Article
Biochemistry & Molecular Biology
Vittorio Canale, Magdalena Kotanska, Anna Dziubina, Matylda Stefaniak, Agata Siwek, Gabriela Starowicz, Krzysztof Marciniec, Patryk Kasza, Grzegorz Satala, Beata Duszynska, Xavier Bantreil, Frederic Lamaty, Marek Bednarski, Jacek Sapa, Pawel Zajdel
Summary: The study designed and synthesized a series of dual-acting ligands arylsulfonamide derivatives of dihydrobenzofuranoxy)ethyl piperidines, with compound 8 showing potential for treating depressive symptoms and high selectivity. By targeting both alpha(2)-adrenoceptors and 5-HT7 receptors, these compounds could be potential candidates for future antidepressants.
Review
Pharmacology & Pharmacy
Christiane Brandwein, Cathalijn H. C. Leenaars, Laura Becker, Natascha Pfeiffer, Ana -Maria Iorgu, Melissa Hahn, Gaia A. Vairani, Lars Lewejohann, Andre Bleich, Anne S. Mallien, Peter Gass
Summary: This systematic mapping review provides a comprehensive overview of the evolution and commonly used set-ups of the Porsolt Forced Swim Test in rats. By offering detailed technical aspects and a list of existing publications, it enhances the reproducibility and comparability of this experiment, aiming to reduce animal usage and unnecessary replication.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Mohammed H. Elkomy, Fatma I. Abo El-Ela, Randa Mohammed Zaki, Omar A. Alsaidan, Mohammed Elmowafy, Ameeduzzafar Zafar, Khaled Shalaby, Mohamed A. Abdelgawad, Hany A. Omar, Rania Salama, Hussein M. Eid
Summary: This study developed and optimized a drug-loaded thermosensitive gel for intranasal administration to combat depression. The results demonstrated that compared to other formulations, this thermosensitive gel significantly improved behavioral performance and alleviated neural tissue changes in depressed rats. Further research is needed to determine its effectiveness in humans.
Article
Neurosciences
Josh Allen, Raquel Romay-Tallon, Milann A. Mitchell, Kyle J. Brymer, Jenessa Johnston, Carla L. Sanchez-Lafuente, Graziano Pinna, Lisa E. Kalynchuk, Hector J. Caruncho
Summary: Chronic stress is a significant risk factor for depression. Reelin protein can rapidly restore depressive-like behavior and neurochemical abnormalities induced by chronic stress through intravenous injections.
Article
Neurosciences
Karline C. Rodrigues, Cristiani F. Bortolatto, Ketlyn P. da Motta, Renata L. de Oliveira, Jaini J. Paltian, Roberta Kruger, Silvane S. Roman, Silvana P. Boeira, Diego Alves, Ethel Antunes Wilhelm, Cristiane Luchese
Summary: The study showed that 4-PSQ therapy improved hypothalamic obesity-related parameters, as well as psychiatric symptoms, cognitive impairment, and neurochemical alterations found in obese rats.
PSYCHOPHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Emily R. Trunnell, Constanca Carvalho
Summary: Despite the prevalence of treatment-resistant depression, many pharmaceutical companies have abandoned the development of new antidepressants due to low quality preclinical tests, such as over-reliance on animal behavioral screens like the forced swim test (FST). A retrospective review found that out of 109 compounds tested in the FST, only 28% were explored for antidepressant effects in humans, and only three showed potential efficacy, but are not approved for treating depression. This suggests that the FST may not be a useful screening tool for identifying novel antidepressants.
DRUG DISCOVERY TODAY
(2021)
Article
Neurosciences
A. G. Sartim, J. Marques, K. M. Silveira, P. H. Gobira, F. S. Guimaraes, G. Wegener, S. R. Joca
Summary: The study found that CBD can exhibit antidepressant effects without causing hyperactivity, and it can also inhibit the psychostimulant effects induced by ketamine. The combined administration of CBD and ketamine may be a promising therapeutic strategy for achieving antidepressant effects while reducing unwanted side effects.
