Sohvi Luukkonen, Helle W van den Maagdenberg, Michael T M Emmerich, Gerard J P van Westen
The factors determining a drug's success are manifold, making de novo drug design an inherently multi-objective optimisation (MOO) problem. With the advent of machine learning and optimisation methods, the field of multi-objective compound design has seen a rapid increase in developments and applications. Population-based metaheuris-tics and deep reinforcement learning are the most commonly used artificial intelligence methods in the field, but recently conditional learning methods are gaining popularity. The former approaches are coupled with a MOO strat-egy which is most commonly an aggregation function, but Pareto-based strategies are widespread too...
April 2023: Current Opinion in Structural Biology
M V Putilina, N V Teplova
Optimization of the choice of neuroprotective therapy regimens in patients with cerebrovascular diseases (CVD), taking into account the synergism of drug interactions, is a basic approach in clinical practice. Unfortunately, modern pharmacology has no unified way of establishing synergistic spectra of drug actions, which would allow systematic investigation of the effects of combinations of drugs. An approach based on studying detailed mechanisms of action suggested combinations of drugs with the greatest possible synergism (by summation and potentiation of effects) for various directions in the treatment of neurological diseases...
2022: Neuroscience and Behavioral Physiology
Ghada A Omran, Eman S H Abd Allah, Sherine Ahmed Mohammed, Doaa M El Shehaby
WIN55, 212-2 mesylate is a synthetic cannabinoid (SC) agonist of CB1 and CB2 receptors with much higher affinity to CB1 receptor than tetrahydrocannabinol and many potential therapeutic effects. Few studies have evaluated SCs effects on more complex animal behavior and sex differences in cannabinoids toxicology. The current study was undertaken for determination of behavioral (Open Field test), biochemical (liver and kidney function test plus GABA & Glutamate levels), histopathological and CB1 immunohistochemistry risks of sub-chronic administration of SC WIN55, 212-2 mesylate in male and female mice...
February 7, 2023: BMC Pharmacology & Toxicology
Leslie Citrome, Sheldon Preskorn
In this month's edition of our evidence-based clinical psychopharmacology journal club, Dr. Leslie Citrome will interview Dr. Sheldon Preskorn, lead author of a pivotal trial assessing the efficacy of sublingual dexmedetomidine for the treatment of acute agitation associated with bipolar disorder. This will be a live event at 11:30 AM EST on the 25th of January 2023, hosted by MedscapeLIVE! and QxMD, with opportunity for questions and interaction. Click the 'Full Text Web' button below to register. Pharmacological strategies to address agitation include a number of intramuscular agents...
January 25, 2023: Psychiatry Update Journal Club: An evidence based psychopharmacology series
Grace Cunliffe, Yi Tang Lim, Woori Chae, Sangyong Jung
Alzheimer's disease (AD) is a neurodegenerative disorder, comprising 70% of dementia diagnoses worldwide and affecting 1 in 9 people over the age of 65. However, the majority of its treatments, which predominantly target the cholinergic system, remain insufficient at reversing pathology and act simply to slow the inevitable progression of the disease. The most recent neurotransmitter-targeting drug for AD was approved in 2003, strongly suggesting that targeting neurotransmitter systems alone is unlikely to be sufficient, and that research into alternate treatment avenues is urgently required...
November 28, 2022: Biomedicines
Dawood Sayed, Jay Grider, Natalie Strand, Jonathan M Hagedorn, Steven Falowski, Christopher M Lam, Vinicius Tieppo Francio, Douglas P Beall, Nestor D Tomycz, Justin R Davanzo, Rohit Aiyer, David W Lee, Hemant Kalia, Soun Sheen, Mark N Malinowski, Michael Verdolin, Shashank Vodapally, Alexios Carayannopoulos, Sameer Jain, Nomen Azeem, Reda Tolba, George C Chang Chien, Priyanka Ghosh, Anthony J Mazzola, Kasra Amirdelfan, Krishnan Chakravarthy, Erika Petersen, Michael E Schatman, Timothy Deer
INTRODUCTION: Painful lumbar spinal disorders represent a leading cause of disability in the US and worldwide. Interventional treatments for lumbar disorders are an effective treatment for the pain and disability from low back pain. Although many established and emerging interventional procedures are currently available, there exists a need for a defined guideline for their appropriateness, effectiveness, and safety. OBJECTIVE: The ASPN Back Guideline was developed to provide clinicians the most comprehensive review of interventional treatments for lower back disorders...
