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Dick B S Brashier, Ashok Kumar Sharma, Neha Akhoon
Drug Abuse has become a major challenging problem for the society. It effects people of all countries economical strata's and all ages. According. Monetary loss all over the world regarding drug abuse is in million dollars, it not only has an impact on human productivity and healthcare cost but also on cost of crimes conducted by these drugs and alcohol abuse. Therapeutic vaccine has come as new approach to deal with this problem, after failures in search for a pharmaceutical agent to deal with drug of abuse and alcohol...
September 2016: Indian Journal of Pharmacology
Jeremy S Lum, Francesca Fernandez, Natalie Matosin, Jessica L Andrews, Xu-Feng Huang, Lezanne Ooi, Kelly A Newell
Group 1 metabotropic glutamate receptors (mGluR1/mGluR5) play an integral role in neurodevelopment and are implicated in psychiatric disorders, such as schizophrenia. mGluR1 and mGluR5 are expressed as homodimers, which is important for their functionality and pharmacology. We examined the protein expression of dimeric and monomeric mGluR1α and mGluR5 in the prefrontal cortex (PFC) and hippocampus throughout development (juvenile/adolescence/adulthood) and in the perinatal phencyclidine (PCP) model of schizophrenia...
October 10, 2016: Scientific Reports
The-Vinh Tran, Eun-Joo Shin, Sung Kwon Ko, Yunsung Nam, Yoon Hee Chung, Ji Hoon Jeong, Choon-Gon Jang, Seung-Yeol Nah, Kiyofumi Yamada, Toshitaka Nabeshima, Jae Kyung Byun, Hyoung-Chun Kim
Escalating evidence indicates that ginseng treatment protects against psychotoxic behaviors and memory impairment. Although the underlying mechanism of schizophrenia remains elusive, recent investigations proposed that downregulation of glutathione (GSH) can be involved in the pathogenesis of this disorder. Since little is known about the effects of ginseng in a schizophrenia-like animal model, we selected mountain-cultivated ginseng (MG) from a variety of ginseng extracts to investigate the effect of ginseng on the psychosis induced by phencyclidine (PCP) in mice...
September 26, 2016: Journal of Medicinal Food
Markus R Meyer
This review article covers English-written and PubMed-listed review articles and original studies published between January 2015 and April 2016 dealing with the toxicodynamics and toxicokinetics of new psychoactive substances. Compounds covered include stimulants and entactogens, synthetic cannabinoids, tryptamines, NBOMes, phencyclidine-like drugs, benzodiazepines, and opioids. First, an overview and discussion is provided on timely review articles followed by an overview and discussion on recent original studies...
October 2016: Archives of Toxicology
Gavin P Reynolds, Joanna C Neill
Here, Reynolds and Neill describe the studies that preceded and followed publication of this paper, which reported a deficit in parvalbumin (PV), a calcium-binding protein found in GABA interneurons known to be reduced in schizophrenia patients, in conjunction with a deficit in reversal learning in an animal model for schizophrenia. This publication resulted from common research interests: Reynolds in the neurotransmitter pathology of schizophrenia, and Neill in developing animal models for schizophrenia symptomatology...
September 13, 2016: Journal of Psychopharmacology
Tomohisa Mori, Tsutomu Suzuki
The subjective effects of drugs are related to the kinds of feelings they produce, such as euphoria or dysphoria. One of the methods that can be used to study these effects is the drug discrimination procedure. Many researchers have been trying to elucidate the mechanisms that underlie the discriminative stimulus properties of abused drugs (e.g., alcohol, psychostimulants, and opioids). Over the past two decades, patterns of drug abuse have changed, so that club/recreational drugs such as phencyclidine (PCP), 3,4-methylenedioxymethamphetamine (MDMA), ketamine, and cannabinoid, which induce perceptual distortions, like hallucinations, are now more commonly abused, especially in younger generations...
September 2, 2016: Current Topics in Behavioral Neurosciences
Brandon Stamper, Waseem Gul, Murrell Godfrey, Shahbaz W Gul, Mahmoud A ElSohly
Continuing our previous studies analyzing drugs of abuse in municipal wastewater, a method was developed for the analysis of miscellaneous drugs of abuse in wastewater samples using liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). Eight drugs and metabolites were analyzed including 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrolidine (EDDP), fentanyl, norfentanyl, meperidine, normeperidine, methadone, phencyclidine and tramadol. These drugs were chosen because of their widespread abuse. Wastewater samples were collected at both the Oxford Waste Water Treatment Plant in Oxford, Mississippi (MS) and the University Wastewater Treatment Plant in University, MS...
October 2016: Journal of Analytical Toxicology
P Piyabhan, S Wannasiri, J Naowaboot
Reduced vesicular glutamate transporter 1 (VGLUT1) and 2 (VGLUT2) indicate glutamatergic hypofunction leading to cognitive impairment in schizophrenia. However, VGLUT3 involvement in cognitive dysfunction has not been reported in schizophrenia. Brahmi (Bacopa monnieri) might be new treatment and prevention for cognitive deficit in schizophrenia by affecting on cerebral VGLUT3 density. We aimed to study cognitive-enhancement- and neuroprotective-effects of Brahmi on novel object recognition and cerebral VGLUT3 immunodensity in sub-chronic (2 mg/kg, Bid, ip) phencyclidine (PCP) rat model of schizophrenia...
