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https://www.readbyqxmd.com/read/29042244/selectivity-of-coronaridine-congeners-at-nicotinic-acetylcholine-receptors-and-inhibitory-activity-on-mouse-medial-habenula
#1
Hugo R Arias, Xiaotao Jin, Dominik Feuerbach, Ryan M Drenan
The inhibitory activity of coronaridine congeners on human (h) α4β2 and α7 nicotinic acetylcholine receptors (AChRs) is determined by Ca(2+) influx assays, whereas their effects on neurons in the ventral inferior (VI) aspect of the mouse medial habenula (MHb) are determined by patch-clamp recordings. The Ca(2+) influx results clearly establish that coronaridine congeners inhibit hα3β4 AChRs with higher selectivity compared to hα4β2 and hα7 subtypes, and with the following potency sequence, for hα4β2: (±)-18-methoxycoronaridine [(±)-18-MC]>(+)-catharanthine>(±)-18-methylaminocoronaridine [(±)-18-MAC] ∼ (±)-18-hydroxycoronaridine [(±)-18-HC]; and for hα7: (+)-catharanthine>(±)-18-MC>(±)-18-HC>(±)-18-MAC...
October 16, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28857330/increased-habenular-connectivity-in-opioid-users-is-associated-with-an-%C3%AE-5-subunit-nicotinic-receptor-genetic-variant
#2
Kaylah Curtis, Humsini Viswanath, Kenia M Velasquez, David L Molfese, Mark J Harding, Eduardo Aramayo, Philip R Baldwin, Elisa Ambrosi, Alok Madan, Michelle Patriquin, B Christopher Frueh, J Christopher Fowler, Thomas R Kosten, David A Nielsen, Ramiro Salas
BACKGROUND AND OBJECTIVES: Opioid use disorder (OUD) is a chronic disorder with relapse based on both desire for reinforcement (craving) and avoidance of withdrawal. The aversive aspect of dependence and relapse has been associated with a small brain structure called the habenula, which expresses large numbers of both opioid and nicotinic receptors. Additionally, opioid withdrawal symptoms can be induced in opioid-treated rodents by blocking not only opioid, but also nicotinic receptors...
August 31, 2017: American Journal on Addictions
https://www.readbyqxmd.com/read/28691660/endoribonuclease-type-ii-toxin-antitoxin-systems-functional-or-selfish
#3
Bhaskar Chandra Mohan Ramisetty, Ramachandran Sarojini Santhosh
Most bacterial genomes have multiple type II toxin-antitoxin systems (TAs) that encode two proteins which are referred to as a toxin and an antitoxin. Toxins inhibit a cellular process, while the interaction of the antitoxin with the toxin attenuates the toxin's activity. Endoribonuclease-encoding TAs cleave RNA in a sequence-dependent fashion, resulting in translational inhibition. To account for their prevalence and retention by bacterial genomes, TAs are credited with clinically significant phenomena, such as bacterial programmed cell death, persistence, biofilms and anti-addiction to plasmids...
July 8, 2017: Microbiology
https://www.readbyqxmd.com/read/28489458/toxicokinetics-of-ibogaine-and-noribogaine-in-a-patient-with-prolonged-multiple-cardiac-arrhythmias-after-ingestion-of-internet-purchased-ibogaine
#4
Marieke Henstra, Liza Wong, Abdel Chahbouni, Noortje Swart, Cor Allaart, Ferdi Sombogaard
BACKGROUND: Ibogaine is an agent that has been evaluated as an unapproved anti-addictive agent for the management of drug dependence. Sudden cardiac death has been described to occur secondary to its use. We describe the clinical effects and toxicokinetics of ibogaine and noribogaine in a single patient. For this purpose, we developed a LC-MS/MS-method to measure ibogaine and noribogaine plasma-concentrations. We used two compartments with first order absorption. CASE DETAILS: The maximum concentration of ibogaine was 1...
