Biomolecules
August 24, 2026
Agnieszka Pałucha-Poniewiera
The use of animal models to study mental illnesses, such as depression, requires proper standardization and extensive expertise. Achieving good construct, face, and predictive validity in depression models is quite challenging. Currently, only a few environmental models, mostly based on chronic stress, and a limited number of genetic models fulfill these criteria. In the quest for new...
Cells
December 11, 2025
Agnieszka Pałucha-Poniewiera
Since the introduction of the NMDA receptor antagonist (S)-ketamine for depression therapy, it has become evident that the glutamatergic hypothesis of depression, proposed over 20 years ago, was justified and based on solid foundations. A significant breakthrough with this drug is its ability to produce a rapid and relatively long-lasting antidepressant effect in patients who are resistant to...
The International Journal of Neuropsychopharmacology
August 1, 2025
Yana Babii, C. Barbara, Dorota Bederska‐łojewska et al.
Abstract Background Numerous data indicates that hallucinogens from various groups such as ketamine, scopolamine or psilocybin exert rapid antidepressant effects in both preclinical and clinical studies. Group II glutamate (mGlu) metabotropic receptor antagonists also show rapid antidepressant efficacy in animal studies, moreover we have shown that mGluR2/3 antagonist, LY341495 is able to...
Psychopharmacology
May 8, 2025
Agnieszka Pałucha-Poniewiera, Anna Rafało-Ulińska, Agata Faron-Górecka et al.
1 citation
(S)-Ketamine, which is used to treat depression, has significant undesirable effects and has potential for abuse. A safe alternative to (S)-ketamine is (R)-ketamine. The relationship between (R)-ketamine and the mGlu5 receptor is unknown, although screening tests indicate the possibility of potentiation of the antidepressant effect of (R)-ketamine by the mGlu5 receptor negative allosteric...
Pharmacological reports : PR
June 1, 2024
Agnieszka Pałucha-Poniewiera, Anna Rafało-Ulińska, Michal Santocki et al.
8 citations
Partial negative allosteric modulators (NAM) of the metabotropic glutamate 5 (mGlu5) receptor are an excellent alternative to full antagonists and NAMs because they retain therapeutic effects and have a much broader therapeutic window. Here, we investigated whether partial mGlu5 NAM, 2-(2-(3-methoxyphenyl)ethynyl)-5-methylpyridine (M-5MPEP), induced a fast and sustained antidepressant-like...
Pharmaceuticals
February 1, 2023
Agnieszka Pałucha-Poniewiera, B. Bobula, Anna Rafało-Ulińska
(S)-Ketamine is the first rapid-acting antidepressant drug (RAAD) introduced for the treatment of depression. However, research is still being carried out on the search for further RAADs that will be not only effective but also safe to use. Recent data have indicated that the combined administration of (R)-ketamine and the mGlu2/3 receptor antagonist LY341495 (mixRL) induces rapid and sustained...
Pharmacology, Biochemistry and Behavior
August 1, 2022
Agnieszka Pałucha-Poniewiera
MGlu2/3 receptor antagonists produce antidepressant-like effects in animal models of depression. A number of mechanisms responsible for these actions are convergent to the mechanism of the fast antidepressant-like effect of ketamine. Furthermore, the data indicate that ketamine effect is related to the action of mGlu2 receptors and may be reduced by their agonists. The above facts became the...
Pharmaceuticals
January 21, 2022
A. Rafało-Ulińska, P. Brański, A. Pałucha-Poniewiera
Ketamine is an effective, rapid-acting antidepressant drug (RAAD), but it induces side effects. To overcome these challenges, attempts have been made to use safer enantiomer ((R)-ketamine) or mGlu2/3 receptor antagonists, which induce ketamine-like effects and enhance its action. Here, we propose combining these two strategies to investigate the antidepressant-like effects of low doses of two...
Behavioural Brain Research
October 1, 2021
Anna Rafało-Ulińska, Agnieszka Pałucha-Poniewiera
46 citations
(S)-ketamine has been approved as a rapid-acting antidepressant drug (RAAD). Although ketamine has an advantage over classic antidepressants (ADs) due to its rapid action, it remains a controversial drug due to its undesirable effects. Behavioral studies indicate that another enantiomer of ketamine, namely, (R)-ketamine, has been proposed as a safer but still effective RAAD. However, these...
Progress in Neuro-psychopharmacology and Biological Psychiatry
January 2, 2021
Agnieszka Pałucha-Poniewiera, K. Podkowa, Anna Rafało-Ulińska
Ketamine produces a rapid antidepressant effect, but its use can be associated with serious side effects. Hence, other therapeutic options that will allow us to obtain a quick and safe antidepressant effect by modulating glutamatergic transmission are needed. Antagonists of mGlu2/3 receptors, which share some mechanisms of action with ketamine, may be good candidates to obtain this effect....
Behavioural Pharmacology
September 1, 2019
Agnieszka Pałucha-Poniewiera, K. Podkowa, Andrzej Pilc
Ketamine has been shown to induce a rapid antidepressant effect on patients with depression. In many animal models, both rapid and sustained antidepressant activities were also found in response to an antagonist of group II metabotropic glutamate receptors, LY341495, and its mechanism of action seemed to be similar in many ways to the action of ketamine. It has also been found that LY341495...