Article
Biology
Aravinda Babu, Mathew John, M. J. Liji, E. Maria, S. J. Bhaskar, B. K. Binukmar, Ayyiliath M. Sajith, Eeda Koti Reddy, K. V. Dileep, K. Sunil
Summary: Human acetylcholinesterase (hAChE) plays a potential role in acetylcholine management and AChE inhibitors have a significant impact in therapeutics. This study explored the active site geometry of hAChE upon binding to different ligands and discovered two prominent sub-pockets near the active site. Structural bioinformatics analysis identified 132 putative sub-pockets focused tacrine derivatives (SPFTDs) that showed stronger binding affinity than tacrine. The identification of these sub-pockets and SPFTDs provides new possibilities for future drug discovery targeting AChE in the treatment of Alzheimer's disease (AD).
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Asha Hiremathad, Silvia Chaves, Rangappa S. Keri
Summary: Alzheimer's disease is a severe chronic condition with no cure, and current treatments are only temporary. Two different series of molecules have been developed to target the multifactorial nature of the disease, showing potential as drug lead molecules for AD treatment.
CHEMISTRY & BIODIVERSITY
(2021)
Article
Biochemistry & Molecular Biology
Mehrdad Sadafi Kohnehshahri, Gholamabbas Chehardoli, Masoomeh Bahiraei, Tahmineh Akbarzadeh, Akram Ranjbar, Arezoo Rastegari, Zahra Najafi
Summary: The newly designed quinolotacrine hybrids showed promising inhibitory effects on AChE, with one compound exhibiting the best inhibitory activity. Additionally, these compounds demonstrated significant neuroprotective effects in in vitro experiments.
MOLECULAR DIVERSITY
(2022)
Article
Biochemistry & Molecular Biology
Eugenie Nepovimova, Lucie Svobodova, Rafael Dolezal, Vendula Hepnarova, Lucie Junova, Daniel Jun, Jan Korabecny, Tomas Kucera, Zuzana Gazova, Katarina Motykova, Jana Kubackova, Zuzana Bednarikova, Jana Janockova, Catarina Jesus, Luisa Cortes, Joao Pina, Danijela Rostohar, Carlos Serpa, Ondrej Soukup, Laura Aitken, Rebecca E. Hughes, Kamil Musilek, Lubica Muckova, Petr Jost, Marketa Chvojkova, Karel Vales, Martin Valis, Zofia Chrienova, Katarina Chalupova, Kamil Kuca
Summary: The series of tacrine-benzothiazole hybrids show promising anti-AChE properties and capability to block Aβ aggregation, with the most potent derivative being 10w that exhibits highly selective inhibition of AChE. Moreover, 10w also demonstrates strong inhibitory effects against ABAD activity.
BIOORGANIC CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Anna Bubley, Alexaner Erofeev, Peter Gorelkin, Elena Beloglazkina, Alexander Majouga, Olga Krasnovskaya
Summary: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by Aβ aggregation, tau hyperphosphorylation, and loss of cholinergic neurons. AD is also associated with oxidative stress, metal dyshomeostasis, inflammation, and cell cycle dysregulation. In this review, THA-based hybrids are summarized as potential anti-AD agents, highlighting strategies for drug design that have led to cognitive improvements and reduced hepatotoxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jose L. Borioni, Valeria Cavallaro, Ana P. Murray, Alicia B. Penenory, Marcelo Puiatti, Manuela E. Garcia
Summary: Alzheimer's disease is the most alarming neurodegenerative disorder globally, with cholinesterase inhibitors commonly used in clinical treatments. The strategy of synthesizing hybrid cholinesterase inhibitors has shown improved inhibitory activity and enhanced interactions at multiple sites in the enzyme cavity. This approach should be further explored and exploited in this field.
BIOORGANIC CHEMISTRY
(2021)
Article
Plant Sciences
Mingjuan Yang, Xinyu Zhang, Ou Qiao, Haixia Ji, Yi Zhang, Xiaoying Han, Wenzhe Wang, Xia Li, Juan Wang, Lanping Guo, Luqi Huang, Wenyuan Gao
Summary: This study found that rosmarinic acid can reduce the hepatotoxicity of tacrine and both of them can work together to inhibit the progression of Alzheimer's disease. Both in vivo and in vitro experiments showed that rosmarinic acid can alleviate the liver injury induced by tacrine.
