia, neuroprotection, management of neuropathic pain and depression . Issues linked with clinical tolerability remain challenging for clinical development of this promising pharmacological class …”

Section: Introductionmentioning

confidence: 87%

Syntheses and analytical characterizations of N‐alkyl‐arylcyclohexylamines

Wallach

Colestock

Cicali

et al. 2015

Drug Testing and Analysis

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Abstract:The rise in new psychoactive substances that are available as 'research chemicals' (RCs) remains a significant forensic and legislative challenge. A number of arylcyclohexylamines have attracted attention as RCs and continued to be encountered, including 3-MeO-PCP, 3-MeO-PCE and 3-MeO-PCPr. These compounds are commonly perceived as ketamine-like dissociative substances and are believed to act predominantly via antagonism of the N-methyl-D-aspartate (NMDA) receptor. To aid in the identification of newly emerging substances the syntheses of fifteen Nalkyl-arylcyclohexylamines are described. Analytical characterizations were performed via gas chromatography and high performance liquid chromatography coupled to multiple forms of mass spectrometry as well as nuclear magnetic resonance spectroscopy, ultraviolet diode array detection and infrared spectroscopy. The series consisted of the N-alkyl derivatives (N-methyl, N-ethyl, N-propyl) of phenyl-substituted and isomeric 2-, 3-and 4-methoxy phenylcyclohexylamines, as well as the N-alkyl derivatives obtained from a 3-methylphenyl and 2-thienyl moiety. In addition to the presentation of a range of previously unreported data, it was also found that positional isomers of aryl methoxyl-substituted arylcyclohexylamines were readily distinguishable under a variety of analytical conditions. Running title: Characterization of N-alkyl-arylcyclohexylamines AbstractThe rise in new psychoactive substances that are available as 'research chemicals' (RCs) remains a significant forensic and legislative challenge. A number of arylcyclohexylamines have attracted attention as RCs and continued to be encountered, including 3-MeO-PCP, 3-MeO-PCE and 3-MeO-PCPr. These compounds are commonly perceived as ketamine-like dissociative substances and are believed to act predominantly via antagonism of the N-methyl-D-aspartate (NMDA) receptor. To aid in the identification of newly emerging substances the syntheses of fifteen N-alkyl-arylcyclohexylamines are described. Analytical characterizations were performed via gas chromatography and high performance liquid chromatography coupled to multiple forms of mass spectrometry as well as nuclear magnetic resonance spectroscopy, ultraviolet diode array detection and infrared spectroscopy. The series consisted of the N-alkyl derivatives (N-methyl, Nethyl, N-propyl) of phenyl-substituted and isomeric 2-, 3-and 4-methoxy phenylcyclohexylamines, as well as the N-alkyl derivatives obtained from a 3-methylphenyl and 2-thienyl moiety. In addition to the presentation of a range of previously unreported data, it was also found that positional isomers of aryl methoxylsubstituted arylcyclohexylamines were readily distinguishable under a variety of analytical conditions.

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Section: Introductionmentioning

confidence: 87%

Syntheses and analytical characterizations of N‐alkyl‐arylcyclohexylamines

Wallach

Colestock

Cicali

et al. 2015

Drug Testing and Analysis

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“…NMDARs have received special attention because of their critical role in psychiatric disorders [236]. Antidepressant-like effects have been demonstrated by several types of NMDAR antagonists in different animal models [237].…”

Section: Tbi As a Risk Factor For Neurological Disease: Role Of Nmmentioning

confidence: 99%

Role of NMDA Receptor-Mediated Glutamatergic Signaling in Chronic and Acute Neuropathologies

2016

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N-Methyl-D-aspartate receptors (NMDARs) have two opposing roles in the brain. On the one hand, NMDARs control critical events in the formation and development of synaptic organization and synaptic plasticity. On the other hand, the overactivation of NMDARs can promote neuronal death in neuropathological conditions. Ca2+ influx acts as a primary modulator after NMDAR channel activation. An imbalance in Ca2+ homeostasis is associated with several neurological diseases including schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. These chronic conditions have a lengthy progression depending on internal and external factors. External factors such as acute episodes of brain damage are associated with an earlier onset of several of these chronic mental conditions. Here, we will review some of the current evidence of how traumatic brain injury can hasten the onset of several neurological conditions, focusing on the role of NMDAR distribution and the functional consequences in calcium homeostasis associated with synaptic dysfunction and neuronal death present in this group of chronic diseases.

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“…[ 47 ] Recent studies on laboratory animals revealed that the administration of L-arginine has potential therapeutic importance, including anticonvulsant, anxiolytic, and antidepressant-like actions. [ 48 49 50 ]…”

Section: Discussionmentioning

confidence: 99%

“…The therapeutic effects of L-arginine may result from different mechanisms including inhibition of NOS,[ 51 ] oxygen radical scavenging,[ 52 ] blocking of N-methyl-D-aspartate (NMDA) receptors,[ 48 49 50 ] and protection against mitochondrial membrane potential collapse. [ 53 ] However, the sequence of events leading to the protective effects of L-arginine against cell damage has not been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…[ 59 ] There is increasing evidence of the beneficial effects of L-arginine blockades NMDA receptors, against different insults of the CNS. [ 48 49 50 ] Previous studies have also demonstrated that MPTP decreases glutamate uptake by astrocytes in cell culture. [ 60 ] Therefore, one possible mechanism by which L-arginine may exert beneficial effects against MPTP neurotoxicity may be due to the modulation of glutamate reuptake into neural cells.…”

Section: Discussionmentioning

confidence: 99%

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Beneficial effects of L-arginine on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neuronal degeneration in substantia nigra of Balb/c mice

et al. 2016

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Background:L-arginine has been recently investigated and proposed to reduce neurological damage after various experimental models of neuronal cellular damage. In this study, we aim to evaluate the beneficial effects of L-arginine administration on the numerical density of dark neurons (DNs) in the substantia nigra pars compacta (SNc) of Balb/c mice subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration.Materials and Methods:Male Balb/c mice were randomly divided into 4 groups (n = 7 each): MPTP only; saline only (control); MPTP + L-arginine; and L-arginine only. The animals were infused intranasally with a single intranasal administration of the proneurotoxin MPTP (1 mg/nostril). L-arginine (300 mg/kg) was administrated intraperitoneally once daily for 1-week starting from 3 days after MPTP administration. Cavalieri principle method was used to estimate the numerical density of DNs in the SNc of different studied groups.Results:Twenty days following MPTP administration, the number of DNs was significantly increased when compared to sham-control and L-arginine-control groups (P < 0.05). Nevertheless, our results showed that L-arginine administration significantly decreased the numerical density of DNs in SNc of mice.Conclusion:This investigation provides new insights in experimental models of Parkinson’s disease, indicating that L-arginine represents a potential treatment agent for dopaminergic neuron degeneration in SNc observed in Parkinson’s disease patients.

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NMDA Receptor Antagonists for Treatment of Depression

Cited by 52 publications

References 56 publications

Syntheses and analytical characterizations of N‐alkyl‐arylcyclohexylamines

Syntheses and analytical characterizations of N‐alkyl‐arylcyclohexylamines

Role of NMDA Receptor-Mediated Glutamatergic Signaling in Chronic and Acute Neuropathologies

Beneficial effects of L-arginine on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neuronal degeneration in substantia nigra of Balb/c mice

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