Review
Neurosciences
Marc L. Molendijk, E. Ronald de Kloet
Summary: The immobility response in the forced swim test is not considered a rodent model of depression, but it can predict a compound's antidepressant potential to some extent. Despite some papers labeling immobility as depression-like behavior, the perspective on this issue varies among different countries.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2022)
Article
Behavioral Sciences
Mareli Roets, Linda Brand, Stephan F. Steyn
Summary: During the peripartum period, women are at an increased risk of developing perinatal distress. Animal studies have shown that pregnancy can alter the bio-behavioural profile of rats, and postpartum stressors can exacerbate these effects. These findings suggest that pregnancy influences postpartum behaviour in a strain-dependent manner.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Article
Behavioral Sciences
Kyle J. Brymer, Erin Y. Kulhaway, John G. Howland, Hector J. Caruncho, Lisa E. Kalynchuk
Summary: Repeated corticosterone injections in rats lead to cognitive deficits and depression-like behavior, highlighting the importance of considering cognitive impairments in assessing depression. Corticosterone significantly affects body weight, immobility in the forced swim test, startle amplitudes, and object recognition memory, suggesting a complex phenotype induced by chronic stress.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Plant Sciences
Taiwo G. Olubodun-Obadun, Ismail O. Ishola, Timisola P. Adesokan, Blessing O. Anih, Olufunmilayo O. Adeyemi
Summary: This study investigates the antidepressant and anxiolytic effects of ethanol seed extract of Cajanus cajan in mice. The extract shows potential in treating anxiety and other neurological disorders, possibly through the involvement of monoaminergic systems and GABA receptors.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Behavioral Sciences
Yixue Qin, Haoxuan Li, Yuqi Zhang, Jun-Li Cao, Wenxin Zhang, Hongxing Zhang
Summary: The addition of retigabine as an adjunctive treatment enhances the antidepressant effect of ketamine, allowing for a lower dose of ketamine to be effective in the forced swim test. Simultaneous administration of retigabine with ketamine significantly improves the duration and effectiveness of ketamine's antidepressant effect.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2023)
Article
Biochemistry & Molecular Biology
Joanna Kowalczyk, Modestos Nakos-Bimpos, Alexia Polissidis, Christina Dalla, Nikolaos Kokras, Krystyna Skalicka-Wozniak, Barbara Budzynska
Summary: The study aimed to investigate the sex-dependent effects of imperatorin on antidepressant effects. The results showed that only males responded to imperatorin treatment and exhibited antidepressant effects, while serotonin levels in the prefrontal cortex of females decreased. This suggests that imperatorin may have antidepressant potential, but only in males.
Article
Neurosciences
Arnab Nandi, Garima Virmani, Aatmika Barve, Swananda Marathe
Summary: FST and TST are common behavioral tests for screening antidepressant drugs and assessing non-motor symptoms in movement disorder animal models. Manual analysis of these tests is time-consuming with large variability, but the open-source program DBscorer provides automated and unbiased analysis, allowing for a nuanced understanding of behavioral despair expression.
Article
Integrative & Complementary Medicine
Sun Dan-chen, Wang Ran-ran, Xu Hao, Zhu Xue-hui, Sun Yan, Qiao Shi-qing, Qiao Wei
Summary: This study investigated the pharmacodynamic material basis, mechanism of actions, and targeted diseases of Salicornia europaea L. (SE) using the network pharmacology method. Pharmacological experiments verified the antidepressant-like effect of SE extract and suggested that it may regulate the Nrf2-ARE pathway and increase levels of dopamine and corticosterone in the hippocampus and cortex.