Review
Biochemistry & Molecular Biology
Milos Mitic, Tamara Lazarevic-Pasti
Summary: This article discusses the potential link between acetylcholinesterase inhibitors used for Alzheimer's disease and symptoms of clinical depression. While there are indications of a connection, it is not yet proven and other factors besides acetylcholine levels play a role in these complex diseases.
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2021)
Article
Chemistry, Medicinal
Michele Rossi, Michela Freschi, Luciana de Camargo Nascente, Alessandra Salerno, Sarah de Melo Viana Teixeira, Florian Nachon, Fabien Chantegreil, Ondrej Soukup, Lukas Prchal, Marco Malaguti, Christian Bergamini, Manuela Bartolini, Cristina Angeloni, Silvana Hrelia, Luiz Antonio Soares Romeiro, Maria Laura Bolognesi
Summary: Alzheimer's disease's multifactorial nature hinders effective drug development. A research team developed sustainable multi-target-directed ligands based on inexpensive cashew nutshell liquid, selecting compounds through cell toxicity and enzymatic studies to confirm their activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Lin-Xi Wan, Yong-Qi Zhen, Zhen-Xiang He, Yang Zhang, Lan Zhang, Xiaohuan Li, Feng Gao, Xian-Li Zhou
Summary: A new series of N-aryltacrine derivatives were synthesized as potential Alzheimer's disease therapeutics, demonstrating potent cholinesterase inhibitory activity and potential for treating neurodegenerative diseases.
Review
Biochemistry & Molecular Biology
Lucja Justyna Walczak-Nowicka, Mariola Herbet
Summary: Acetylcholinesterase (AChE) plays a crucial role in the pathogenesis of neurodegenerative diseases, with ongoing research focusing on identifying new AChE inhibitors to potentially treat these diseases. The review highlights the importance of AChE inhibitors and their potential use in developing therapies for neurodegenerative diseases. Further investigations into designing and discovering new drugs targeting AChE may lead to effective treatments for neurodegenerative diseases in the future.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Ce Zhang, Mingan Li, Wei Xie, Min Li, Chunna You, Tian Wang, Fenghua Fu
Summary: This study aimed to investigate the myocardial damage in an isoprenaline (ISO)-induced MI mice model during Huperzine A microspheres (HAM) treatment. The results showed that continuous acetylcholinesterase (AChE) inhibition could protect the heart from ischemic damage and HAM exhibited anti-inflammatory effects through regulating the α7nAChR-dependent JAK2/STAT3 signaling pathway.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Neurosciences
Michelle R. Doyle, Agnieszka Sulima, Kenner C. Rice, Gregory T. Collins
Summary: A subset of female rats showed high levels of MDPV self-administration, which was influenced by their reinforcement history with cocaine or food. Individual differences in MDPV intake were observed under different reinforcement schedules, indicating the potential impact of individual variability on drug-taking behavior.
PSYCHOPHARMACOLOGY
(2021)
Article
Behavioral Sciences
Sean D. Regnier, William W. Stoops, Joshua A. Lile, Joseph L. Alcorn III, B. Levi Bolin, Anna R. Reynolds, Lon R. Hays, Abner O. Rayapati, Craig R. Rush
Summary: Despite decades of research, the FDA has not approved any pharmacotherapy for cocaine use disorder. This study investigated the use of naltrexone-bupropion combinations as a potential treatment option. The results showed that these combinations did not significantly decrease cocaine self-administration and did not provide support for their use in treating cocaine use disorder. Future research should explore novel drug combinations to reduce cocaine self-administration.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2023)
Article
Biochemistry & Molecular Biology
Tereza Cristina Santos Evangelista, Oscar Lopez, Sabrina Baptista Ferreira, Jose G. Fernandez-Bolanos, Magne O. Sydnes, Emil Lindback
