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Ketamine drug dependence

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https://www.readbyqxmd.com/read/29191019/affinity-of-ketamine-to-clinically-relevant-transporters
#1
Markus Keiser, Mahmoud Hasan, Stefan Oswald
Ketamine is a widely used intravenous anaesthetic drug that has also a pronounced analgesic effect. Moreover, one of its metabolites was very recently shown to possess antidepressant activity. Consequently, oral administration of ketamine may become of interest in the future. There is evidence from in vitro data, drug-drug interactions and from the physicochemical properties of the drug that ketamine may be a substrate of drug transporters. Thus, it was the aim of this study to investigate the affinity of ketamine to clinically relevant transporter proteins that are expected to affect its intestinal absorption, distribution and excretion...
November 30, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29167877/utility-of-imaging-based-biomarkers-for-glutamate-targeted-drug-development-in-psychotic-disorders-a-randomized-clinical-trial
#2
Daniel C Javitt, Cameron S Carter, John H Krystal, Joshua T Kantrowitz, Ragy R Girgis, Lawrence S Kegeles, John D Ragland, Richard J Maddock, Tyler A Lesh, Costin Tanase, Philip R Corlett, Douglas L Rothman, Graeme Mason, Maolin Qiu, James Robinson, William Z Potter, Marlene Carlson, Melanie M Wall, Tse-Hwei Choo, Jack Grinband, Jeffrey A Lieberman
Importance: Despite strong theoretical rationale and preclinical evidence, several glutamate-targeted treatments for schizophrenia have failed in recent pivotal trials, prompting questions as to target validity, compound inadequacy, or lack of target engagement. A key limitation for glutamate-based treatment development is the lack of functional target-engagement biomarkers for translation between preclinical and early-stage clinical studies. We evaluated the utility of 3 potential biomarkers-ketamine-evoked changes in the functional magnetic imaging (fMRI) blood oxygen level-dependent response (pharmacoBOLD), glutamate proton magnetic resonance spectroscopy (1H MRS), and task-based fMRI-for detecting ketamine-related alterations in brain glutamate...
November 22, 2017: JAMA Psychiatry
https://www.readbyqxmd.com/read/29146197/illicit-drug-ketamine-induces-adverse-effects-from-behavioral-alterations-and-oxidative-stress-to-p53-regulated-apoptosis-in-medaka-fish-under-environmentally-relevant-exposures
#3
Pei-Han Liao, Wen-Kai Yang, Ching-Hsin Yang, Chun-Hon Lin, Chin-Chu Hwang, Pei-Jen Chen
With increasing problems of drug abuse worldwide, aquatic ecosystems are contaminated by human pharmaceuticals from the discharge of hospital or municipal effluent. However, ecotoxicity data and related toxic mechanism for neuroactive controlled or illicit drugs are still lacking, so assessing the associated hazardous risk is difficult. This study aims to investigate the behavioral changes, oxidative stress, gene expression and neurotoxic or apoptosis effect(s) in larvae of medaka fish (Oryzias latipes) with environmentally relevant exposures of ketamine (KET) solutions for 1-14 days...
November 13, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29135596/general-anesthetics-to-treat-major-depressive-disorder-clinical-relevance-and-underlying-mechanisms
#4
Laszlo Vutskits
Major depressive disorder is a frequent and devastating psychological condition with tremendous public health impact. The underlying pathophysiological mechanisms involve abnormal neurotransmission and a relatedly impaired synaptic plasticity. Since general anesthetics are potent modulators of neuronal activity and, thereby, can exert long-term context-dependent impact on neural networks, an intriguing hypothesis is that these drugs could enhance impaired neural plasticity associated with certain psychiatric diseases...
November 10, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/29111148/effects-of-opioid-and-nonopioid-analgesics-on-canine-wheal-formation-and-cultured-human-mast-cell-degranulation
#5
Eric Schmidt-Rondon, Zhenping Wang, Shelle A Malkmus, Anna Di Nardo, Keith Hildebrand, Linda Page, Tony L Yaksh
Mast cell (MC) degranulation has been implicated in the side effect profile of a variety of clinically useful agents. Thus, after intrathecal delivery, formation of space-occupying, meningeally-derived masses may be related to local MC degranulation. We systematically characterized degranulating effects of opioid and nonopioid analgesics on cutaneous flares in the dog and in primary human MC (hMC) cultures. METHODS: Dogs were anesthetized with IV propofol and received intradermal (ID) injections (50μL)...