CHINESE JOURNAL OF INTEGRATIVE MEDICINE
(2022)
Article
Clinical Neurology
Natalia Malikowska-Racia, Joanna Golebiowska, Agnieszka Nikiforuk, Shaun Yon-Seng Khoo, Piotr Popik
Summary: The antidepressant effects of (S)-ketamine have revolutionized depression treatment, but it also produces psychotomimetic effects. A recent study found that (S)-ketamine leads to time underestimation, while (R)-ketamine does not affect timing. The study evaluated the antidepressant effects and timing-related actions of (R)- and (S)-ketamine, as well as fluoxetine, in male rats. The results showed that (S)-ketamine and fluoxetine had similar antidepressant effects, while (R)-ketamine only affected reinforcement rate and peak location without impacting timing.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Joanna Jastrzebska, Wladyslawa Anna Daniel
Summary: Cytochrome P450 is involved in the metabolism of drugs, substances of abuse, and endogenous substrates. Cocaine affects the dopaminergic system and may also alter the regulation of cytochrome P450 during the addiction process. The effects of cocaine on liver cytochrome P450 enzymes depend on various factors and can lead to hepatotoxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Wojciech Pietrus, Rafal Kurczab, Dawid Warszycki, Andrzej J. J. Bojarski, Jurgen Bajorath
Summary: In this study, a total of 898 F-containing isomeric analog sets were identified and analyzed for structure-activity relationship (SAR) in the ChEMBL database. The results showed significant differences in affinity for some isomeric compounds against different aminergic GPCRs, and the change of fluorine position could lead to a significant change in potency. Additionally, a computational workflow was proposed to score the fluorine positions in the molecule.
Article
Biochemistry & Molecular Biology
Vittorio Canale, Wojciech Trybala, Severine Chaumont-Dubel, Paulina Koczurkiewicz-Adamczyk, Grzegorz Satala, Ophelie Bento, Klaudia Blicharz-Futera, Xavier Bantreil, Elzbieta Pekala, Andrzej J. Bojarski, Frederic Lamaty, Philippe Marin, Pawel Zajdel
Summary: In addition to the canonical Gs adenylyl cyclase pathway, the serotonin type 6 receptor (5-HT6R) recruits additional signaling pathways that control cognitive function, brain development, and synaptic plasticity in an agonist-dependent and independent manner. The development of biased ligands with different functional profiles at specific 5-HT6R-elicited signaling pathways may provide a novel therapeutic perspective in neurodegenerative and psychiatric diseases. A newly synthesized compound 3g exhibits neutral antagonist activity at the 5-HT6R-operated Gs signaling and inverse agonist activity at the Cdk5 pathway, making it a promising biased ligand to investigate the role of these signaling pathways in neurodegenerative diseases.
Article
Chemistry, Medicinal
Anna Partyka, Katarzyna Gorecka, Joanna Gdula-Argasinska, Natalia Wilczynska-Zawal, Magdalena Jastrzebska-Wiesek, Anna Wesolowska
Summary: Patients taking antipsychotic drugs have a higher likelihood of developing metabolic syndrome, characterized by abdominal obesity, elevated glucose levels, and dyslipidemia. Current treatments for the metabolic side effects of antipsychotic drugs are not satisfactory. Ligands of the serotonin 6 receptor may offer a promising supplement to antipsychotic therapy. This study examined the effects of different antipsychotic drugs alone and in combination with a selective 5-HT6 agonist or antagonist on weight gain, food intake, lipid profile, glucose level, and adipose and gastrointestinal hormones in rats.
Article
Chemistry, Medicinal
Vittorio Canale, Joanna Czekajewska, Karolina Klesiewicz, Monika Papiez, Agata Kuziak, Karolina Witek, Kamil Piska, Dagmara Niemiec, Patryk Kasza, Elzbieta Pekala, Joanna Empel, Magdalena Tomczak, Elzbieta Karczewska, Pawel Zajdel
Summary: The increasing resistance of bacteria to antibiotics necessitates the development of new effective antimicrobial agents. Through screening, compound 44 was identified to have promising antibacterial activity against drug-resistant Gram-positive bacteria, including MRSA and VREfm. However, it showed no activity against Gram-negative bacteria.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Krzysztof Marciniec, Zuzanna Rzepka, Elwira Chrobak, Stanislaw Boryczka, Malgorzata Latocha, Dorota Wrzesniok, Artur Beberok
Summary: Cancer cells regulate their metabolism for growth and division. PKM2, a key glycolytic enzyme, is involved in cancer metabolism and is considered a target for cancer treatment. In this study, new compounds were designed and synthesized to modulate PKM2 activity. Compound 9a was found to effectively reduce pyruvate levels in lung cancer cells and exhibit selective cytotoxicity. These findings suggest a potential for developing novel analogs for cancer treatment.
