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26. The Potential of Scopolamine as an Antidepressant in Major Depressive Disorder: A Systematic Review of Randomized Controlled Trials.

Author

Moćko, Paweł, Śladowska, Katarzyna, Kawalec, Paweł, Babii, Yana, and Pilc, Andrzej

Subjects
MENTAL depression, SCOPOLAMINE, RANDOMIZED controlled trials, ANTIDEPRESSANTS, MENTAL illness
Abstract

Major depressive disorder is one of the most severe mental disorders. It strongly impairs daily functioning, and, in extreme cases, it can lead to suicide. Although different treatment options are available for patients with depression, there is an ongoing search for novel therapeutic agents, such as scopolamine (also known as hyoscine), that would offer higher efficacy, a more rapid onset of action, and a more favorable safety profile. The aim of our study was to review the current clinical evidence regarding the use of scopolamine, a promising therapeutic option in the treatment of depression. A systematic literature search was performed using PubMed, Embase, and CENTRAL databases up to 5 June 2023. We included randomized placebo-controlled or head-to-head clinical trials that compared the clinical efficacy and safety of scopolamine in the treatment of major depressive disorder. Two reviewers independently conducted the search and study selection and rated the risk of bias for each study. Four randomized controlled trials were identified in the systematic review. The included studies investigated the use of scopolamine administered as an oral, intramuscular, or intravenous drug, alone or in combination with other antidepressants. The results indicated that scopolamine exerts antidepressant effects of varying intensity. We show that not all studies confirmed a statistically and clinically significant reduction of depressive symptoms vs. placebo. A broader perspective on scopolamine use in antidepressant treatment should be confirmed in subsequent large randomized controlled trials assessing both effectiveness and safety. Therefore, studies directly comparing the effectiveness of scopolamine depending on the route of administration are required. [ABSTRACT FROM AUTHOR]

Published
2023
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44. Design and Synthesis of New Quinazolin-4-one Derivatives with Negative mGlu 7 Receptor Modulation Activity and Antipsychotic-Like Properties.

Author

Kaczorowska, Katarzyna, Stankiewicz, Anna, Bugno, Ryszard, Paluchowska, Maria H., Burnat, Grzegorz, Brański, Piotr, Cieślik, Paulina, Wierońska, Joanna M., Milik, Mariusz, Nowak, Mateusz, Przybyłowicz, Agnieszka, Kozioł, Aneta, Hogendorf, Agata, Hogendorf, Adam S., Kalinowska-Tłuścik, Justyna, Duszyńska, Beata, Pilc, Andrzej, and Bojarski, Andrzej J.

Subjects
CHEMICAL libraries, NEURAL inhibition, QUINAZOLINONES, SOCIAL perception, SOCIAL interaction, ARIPIPRAZOLE, RISPERIDONE
Abstract

Following the glutamatergic theory of schizophrenia and based on our previous study regarding the antipsychotic-like activity of mGlu7 NAMs, we synthesized a new compound library containing 103 members, which were examined for NAM mGlu7 activity in the T-REx 293 cell line expressing a recombinant human mGlu7 receptor. Out of the twenty-two scaffolds examined, active compounds were found only within the quinazolinone chemotype. 2-(2-Chlorophenyl)-6-(2,3-dimethoxyphenyl)-3-methylquinazolin-4(3H)-one (A9-7, ALX-171, mGlu7 IC50 = 6.14 µM) was selective over other group III mGlu receptors (mGlu4 and mGlu8), exhibited satisfactory drug-like properties in preliminary DMPK profiling, and was further tested in animal models of antipsychotic-like activity, assessing the positive, negative, and cognitive symptoms. ALX-171 reverse DOI-induced head twitches and MK-801-induced disruptions of social interactions or cognition in the novel object recognition test and spatial delayed alternation test. On the other hand, the efficacy of the compound was not observed in the MK-801-induced hyperactivity test or prepulse inhibition. In summary, the observed antipsychotic activity profile of ALX-171 justifies the further development of the group of quinazolin-4-one derivatives in the search for a new drug candidate for schizophrenia treatment. [ABSTRACT FROM AUTHOR]

Published
2023
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