October 27, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29096588/non-nmda-receptor-mediated-vibrotactile-responses-of-neurons-from-the-hindpaw-representation-in-the-rat-si-cortex
#6
Bige Vardar, Burak Güçlü
Non-NMDA receptor-mediated vibrotactile responses of neurons from the hindpaw representation were investigated in the rat SI cortex. We recorded single-unit spikes evoked by sinusoidal (duration: 500 ms; frequency: 5, 40, and 250 Hz; amplitude: 100 μm peak-to-peak) stimulation of the glabrous skin. The responses were obtained with microinjection of aCSF (sham), bicuculline, and AMPA near the isolated neurons in anaesthetized rats. Blocking most of the NMDA receptors by ketamine revealed local dynamics differentially modulated by each drug...
September 2017: Somatosensory & Motor Research
https://www.readbyqxmd.com/read/29055748/sex-and-dose-dependent-abuse-liability-of-repeated-subanesthetic-ketamine-in-rats
#7
Kristin J Schoepfer, Caroline E Strong, Samantha K Saland, Katherine N Wright, Mohamed Kabbaj
RATIONALE: Subanesthetic ketamine (KET) elicits rapid, robust, but transient antidepressant effects. KET's antidepressant actions can be augmented and maintained for a longer duration when repeatedly delivered. However, KET is recreationally abused, raising long-term treatment safety concerns. Women are more likely than men to seek treatment for depression, escalate from casual to compulsive drug use, and are more sensitive to antidepressants. Similarly, female rodents are more sensitive than males to KET's rapid antidepressant-like behavioral effects; dose-response thresholds in these assays equal 2...
October 18, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/29020410/the-requirement-of-l-type-voltage-dependent-calcium-channel-l-vdcc-in-the-rapid-acting-antidepressant-like-effects-of-scopolamine-in-mice
#8
Hanjie Yu, Mengmeng Li, Xinbei Shen, Dan Lv, Xin Sun, Jinting Wang, Xinmei Gu, Jingning Hu, Chuang Wang
Background: Previous studies have shown that a low dose of scopolamine produces rapid-acting antidepressant-like actions in rodents. Understanding the mechanisms underlying this effect and the dose-dependent variations of drug responses remains an important task. L-type voltage-dependent calcium channels (L-VDCC) were found to mediate rapid-acting antidepressant effects of certain medications (e.g., ketamine). Therefore, it is of great interest to determine the involvement of L-VDCC in the action of scopolamine...
August 25, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28988615/mechanism-of-synergistic-action-on-behavior-oxidative-stress-and-inflammation-following-co-treatment-with-ketamine-and-different-antidepressant-classes
#9
Gislaine Z Réus, Beatriz I Matias, Amanda L Maciel, Helena M Abelaira, Zuleide M Ignácio, Airam B de Moura, Danyela Matos, Lucineia G Danielski, Fabricia Petronilho, André F Carvalho, João Quevedo
BACKGROUND: Major depressive disorder (MDD) affects many people in the world. However, around 40% of patients do not respond to any pharmacological drugs. An alternative is to use a combination of different pharmacological groups or the combination of a classical antidepressant with a substance that can potentiate its effect. Thus, this study aimed to investigate the synergistic interactions between different antidepressants, including fluoxetine, quetiapine and lamotrigine in combination with ketamine, a N-methyl-d-aspartate (NMDA) receptor antagonist...
May 6, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28958905/-uro-and-nephrotoxic-effects-of-drugs-of-abuse-literature-review-and-pharmaco-epidemiological-survey-in-france-and-in-the-marseille-area
#10
Marion Gully, Élisabeth Frauger, Michel Spadari, Liselotte Pochard, Vanessa Pauly, Fanny Romain, Bertrand Gondouin, Marion Sallée, Julie Moussi-Frances, Stéphane Burtey, Bertrand Dussol, Laurent Daniel, Joëlle Micallef, Noémie Jourde-Chiche
A great diversification of drugs of abuse has been observed in recent years, both in the populations using them and in the types of drugs. Although dependency and psychiatric disorders associated with the abuse of these substances is well known, somatic complications, uro-nephrotoxicity in particular, are less recognized. We propose here an overview of the products used by drugs abusers in France, through the analysis of the national pharmaco-epidemiological study Observation des produits psychotropes illicites ou détournés de leur utilisation médicamenteuse (OPPIDUM)...