Article
Biochemistry & Molecular Biology
Nazarine Mokhtar, Marcin Drop, Florian Jacquot, Sylvain Lamoine, Eric Chapuy, Laetitia Prival, Youssef Aissouni, Vittorio Canale, Frederic Lamaty, Pawel Zajdel, Philippe Marin, Stephane Doly, Christine Courteix
Summary: Diabetic neuropathy can cause chronic pain and associated cognitive deficits. This study found that 5-HT6 receptor inverse agonists and rapamycin can alleviate mechanical hyperalgesia and cognitive deficits in a rat model of diabetic neuropathic pain. The 5-HT6 receptor ligands also showed efficacy in reducing tactile allodynia in other types of neuropathic pain. In addition, disrupting the interaction between 5-HT6 receptors and mTOR can alleviate both painful and cognitive symptoms in diabetic rats. Targeting the constitutive activity of 5-HT6 receptors or the 5-HT6 receptor-mTOR interaction could be valuable strategies for treating diabetic neuropathic pain and cognitive co-morbidities.
Article
Chemistry, Medicinal
Katarzyna Grychowska, Uriel Lopez-Sanchez, Mathieu Vitalis, Geoffrey Canet, Grzegorz Satala, Agnieszka Olejarz-Maciej, Joanna Golebiowska, Rafal Kurczab, Wojciech Pietrus, Monika Kubacka, Christophe Moreau, Maria Walczak, Klaudia Blicharz-Futera, Xavier Bantreil, Gilles Subra, Andrzej J. Bojarski, Frederic Lamaty, Carine Becamel, Charleine Zussy, Severine Chaumont-Dubel, Piotr Popik, Hugues Nury, Philippe Marin, Laurent Givalois, Pawel Zajdel
Summary: The multifactorial origin and neurochemistry of Alzheimer's disease (AD) call for the development of multitarget treatment strategies. This study reports a first-in-class triple acting compound that targets serotonin type 6 and 3 receptors (5-HT-Rs) and monoamine oxidase type B (MAO-B) as an approach for treating AD.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Clinical Neurology
Natalia Malikowska-Racia, Maciej Koniewski, Joanna Golebiowska, Piotr Popik
Summary: This study examined the immediate and sustained antidepressant-like effects of psilocybin and LSD in rats. The results showed that psilocybin had an acute effect, but neither drug demonstrated long-term antidepressant-like effects.
JOURNAL OF PSYCHOPHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Anna Haduch, Ewa Bromek, Wojciech Kuban, Agnieszka Basinska-Ziobron, Przemyslaw Danek, Natalia Alenina, Michael Bader, Wladyslawa Daniel
Summary: The depletion of brain serotonin in aging rats results in decreased mRNA and protein levels of key liver drug-metabolizing CYP enzymes, but increased enzyme activities. This suggests that brain serotonin has a regulatory role in liver CYP function, affecting drug metabolism in mature and senescent animals differently.
PHARMACOLOGICAL REPORTS
(2023)
Article
Pharmacology & Pharmacy
Katarzyna Szczepanska, Andrzej J. J. Bojarski, Piotr Popik, Natalia Malikowska-Racia
Summary: This study evaluated the pharmacological profile of selected sigma-1 receptor (s(1)R) ligands using a novel object recognition (NOR) test, indicating differences in cognitive functions between s(1)R agonists and antagonists.
PHARMACOLOGICAL REPORTS
(2023)
Article
Chemistry, Multidisciplinary
Vittorio Canale, Michal Kaminski, Wojciech Trybala, Michal Abram, Krzysztof Marciniec, Xavier Bantreil, Frederic Lamaty, Jan Rodriguez Parkitna, Pawel Zajdel
Summary: A solid-state approach was used to synthesize compound PZ-1190, a multitarget ligand for serotonin and dopamine receptors with potential antipsychotic activity. The developed multistep mechanochemical protocol improved the overall yield, reduced the reaction time, and decreased the use of toxic reagents and organic solvents. The described procedures represent rare examples of mechanochemical reduction and aliphatic alcohol oxidation, which could be sustainable methods for obtaining crucial compounds.
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2023)