2022: Journal of Pain Research
Beau Kilmer, Bryce Pardo, Toyya A Pujol, Jonathan P Caulkins
BACKGROUND AND AIMS: Synthetic opioids, mostly illegally manufactured fentanyl (IMF), were mentioned in 60% of United States (US) drug overdose deaths in 2020, with dramatic variation across states that mirrors variation in IMF supply. However, little is known about IMF markets in the United States and how they are changing. Researchers have previously used data from undercover cocaine, heroin, and methamphetamine purchases and seizures to examine how their use and related harms respond to changes in price and availability...
October 2022: Addiction
Peng Xu, Haijie Li, Qiyang Qiu, Xiao Xiao, Yi Qiu, Xiangyu Li, Youmei Wang, Wenhua Zhou, Haowei Shen, Wei Cui
N-isopropylbenzylamine, an isomer of methamphetamine, has been used to adulterate methamphetamine, and distributed as fake "Ice" methamphetamine by illicit manufacturers, leading to a world problem of N-isopropylbenzylamine exposure. Though it is unclear whether N-isopropylbenzylamine has addictive potential like methamphetamine, N-isopropylbenzylamine users reported side effects such as headaches and confusion. However, the pharmacological targets and cytotoxicity of this chemical remained unknown. In this study, in vitro toxicity of N-isopropylbenzylamine and its toxicity-related targets were investigated in SN4741, SH-SY5Y or PC12 cell lines that model neurons...
October 2022: Toxicology
Ben Bogun, Megan McKinnel, Matthew Russell, Janine Watson, Erina Mayo, Brooke Marr, Annie Larsen, Jessica Craig
The most common method of domestic methamphetamine manufacture encountered in New Zealand is the hydrogen iodide (HI) reduction of pseudoephedrine/ephedrine. While the overall method used to manufacture methamphetamine has remained consistent, the processes and chemicals utilized have evolved. Understanding the reason for any changes to methamphetamine manufacturing trends can assist jurisdictions with predicting the potential effects of enforcement and legislative initiatives. This paper presents data and trends amassed from suspected clandestine laboratories, associated with the manufacture of methamphetamine, in New Zealand between 2009 and 2021, along with data on methamphetamine, pseudoephedrine, and ephedrine seizures at the border...
January 2023: Journal of Forensic Sciences
Chenglin Li, Kaiji Ni, Meiru Qi, Jie Li, Kexin Yang, Yanli Luo
Mood disorders, such as anxiety and depression, are commonly found in people suffering from chronic pain. Serotonin-norepinephrine reuptake inhibitors (SNRIs) are potential in alleviating chronic pain and are the first-line option for anxiety disorder. The anterior cingulate cortex (ACC) plays a vital role in chronic pain-induced anxiety, but its role in the therapeutic effects of SNRIs remains largely unclear. We used complete Freund's adjuvant (CFA) in this current study to induce chronic inflammatory pain...
2022: Frontiers in Neuroscience
Ping Liao, Qing-Yun Wu, Sen Li, Kai-Bin Hu, Hui-Lin Liu, Hai-Yan Wang, Zai-Yun Long, Xiu-Min Lu, Yong-Tang Wang
Abscisic acid (ABA), a conserved hormone existing in plants and animals, not only regulates blood glucose and inflammation but also has good therapeutic effects on obesity, diabetes, atherosclerosis and inflammatory diseases in animals. Studies have shown that exogenous ABA can pass the blood-brain barrier and inhibit neuroinflammation, promote neurogenesis, enhance synaptic plasticity, improve learning, memory and cognitive ability in the central nervous system. At the same time, ABA plays a crucial role in significant improvement of Alzheimer's disease, depression, and anxiety...
February 15, 2023: Neuropharmacology
Lina Ruan, Kaiyu Guan, Yue Wang, Ming Gu, Yue Chen, Lisha Cai, Ruixuan Ye, Zhengwei Huang, Anqi Guo, Zhengkang Su, Xi Li, Jianchun Pan
Post-traumatic stress disorder (PTSD) is a serious mental disease featured by a stress dysfunction that occurs after an individual has faced intense mental stress, often accompanied by anxiety and chronic pain. Currently, the mainstream drug for PTSD is serotonin reuptake inhibitors (SSRIs), however, their pain management for patients is limited. Baicalein, a Chinese traditional herbal medicine, has shown promising results in treating anxiety, depression, and pain. In this study, we found that baicalein may alleviate single prolonged stress (SPS)-induced PTSD-like behaviors in mice without altering baseline nociceptive sensitivity or activity...