September 25, 2017: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/28954811/preclinical-characterization-of-r-3-3s-4s-3-fluoro-4-4-hydroxyphenyl-piperidin-1-yl-1-4-methylbenzyl-pyrrolidin-2-one-bms-986169-a-novel-intravenous-glutamate-n-methyl-d-aspartate-2b-glun2b-receptor-negative-allosteric-modulator-with-potential-in-major-depressive
#11
Linda J Bristow, Jyoti Gulia, Michael R Weed, Bettadapura N Srikumar, Yu-Wen Li, John D Graef, Pattipati S Naidu, Charulatha Sanmathi, Jayant Aher, Tanmaya Bastia, Mahesh Paschapur, Narasimharaju Kalidindi, Kuchibholta Vijaya Kumar, Thaddeus Molski, Rick Pieschl, Alda Fernandes, Jeffrey M Brown, Digavalli V Sivarao, Kimberly Newberry, Mark Bookbinder, Joseph Polino, Deborah Keavy, Amy Newton, Eric Shields, Jean Simmermacher, James Kempson, Jianqing Li, Huiping Zhang, Arvind Mathur, Raja Reddy Kallem, Meenakshee Sinha, Manjunath Ramarao, Reeba K Vikramadithyan, Srinivasan Thangathirupathy, Jayakumar Warrier, Joanne J Bronson, Richard E Olson, John E Macor, Charlie F Albright, Dalton King, Lorin A Thompson, Lawrence R Marcin, Michael Sinz
(R)-3-((3S,4S)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one (BMS-986169), and the phosphate prodrug (BMS-986163), were identified from a drug discovery effort focused on the development of novel, intravenous, glutamate N-methyl-D-aspartate 2B receptor (GluN2B) negative allosteric modulators for treatment resistant depression (TRD). BMS-986169 showed high binding affinity for the GluN2B subunit allosteric modulatory site (Ki = 4.03-6.3 nM) and selectively inhibited GluN2B receptor function in Xenopus oocytes expressing human N-methyl-D-aspartate receptor subtypes (IC50 = 24...
September 27, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28947331/ketamine-and-aminoguanidine-differentially-affect-bdnf-and-mtor-gene-expression-in-the-prefrontal-cortex-of-adult-male-rats
#12
Vitor Silva Pereira, Betina Elfving, Sâmia R L Joca, Gregers Wegener
The rapid and sustained antidepressant properties of ketamine provide evidence of the importance of the glutamatergic system in the neurobiology of depression. The antidepressant-like effects of ketamine are dependent on brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR) in limbic brain areas. The nitrergic system is closely related to the glutamatergic system and generates antidepressant-like effects when blocked. The aim of this study was to investigate whether the behavioural effects induced by the inhibition of nitric oxide (NO) synthesis by aminoguanidine or N-methyl-D-aspartate (NMDA) receptor blockade by ketamine would affect the gene expression of Bdnf and Mtor in the ventromedial prefrontal cortex in rats...
November 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28939975/ketamine-induced-glutamatergic-mechanisms-of-sleep-and-wakefulness-insights-for-developing-novel-treatments-for-disturbed-sleep-and-mood
#13
Wallace C Duncan, Elizabeth D Ballard, Carlos A Zarate
Ketamine, a drug with rapid antidepressant effects and well-described effects on slow wave sleep (SWS), is a useful intervention for investigating sleep-wake mechanisms involved in novel therapeutics. The drug rapidly (within minutes to hours) reduces depressive symptoms in individuals with major depressive disorder (MDD) or bipolar disorder (BD), including those with treatment-resistant depression. Ketamine treatment elevates extracellular glutamate in the prefrontal cortex. Glutamate, in turn, plays a critical role as a proximal element in a ketamine-initiated molecular cascade that increases synaptic strength and plasticity, which ultimately results in rapidly improved mood...
September 23, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28934076/delayed-urinary-symptoms-induced-by-ketamine
#14
María Robles-Martínez, Alfonso C Abad, Violeta Pérez-Rodríguez, Elena Ros-Cucurull, Abderraman Esojo, Carlos Roncero
One of the side-effects of ketamine abuse is genito-urinary damage. This report describes a case of a former ketamine user who presented with urinary symptoms associated with ketamine years after stopping consumption. This was a 26-year-old male with a history of ketamine abuse. He started treatment for alcohol dependence at age 19. He smoked marijuana daily and denied any other drug use. During the follow-up, urinary symptoms were evidenced (dysuria, frequency, urgency, incontinence, nocturia, hematuria, and suprapubic pain)...
