Novel Glutamatergic Modulators for the Treatment of Mood Disorders: Current Status

Novel Insights Into the Neurobiology of the Antidepressant Response From Ketamine Research: A Mini Review

“…Memantine proved ineffective as an antidepressant in two double-blind placebo-controlled trials ( Zarate et al, 2006b ; Smith et al, 2013 ). Similarly, rislenemdaz (also known as MK-0657), an NR2B subunit-specific NMDA receptor antagonist, failed to produce antidepressant effects in TRD, either when used as a monotherapy or in conjunction with other antidepressants ( Ibrahim et al, 2012 ; Henter et al, 2021 ). Lanicemine, an NMDA blocker with low rates of associated psychotomimetic effects, does not come near to replicating ketamine’s antidepressant effects ( Zarate et al, 2013 ; Sanacora et al, 2017 ).…”

“…Lanicemine, an NMDA blocker with low rates of associated psychotomimetic effects, does not come near to replicating ketamine’s antidepressant effects ( Zarate et al, 2013 ; Sanacora et al, 2017 ). More recently, three phase-III clinical trials of rapastinel, an NMDA receptor modulator with glycine-site partial agonist features, also failed to demonstrate antidepressant effects ( Henter et al, 2021 ). This outcome is sobering, given that pre-clinical research had demonstrated antidepressant-like effects of rapastinel in mice and rats ( Burgdorf et al, 2013 ; Yang et al, 2016 ).…”

Clinical characteristics and treatment of treatment-resistant bipolar depression

“…Σε αυτούς ανήκουν: η (ρακεμική) R,S-κεταμίνη, η (S) εσκεταμίνη, η (R)κεταμίνη (ή αρκεταμίνη), η (2R,6R)-υδροξυνορκεταμίνη [HNK], η δεξτρομεθορφάνη, ο συνδυασμός δεξτρομεθορφάνης και κινιδίνης (Nuedexta), η δευδεξτρομεθορφάνη [AVP-786], ο παράγοντας AXS-05, η δεξτρομεθαδόνη [REL-1017], το υποξείδιο του αζώτου (N 2 O), οι παράγοντες AZD6765, CLE100, AGN-241751. 68 Η αντικαταθλιπτική δράση της κεταμίνης και της εσκεταμίνης σε υπο-αναισθητικές δόσεις ερευνάται και στο πεδίο της ΔΚ. 69,70 Κλινικά διαπιστώνεται ότι η εσκεταμίνη επιφέρει βελτίωση της ΔΚ και ιδιαίτερα τα συμπτώματα της ανηδονίας και του αυτοκτονικού ιδεασμού που τη συνοδεύουν και η βελτίωση αυτή είναι μεγαλύτερη συγκριτικά με εκείνη που επιφέρουν τα συμβατικά μονοαμινεργικά αντικαταθλιπτικά.…”

The Effects of N-Acetylcysteine on the Rat Mesocorticolimbic Pathway: Role of mGluR5 Receptors and Interaction with Ethanol

“…Nonsynaptic Glu can interact with metabotropic Glu receptors (mGluRs). Group I mGluRs (mGluR1 and mGluR5) are positively linked to phospholipase C. Therefore, the direct activation of mGluR1/5 receptors results in increased phosphoinositide turnover, whereas Group II mGluRs (e.g., mGluR2 and mGluR3, among others) negatively modulate excitatory Glu transmission at the perisynaptic and postsynaptic levels through the inhibition of adenylyl cyclase [ 7 ]. Group I mGluRs are located away from synaptic zones and appear to be restricted to postsynaptic terminals [ 8 ]; Group II receptors are located both in glial cells (mGluR3) [ 9 ] and presynaptically, also away from synaptic zones (mGluR2) [ 10 ].…”

“…Group I mGluRs are located away from synaptic zones and appear to be restricted to postsynaptic terminals [ 8 ]; Group II receptors are located both in glial cells (mGluR3) [ 9 ] and presynaptically, also away from synaptic zones (mGluR2) [ 10 ]. It has been suggested that Glu has a higher affinity for mGluR2/3 than for other metabotropic receptors, such as mGluR5 [ 7 ]. Therefore, low extracellular Glu levels should preferentially activate mGluR2/3 and attenuate Glu release from the active presynaptic terminals.…”