March 2, 2023: Progress in Neuro-psychopharmacology & Biological Psychiatry
Henry Blanton, P Hemachandra Reddy, Khalid Benamar
Chronic pain, one of the most common reasons adults seek medical care, has been linked to restrictions in mobility and daily activities, dependence on opioids, anxiety, depression, sleep deprivation, and reduced quality of life. Alzheimer's disease (AD), a devastating neurodegenerative disorder (characterized by a progressive impairment of cognitive functions) in the elderly, is often co-morbid with chronic pain. AD is one of the most common neurodegenerative disorders in the aged population. The reported prevalence of chronic pain is 45...
February 2023: Experimental Neurology
Shang-Der Chen, Yao-Chung Chuang, Tsu-Kung Lin, Jenq-Lin Yang
Aging is a crucial risk factor for common neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Limited options are available for the treatment of age-related, multiple pathogenic mechanism-contributed diseases that usually advance to irreversible conditions with severe neurological deficits and result in a heavy socioeconomic burden on patients, families, and society. A therapy that decelerates disease progression and reduces the socioeconomic burden stemming from these diseases is required...
January 5, 2023: European Journal of Pharmacology
José Javier Miguel-Hidalgo
Changes induced in the morphology and the multiplicity of functional roles played by astrocytes in brain regions critical to the establishment and maintenance of alcohol abuse suggest that they make an important contribution to the vulnerability to alcohol use disorders. The understanding of the relevant mechanisms accounting for that contribution is complicated by the fact that alcohol itself acts directly on astrocytes altering their metabolism, gene expression, and plasticity, so that the ultimate result is a complex interaction of various cellular pathways, including intracellular calcium regulation, neuroimmune responses, and regulation of neurotransmitter and gliotransmitter release and uptake...
2021: Advances in Neurobiology
Alexei Verkhratsky, Vladimir Parpura, Caterina Scuderi, Baoman Li
Major depressive disorder (MDD) presents multiple clinical phenotypes and has complex underlying pathological mechanisms. Existing theories cannot completely explain the pathophysiological mechanism(s) of MDD, while the pharmacology of current antidepressants is far from being fully understood. Astrocytes, the homeostatic and defensive cells of the central nervous system, contribute to shaping behaviors, and regulating mood and emotions. A detailed introduction on the role of astrocytes in depressive disorders is thus required, to which this chapter is dedicated...
2021: Advances in Neurobiology
John W Bigbee
The central nervous system is the last major organ system in the vertebrate body to yield its cellular structure, due to the complexity of its cells and their interactions. The fundamental unit of the nervous system is the neuron, which forms complex circuits that receive and integrate information and generate adaptive responses. Each neuron is composed of an input domain consisting of multiple dendrites along with the cell body, which is also responsible for the majority of macromolecule synthesis for the cell...
2023: Advances in Neurobiology
Jidong Fang, Patti Miller, Patricia S Grigson
INTRODUCTION: Sleep disturbances are prominent in drug use disorders, including those involving opioids in both humans and animals. Recent studies have shown that administration of liraglutide, a glucagon-like peptide-1 agonist, significantly reduces heroin taking and seeking in rats. In an effort to further understand the action of this substance on physiological functions and to evaluate safety issues for its potential clinical use, the aim of the present study was to determine whether the dose of liraglutide found effective in reducing responding for an opioid also could improve sleep in drug-naïve rats...
November 21, 2022: Brain Research Bulletin
Flaminia Coluzzi, Maria Sole Scerpa, Monica Rocco, Diego Fornasari
Opioids are widely used in cancer and non-cancer pain management. However, many transporters at the blood-brain barrier (BBB), such as P-glycoprotein (P-gp, ABCB1/MDR1), may impair their delivery to the brain, thus leading to opioid tolerance. Nonetheless, opioids may regulate P-gp expression, thus altering the transport of other compounds, namely chemotherapeutic agents, resulting in pharmacoresistance. Other kinds of painkillers (e.g., acetaminophen, dexamethasone) and adjuvant drugs used for neuropathic pain may act as P-gp substrates and modulate its expression, thus making pain management challenging...
November 16, 2022: International Journal of Molecular Sciences
Michael J Li, Steven J Shoptaw
It is estimated that a majority of people who use psychostimulants, particularly methamphetamine (MA) and cocaine, experience withdrawal upon abstinence from sustained use. This review of clinical research reports the evidence regarding biomedical and behavioral treatments for psychostimulant withdrawal symptoms. It provides a framework for clinicians and scientists to increase impact on attenuating MA and cocaine withdrawal during initial and sustained abstinence. Articles reviewed included reports of controlled clinical trials (randomized or non-randomized) reporting at least one withdrawal symptom among the outcomes or specifically studying patients in withdrawal...
April 2023: Addiction
2022-11-21 08:03:25
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