July 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28479740/effect-of-shankhpushpi-on-alcohol-addiction-in-mice
#5
Mahi Heba, Sana Faraz, Sugato Banerjee
Alcohol addiction is a worldwide problem. It has mainly two components: dependence and withdrawal. Characteristic properties of most anti-addictive compounds include anti-anxiety, anticonvulsant, antidepressant, and nootropic actions. Shankhpushpi (Convolvulus pluricaulis. Convolvulaceae), known ethnopharmacologically as brain tonic, possess all the properties mentioned above. Here, we screen shankhpushpi for possible anti-addictive potential. Effect of shankhpushpi churna was measured on ethanol withdrawal anxiety using elevated plus maze...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28382542/kk-92a-a-novel-gabab-receptor-positive-allosteric-modulator-attenuates-nicotine-self-administration-and-cue-induced-nicotine-seeking-in-rats
#6
Xia Li, Emmanuel Sturchler, Katarzyna Kaczanowska, Michael Cameron, M G Finn, Patrick Griffin, Patricia McDonald, Athina Markou
RATIONALE: GABAB receptors (GABABR) play a critical role in GABAergic neurotransmission in the brain and are thought to be one of the most promising targets for the treatment of drug addiction. GABABR positive allosteric modulators (PAMs) have shown promise as potential anti-addictive therapies, as they lack the sedative and muscle relaxant properties of full GABAB receptor agonists such as baclofen. OBJECTIVES: The present study was aimed at developing novel, selective, and potent GABABR PAMs with efficacy on abuse-related effects of nicotine...
May 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28339199/structure-based-discovery-of-new-antagonist-and-biased-agonist-chemotypes-for-the-kappa-opioid-receptor
#7
Zhong Zheng, Xi-Ping Huang, Thomas J Mangano, Rodger Zou, Xin Chen, Saheem A Zaidi, Bryan L Roth, Raymond C Stevens, Vsevolod Katritch
The ongoing epidemics of opioid overdose raises an urgent need for effective antiaddiction therapies and addiction-free painkillers. The κ-opioid receptor (KOR) has emerged as a promising target for both indications, raising demand for new chemotypes of KOR antagonists as well as G-protein-biased agonists. We employed the crystal structure of the KOR-JDTic complex and ligand-optimized structural templates to perform virtual screening of available compound libraries for new KOR ligands. The prospective virtual screening campaign yielded a high 32% hit rate, identifying novel fragment-like and lead-like chemotypes of KOR ligands...
April 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28285325/mglu1-receptor-as-a-drug-target-for-treatment-of-substance-use-disorders-time-to-gather-stones-together
#8
REVIEW
Olga A Dravolina, Edwin Zvartau, Wojciech Danysz, Anton Y Bespalov
Modulation of the mGlu1 receptor was repeatedly shown to inhibit various phenomena associated with exposure to abused drugs. Efficacy in preclinical models was observed with both positive and negative allosteric modulators (PAMs and NAMs, respectively) using essentially non-overlapping sets of experimental methods. Taken together, these data indicate that the mGlu1 receptor certainly plays a significant role in the plasticity triggered by the exposure to abused drugs and is involved in the maintenance of drug-seeking and drug-taking behaviors...
May 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28266890/examination-of-the-phenomenology-of-the-ibogaine-treatment-experience-role-of-altered-states-of-consciousness-and-psychedelic-experiences
#9
Annamarie Heink, Steve Katsikas, Tiffany Lange-Altman
Psychedelic drugs have historically been used for ritualistic purposes and to help individuals gain insight. Ibogaine, a naturally occurring psychoactive substance, has been reported to have anti-addictive properties that aid in the treatment of substance use disorders. An online survey obtained retrospective data from individuals who used ibogaine in the past. Individuals who used ibogaine tended to describe thematically similar experiences post-treatment. This study adds to the literature by using the 5d-ASC, a psychometrically sound measure of altered states of consciousness (ASCs), to examine the ASCs induced by ibogaine and discusses the demographic characteristics of those who seek ibogaine treatment (N = 27)...
March 7, 2017: Journal of Psychoactive Drugs
https://www.readbyqxmd.com/read/28190678/a-unique-natural-selective-kappa-opioid-receptor-agonist-salvinorin-a-and-its-roles-in-human-therapeutics
#10
André Cruz, Sara Domingos, Eugenia Gallardo, Ana Martinho
Until the mid-60s, only the Mazatecs, an indigenous group from Oaxaca, Mexico, used Salvia Divinorum (S. divinorum) due to its hallucinogen properties. Later it was found that the hallucinogen effects of this plant were caused by the presence of a neoclerodane diterpene Salvinorin A (salvinorin A), which is a highly selective agonist of kappa-opioid receptor (KOR) that cause more intense hallucinations than the common hallucinogens as lysergic acid, mushrooms, ecstasy and others. In fact, smoking of only 200-500 μg of S...