Summary: The synthesis of four tetra-tacrine clusters with varying linker lengths attached to a central scaffold was investigated for their multivalent inhibition potencies against acetylcholinesterase. Two of the clusters demonstrated significant binding affinity increases of up to 3.2 times when connected to the central scaffold.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Kenneth Grasing, Yungao Yang, Shuangteng He
PHARMACOLOGICAL RESEARCH
(2015)
Review
Behavioral Sciences
Kenneth Grasing
BEHAVIOURAL BRAIN RESEARCH
(2016)
Article
Clinical Neurology
Christopher D. Verrico, Colin N. Haile, Richard De la Garza, Kenneth Grasing, Thomas R. Kosten, Thomas F. Newton
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2016)
Article
Neurosciences
Haiyang Xu, Sasmita Das, Marc Sturgill, Colin Hodgkinson, Qiaoping Yuan, David Goldman, Kenneth Grasing
PSYCHOPHARMACOLOGY
(2017)
Article
Cardiac & Cardiovascular Systems
Kamal Gupta, Rishi Sharma, Vikas Singh, Reza Masoomi, Kottarappat N. Dileepan, Jianghua He, Donald D. Smith, Buddhadeb Dawn, Kenneth Grasing
CARDIOVASCULAR TOXICOLOGY
(2018)
Article
Behavioral Sciences
Kenneth Grasing, Yungao Yang, Shuangteng He
BEHAVIOURAL PHARMACOLOGY
(2011)
Article
Substance Abuse
Kenneth Grasing, Deepan Mathur, Thomas F. Newton, Cherilyn DeSouza
DRUG AND ALCOHOL DEPENDENCE
(2010)
Article
Biochemistry & Molecular Biology
Shaowu Cheng, Longxuan Li, Shuangteng He, Jun Liu, Yuning Sun, Minchao He, Kenneth Grasing, Richard T. Premont, William Z. Suo
JOURNAL OF BIOLOGICAL CHEMISTRY
(2010)
Article
Psychiatry
Thomas F. Newton, Richard De La Garza, Ken Grasing
PSYCHIATRY RESEARCH
(2010)
Article
Psychiatry
Kenneth Grasing, Deepan Mathur, Thomas F. Newton, Cherilyn DeSouza
PSYCHIATRY RESEARCH
(2013)
Article
Substance Abuse
Kenneth Grasing, Deepan Mathur, Cherilyn Desouza
SUBSTANCE USE & MISUSE
(2010)
Article
Clinical Neurology
Xiang-Ping Chu, Kenneth A. Grasing, John Q. Wang
TRANSLATIONAL STROKE RESEARCH
(2014)
Article
Substance Abuse
Kenneth Grasing, Deepan Mathur, Cherilyn DeSouza, Thomas F. Newton, David E. Moody, Marc Sturgill
AMERICAN JOURNAL ON ADDICTIONS
(2016)
Letter
Substance Abuse
Aashish S. Morani, Vikram Panwar, Kenneth Grasing
AMERICAN JOURNAL ON ADDICTIONS
(2013)
Article
Behavioral Sciences
Amine Bahi
Summary: Gestational environmental enrichment (EE) has protective effects on social stress-induced anxiety-like behaviors and excessive ethanol consumption through increasing BDNF levels.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2024)
Article
Behavioral Sciences
Sarabesh Natarajan, Grant Abass, Lucas Kim, Corinne Wells, Amir H. Rezvani, Edward D. Levin
Summary: Multiple neural systems, including dopamine D1 receptors and glutamate NMDA receptors, are involved in nicotine reinforcement. Acute blockade of D1 receptors decreases nicotine self-administration, while acute blockade of NMDA receptors increases it. Chronic blockade of NMDA receptors decreases nicotine self-administration. Memantine attenuates the decrease in nicotine self-administration caused by chronic D1 antagonist SCH-23390.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2024)
Article
Behavioral Sciences
David R. Maguire
Summary: The study found that Lorcaserin alone reduces ventilation and enhances the ventilatory-depressant effects of opioids. This suggests that combining a 5-HT2C receptor agonist with opioids may increase the risk of ventilatory depression without reducing abuse.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2024)
Article
Behavioral Sciences
Fen Liu, Qing Tian, Hui-Ling Tang, Xiang Cheng, Wei Zou, Ping Zhang
Summary: This study demonstrates the attenuating effect of H2S on PD-associated depression by improving hippocampal synaptic plasticity.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2024)
Article
Behavioral Sciences
Mehrsa Rahimi-Danesh, Mohammad-Ali Samizadeh, Amir-Ehsan Sajadi, Tara Rezvankhah, Salar Vaseghi
Summary: This study investigated the effects of lithium on freezing behavior and pain perception in a fear-conditioning model in rats. The results showed that lithium had no effect on freezing behavior and pain subthreshold in all rats. Extinction training decreased freezing behavior, with more efficacy in females. Gender differences were also observed in the effects of extinction training.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2024)