September 21, 2017: Journal of Psychoactive Drugs
https://www.readbyqxmd.com/read/28877967/memantine-and-ketamine-differentially-alter-nmda-receptor-desensitization
#15
Nathan G Glasgow, Nadezhda V Povysheva, Andrea M Azofeifa, Jon W Johnson
Memantine and ketamine are clinically useful NMDA receptor (NMDAR) open channel blockers that inhibit NMDARs with similar potency and kinetics, but display vastly different clinical profiles. This discrepancy has been hypothesized to result from inhibition by memantine and ketamine of overlapping but distinct NMDAR subpopulations. For example, memantine but not ketamine may inhibit extrasynaptic NMDARs more effectively than synaptic NMDARs. However, the basis for preferential NMDAR inhibition depending on subcellular location has not been investigated systematically...
October 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28868303/adjuvants-to-local-anesthetics-current-understanding-and-future-trends
#16
EDITORIAL
Amlan Swain, Deb Sanjay Nag, Seelora Sahu, Devi Prasad Samaddar
Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by its duration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action...
August 16, 2017: World Journal of Clinical Cases
https://www.readbyqxmd.com/read/28814306/blood-acid-base-status-in-impala-aepyceros-melampus-immobilised-and-maintained-under-total-intravenous-anaesthesia-using-two-different-drug-protocols
#17
Gareth E Zeiler, Leith C R Meyer
BACKGROUND: In mammals, homeostasis and survival are dependent on effective trans-membrane movement of ions and enzyme function, which are labile to extreme acid-base changes, but operate efficiently within a narrow regulated pH range. Research in patients demonstrating a pH shifts outside the narrow regulated range decreased the cardiac output and systemic vascular resistance and altered the oxygen binding to haemoglobin. These cardiopulmonary observations may be applicable to the risks associated with anaesthesia and performance of wildlife ungulates on game farms...
August 16, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28807162/chinese-herbal-medicine-for-the-treatment-of-drug-addiction
#18
Weili Zhu, Yinan Zhang, Yingjie Huang, Lin Lu
This chapter summarizes recent developments in preclinical and clinical research on Chinese herbal medicines and their neurochemical mechanism of action for the treatment of drug addiction. We searched Chinese and English scientific literature and selected several kinds of Chinese herbal medicines that have beneficial effects on drug addiction. Ginseng (Renshen) may be clinically useful for the prevention of opioid abuse and dependence. Rhizoma Corydalis (Yanhusuo) may be used to prevent relapse to chronic drug dependence...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28760591/the-hairy-lizard-heterothermia-affects-anaesthetic-requirements-in-the-arabian-oryx-oryx-leucoryx
#19
Mads F Bertelsen, Osama Mohammed, Tobias Wang, Paul R Manger, David Michael Scantlebury, Khairi Ismael, Nigel C Bennett, Abdulaziz Alagaili
OBJECTIVE: To study the effect of heterothermia on anaesthetic drug requirements in semi-free ranging Arabian oryx and to assess the temperature quotient (Q10) of oxygen consumption. STUDY DESIGN: Prospective observational study and controlled metabolic experiment. ANIMALS: Sixty-eight anaesthetic events in 59 Arabian oryx from Mahazat As-Sayd protected area, Saudi Arabia METHODS: Anaesthesia was induced by remote injection of 25 mg ketamine, 10 mg midazolam and 0...
March 6, 2017: Veterinary Anaesthesia and Analgesia
https://www.readbyqxmd.com/read/28737446/quantitative-in-vitro-phenotyping-and-prediction-of-drug-interaction-potential-of-cyp2b6-substrates-as-victims
#20
Raghava Choudary Palacharla, Ramakrishna Nirogi, Venkatesham Uthukam, Arunkumar Manoharan, Ranjith Kumar Ponnamaneni, Ilayaraja Kalaikadhiban
1. Determination of fm, CYP for a compound is critical to assess the potential risk of a drug candidate as a victim of DDI. Several compounds are identified as CYP2B6 substrates but the fm, CYP2B6 values are not determined quantitatively 2. Two methods of reaction phenotyping, the chemical inhibition method, and metabolism in rCYP enzymes, were used to determine the relative contributions of the enzymes. Chemical inhibition method was also conducted in the presence of BSA (0.5% w/v) 3. The results confirm with the earlier studies concerning the identity of the CYP2B6 enzyme...
July 24, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
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