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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
#1
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...
April 5, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28339199/structure-based-discovery-of-new-antagonist-and-biased-agonist-chemotypes-for-the-kappa-opioid-receptor
#2
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
#3
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...
March 11, 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
#4
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
#5
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
#6
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
#7
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
#8
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 4, 2016: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/27734823/-ibogaine-structure-influence-on-human-body-clinical-relevance
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/27223864/reactivity-to-addictive-drugs-in-the-methylazoxymethanol-mam-model-of-schizophrenia-in-male-and-female-rats
#16
Jana Ruda-Kucerova, Zuzana Babinska, Petra Amchova, Tibor Stark, Filippo Drago, Alexandra Sulcova, Vincenzo Micale
OBJECTIVES: Patients with schizophrenia often suffer comorbid substance abuse regardless of gender. However, the vast majority of studies are only conducted in male subjects. Therefore, the aim of these experiments is to assess addictive behaviors of both sexes in a neurodevelopmental model of schizophrenia induced by prenatal methylazoxymethanol (MAM) acetate exposure. METHODS: MAM (22 mg/kg) was administered intraperitoneally on gestational day 17. Two studies were performed in the offspring: (1) an alcohol-drinking procedure to assess daily intake of 20% alcohol and relapse-like behavior after a period of forced abstinence; (2) Methamphetamine (METH) intravenous self administration (IVSA) followed by forced abstinence and reinstatement phases...
June 21, 2016: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/27137199/the-effects-of-intranasal-oxytocin-in-opioid-dependent-individuals-and-healthy-control-subjects-a-pilot-study
#17
Josh D Woolley, Peter A Arcuni, Christopher S Stauffer, Daniel Fulford, Dean S Carson, Steve Batki, Sophia Vinogradov
RATIONALE: There has been an explosion of research on the potential benefits of the social neuropeptide oxytocin for a number of mental disorders including substance use disorders. Recent evidence suggests that intranasal oxytocin has both direct anti-addiction effects and pro-social effects that may facilitate engagement in psychosocial treatment for substance use disorders. OBJECTIVES: We aimed to assess the tolerability of intranasal oxytocin and its effects on heroin craving, implicit association with heroin and social perceptual ability in opioid-dependent patients receiving opioid replacement therapy (ORT) and healthy control participants...
July 2016: Psychopharmacology
https://www.readbyqxmd.com/read/27020671/anti-addiction-drug-ibogaine-prolongs-the-action-potential-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#18
Lena Rubi, Daniel Eckert, Stefan Boehm, Karlheinz Hilber, Xaver Koenig
Ibogaine is a plant alkaloid used as anti-addiction drug in dozens of alternative medicine clinics worldwide. Recently, alarming reports of life-threatening cardiac arrhythmias and cases of sudden death associated with the ingestion of ibogaine have accumulated. Using whole-cell patch clamp recordings, we assessed the effects of ibogaine and its main metabolite noribogaine on action potentials in human ventricular-like cardiomyocytes derived from induced pluripotent stem cells. Therapeutic concentrations of ibogaine and its long-lived active metabolite noribogaine significantly retarded action potential repolarization in human cardiomyocytes...
April 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/26807959/how-toxic-is-ibogaine
#19
REVIEW
Ruud P W Litjens, Tibor M Brunt
CONTEXT: Ibogaine is a psychoactive indole alkaloid found in the African rainforest shrub Tabernanthe Iboga. It is unlicensed but used in the treatment of drug and alcohol addiction. However, reports of ibogaine's toxicity are cause for concern. OBJECTIVES: To review ibogaine's pharmacokinetics and pharmacodynamics, mechanisms of action and reported toxicity. METHODS: A search of the literature available on PubMed was done, using the keywords "ibogaine" and "noribogaine"...
2016: Clinical Toxicology
https://www.readbyqxmd.com/read/26518330/differential-roles-of-gabab1-subunit-isoforms-on-locomotor-responses-to-acute-and-repeated-administration-of-cocaine
#20
Laura H Jacobson, Fabian F Sweeney, Klemens Kaupmann, Olivia F O'Leary, Martin Gassmann, Bernhard Bettler, John F Cryan
GABAB receptors are crucial modulators of the behavioural effects of drug abuse, and agonists and positive allosteric modulators show promise as pharmacological strategies for anti-addiction therapeutics. GABAB receptors are functional heterodimers of GABAB1 and GABAB2 subunits. The predominant neuronal GABAB1 subunit isoforms are GABAB1a and GABAB1b. Selective ablation of these isoforms in mice revealed differential behavioural responses in fear, cognition and stress sensitivity. However, the influence of the two GABAB1 isoforms on responses to drugs of abuse is unclear...
February 1, 2016: Behavioural Brain Research
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