May 2017: Phytochemistry
https://www.readbyqxmd.com/read/28107617/fabrication-of-nanostructured-mesoporous-germanium-for-application-in-laser-desorption-ionization-mass-spectrometry
#11
Hazem H Abdelmaksoud, Taryn M Guinan, Nicolas H Voelcker
Surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) is a high-throughput analytical technique ideally suited for small-molecule detection from different bodily fluids (e.g., saliva, urine, and blood plasma). Many SALDI-MS substrates require complex fabrication processes and further surface modifications. Furthermore, some substrates show instability upon exposure to ambient conditions and need to be kept under special inert conditions. We have successfully optimized mesoporous germanium (meso-pGe) using bipolar electrochemical etching and efficiently applied meso-pGe as a SALDI-MS substrate for the detection of illicit drugs such as in the context of workplace, roadside, and antiaddictive drug compliance...
February 6, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28007642/suppressing-effect-of-saikosaponin-a-an-active-ingredient-of-bupleurum-falcatum-on-chocolate-self-administration-and-reinstatement-of-chocolate-seeking-in-rats
#12
Irene Lorrai, Paola Maccioni, Mauro A M Carai, Alessandro Capra, M Paola Castelli, Antonella Riva, Paolo Morazzoni, Gian Luigi Gessa, Giancarlo Colombo
Recent lines of experimental evidence have indicated that saikosaponin A (SSA) - a bioactive ingredient of the medicinal plant, Bupleurum falcatum L. - suppressed alcohol, morphine, and cocaine self-administration in rats. The present paper was designed to assess whether the protective properties of SSA on addiction-related behaviors generalize to a hyperpalatable food such as a chocolate-flavored beverage (CFB). To this end, rats were initially trained to lever-respond for CFB [5% (w/v) Nesquik(®) powder in water] under fixed ratio (FR) 10 (FR10) schedule of reinforcement...
December 19, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27812593/a-new-synthesis-and-preliminary-evaluation-of-some-analogues-of-mecamylamine-a-compound-with-anti-addiction-properties
#13
David Mangan, Neasa McNabola, Emily H Clark, Isabel Bermudez, Susan Wonnacott, J Mike Southern
A new synthesis of mecamylamine - a known anti-hypertensive drug with anti-addictive properties is described. The new route allowed access to two novel analogues whose activity at two nicotinic acetylcholine receptor subtypes was assessed.
November 22, 2016: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/27734823/-ibogaine-structure-influence-on-human-body-clinical-relevance
#14
REVIEW
Zygmunt Zdrojewicz, Bartłomiej Kuszczak, Natalia Olszak
Ibogaine is a natural chemical compound, which belongs to the indole alkaloid family. It can be naturally found within the root bark of african plant Tabernanthe iboga. Ibogaine plays a significant role among tribal cultures. Ibogaine, in small amount, causes reduction of hunger, thirst and exhaustion. In bigger amount, however, it can cause intensive visions. Other effects include reduction or complete disappearance of absitnence symptoms visible in people addicted to the nicotine, alcohol, methamphetamine, cocaine or opioids, what has been scientifically proven after the tests on animals and small groups of people...
July 29, 2016: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/27678551/choice-between-delayed-food-and-immediate-oxycodone-in-rats
#15
Maria E Secci, Julie A Factor, Charles W Schindler, Leigh V Panlilio
RATIONALE: The choice to seek immediate drug effects instead of more meaningful but delayed rewards is a defining feature of addiction. OBJECTIVES: To develop a rodent model of this behavior, we allowed rats to choose between immediate intravenous delivery of the prescription opioid oxycodone (50 μg/kg) and delayed delivery of palatable food pellets. RESULTS: Rats preferred food at delays up to 30 s, but they chose oxycodone and food equally at 60-s delay and preferred oxycodone over food at 120-s delay...
December 2016: Psychopharmacology
https://www.readbyqxmd.com/read/27617300/coupling-neurogenetics-gars%C3%A2-and-a-nutrigenomic-based-dopaminergic-agonist-to-treat-reward-deficiency-syndrome-rds-targeting-polymorphic-reward-genes-for-carbohydrate-addiction-algorithms
#16
Kenneth Blum, Thomas Simpatico, Rajendra D Badgaiyan, Zsolt Demetrovics, James Fratantonio, Gozde Agan, Marcelo Febo, Mark S Gold
Earlier work from our laboratory, showing anti-addiction activity of a nutraceutical consisting of amino-acid precursors and enkephalinase inhibition properties and our discovery of the first polymorphic gene (Dopamine D2 Receptor Gene [DRD2]) to associate with severe alcoholism serves as a blue-print for the development of "Personalized Medicine" in addiction. Prior to the later genetic finding, we developed the concept of Brain Reward Cascade, which continues to act as an important component for stratification of addiction risk through neurogenetics...
2015: Journal of Reward Deficiency Syndrome
https://www.readbyqxmd.com/read/27448833/quantification-of-anti-addictive-alkaloids-ibogaine-and-voacangine-in-in-vivo-and-in-vitro-grown-plants-of-two-mexican-tabernaemontana-species
#17
Felix Krengel, Josefina Herrera Santoyo, Teresa de Jesús Olivera Flores, Víctor M Chávez Ávila, Francisco J Pérez Flores, Ricardo Reyes Chilpa
Tabernaemontana alba and Tabernaemontana arborea are Apocynaceae species used in Mexican traditional medicine for which little phytochemical information exists. In this study, preliminary gas chromatography/mass spectrometry analyses of different organs obtained from wild plants of both species identified a total of 10 monoterpenoid indole alkaloids (MIAs) and one simple indole alkaloid, nine of which were reported for the first time in these species. Furthermore, callus cultures were established from T. alba leaf explants and regeneration of whole plants was accomplished via somatic embryogenesis...
December 2016: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/27279696/effect-of-withinia-somnifera-and-shilajit-on-alcohol-addiction-in-mice
#18
Priya Bansal, Sugato Banerjee
BACKGROUND: Alcohol addiction is a social problem leading to both loss of health and economic prosperity among addicted individuals. Common properties of anti-addictive compounds include anti-anxiety, anticonvulsants, anti-depressant, and nootropic actions primarily through modulation of gamma-aminobutyric acid (GABA) and serotonergic systems. OBJECTIVE: Here, we screen ashwagandha and shilajit known ethnopharmacologically as nervine tonic and adaptogenic herbs for possible anti-addictive potential...
May 2016: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/27259232/characterization-and-use-of-hapt1-derived-homologous-tumors-as-a-preclinical-model-to-evaluate-therapeutic-efficacy-of-drugs-against-pancreatic-tumor-desmoplasia
#19
Sujit Suklabaidya, Biswajit Das, Syed Azmal Ali, Sumeet Jain, Sharada Swaminathan, Ashok K Mohanty, Susen K Panda, Pujarini Dash, Subhankar Chakraborty, Surinder K Batra, Shantibhusan Senapati
Desmoplasia in human pancreatic cancer (PC) promotes cancer progression and hinders effective drug delivery. The objectives of this study were to characterize a homologous orthotopic model of PC in Syrian golden hamster and investigate the effect of anti-fibrotic (pirfenidone), antioxidant (N-acetyl cysteine, NAC) and anti-addiction (disulfiram, DSF) drugs on desmoplasia and tumor growth in this model. The HapT1 PC cells when implanted orthotopically into hamsters formed tumors with morphological, cellular and molecular similarities to human PC...
July 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/27230395/effects-of-ayahuasca-and-its-alkaloids-on-drug-dependence-a-systematic-literature-review-of-quantitative-studies-in-animals-and-humans
#20
Amanda A Nunes, Rafael G Dos Santos, Flávia L Osório, Rafael F Sanches, José Alexandre S Crippa, Jaime E C Hallak
Recently, the anti-addictive potential of ayahuasca, a dimethyltryptamine(DMT)- and β-carboline-rich hallucinogenic beverage traditionally used by indigenous groups of the Northwest Amazon and currently by syncretic churches worldwide, has received increased attention. To better evaluate this topic, we performed a systematic literature review using the PubMed database to find quantitative studies (using statistical analysis) that assessed the effects of ayahuasca or its components in drug-related symptoms or disorders...
July 2016: Journal of Psychoactive Drugs
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