August 25, 2016: Clinical and Experimental Pharmacology & Physiology
Vincent Cheng, Kenji Inaba, Megan Johnson, Saskya Byerly, Yue Jiang, Kazuhide Matsushima, Tobias Haltmeier, Elizabeth Benjamin, Lydia Lam, Demetrios Demetriades
BACKGROUND: A disproportionately high percentage of trauma patients use controlled substances, and they often co-ingest multiple drugs. Previous studies have evaluated the effect of individual drugs on clinical outcomes after trauma. However, the impact of all drugs included in a comprehensive screening panel has not yet been compared in a single cohort of patients. METHODS: All trauma patients who underwent urine drug screens after admission to the LAC + USC Medical Center (January 2008-June 2015) were identified retrospectively...
November 2016: Journal of Trauma and Acute Care Surgery
Helene A Fachim, Umarat Srisawat, Caroline F Dalton, Michael K Harte, Samuel Marsh, Joanna C Neill, Gavin P Reynolds
AIM: A deficit in parvalbumin neurons is found in schizophrenia and several animal models of the disease. In this preliminary study, we determined whether one such model, phencyclidine (PCP) administration, results in changes in DNA methylation in the rat Pvalb promoter. MATERIALS & METHODS: DNA from hippocampus and prefrontal cortex from rats, which 6 weeks previously received either 2 mg/kg PCP or vehicle for 7 days, underwent bisulphite pyrosequencing to determine methylation...
September 2016: Epigenomics
Vincent L Salgado
Two α-bungarotoxin-sensitive nicotinic acetylcholine (ACh) receptor subtypes in neurons of the American cockroach have been identified as desensitizing (nAChD) and selectively inhibitable with 100nM imidacloprid, and non-desensitizing (nAChN) and selectively inhibitable with 100pM methyllycaconitine. In this paper, the single-electrode voltage-clamp technique was used to measure concentration-response relations for the action of ACh and five antagonists on pharmacologically separated nAChD and nAChN receptors of acutely dissociated neurons from thoracic ganglia of the American cockroach...
September 2016: Neurotoxicology
Fabio Vaiano, Francesco P Busardò, Diego Palumbo, Chrystalla Kyriakou, Alessia Fioravanti, Valeria Catalani, Francesco Mari, Elisabetta Bertol
Identification and quantification of new psychoactive substances (NPS), both in biological and non-biological samples, represent a hard challenge for forensic toxicologists. NPS are increasingly emerging on illegal drug market. Many cases of co-consumption of NPS and other substances have also been reported. Hence, the development of analytical methods aiming at the detection of a broad-spectrum of compounds (NPS and "traditional" drugs) could be helpful. In this paper, a fully validated screening method in blood for the simultaneous detection of 69 substances, including 64 NPS (28 synthetic cannabinoids, 19 synthetic cathinones, 5 phenethylamines, 3 indanes, 2 piperazines, 2 tryptamines, 2 phencyclidine, methoxetamine, ketamine and its metabolite) and 5 amphetamines (amphetamine, methamphetamine, MDMA, MDA, 3,4-methylenedioxy-N-ethylamphetamine - MDEA-) by a dynamic multiple reaction monitoring analysis through liquid chromatography - tandem mass spectrometry (LC-MS/MS) is described...
September 10, 2016: Journal of Pharmaceutical and Biomedical Analysis
Xiao-Wen Chen, Yuan-Yuan Sun, Lei Fu, Jian-Qi Li
A series of novel benzisothiazolylpiperazine derivatives combining potent dopamine D2 and D3, and serotonin 5-HT1A and 5-HT2A receptor properties were synthesized and evaluated for their potential antipsychotic properties. The most-promising derivative was 9j. The unique pharmacological features of 9j were a high affinity for D2, D3, 5-HT1A, and 5-HT2A receptors, together with a 20-fold selectivity for the D3 versus D2 subtype, and a low affinity for muscarinic M1 (reducing the risk of anticholinergic side effects), and for hERG channels (reducing incidence of QT interval prolongation)...
November 10, 2016: European Journal of Medicinal Chemistry
Mona E Hervig, Morten S Thomsen, Imre Kalló, Jens D Mikkelsen
Dysfunction of N-Methyl-d-aspartate receptors (NMDARs) is believed to underlie some of the symptoms in schizophrenia, and non-competitive NMDAR antagonists (including phencyclidine (PCP)) are widely used as pharmacological schizophrenia models. Furthermore, mounting evidence suggests that impaired γ-aminobutyric acid (GABA) neurotransmission contributes to the cognitive deficits in schizophrenia. Thus alterations in GABAergic interneurons have been observed in schizophrenia patients and animal models. Acute systemic administration of PCP increases levels of c-Fos in several cortical and subcortical areas, but whether such induction occurs in specific populations of GABAergic interneuron subtypes still remains to be established...
July 29, 2016: Neuroscience
Linda J Bristow, Amy E Easton, Yu-Wen Li, Digavalli V Sivarao, Regina Lidge, Kelli M Jones, Debra Post-Munson, Christopher Daly, Nicholas J Lodge, Lizbeth Gallagher, Thaddeus Molski, Richard Pieschl, Ping Chen, Adam Hendricson, Ryan Westphal, James Cook, Christiana Iwuagwu, Daniel Morgan, Yulia Benitex, Dalton King, John E Macor, Robert Zaczek, Richard Olson
The development of alpha7 nicotinic acetylcholine receptor agonists is considered a promising approach for the treatment of cognitive symptoms in schizophrenia patients. In the present studies we characterized the novel agent, (2R)-N-(6-(1H-imidazol-1-yl)-4-pyrimidinyl)-4'H-spiro[4-azabicyclo[2.2.2]octane-2,5'-[1,3]oxazol]-2'-amine (BMS-933043), in vitro and in rodent models of schizophrenia-like deficits in cognition and sensory processing. BMS-933043 showed potent binding affinity to native rat (Ki = 3.3 nM) and recombinant human alpha7 nicotinic acetylcholine receptors (Ki = 8...
2016: PloS One
Tommy S Tillman, Frances J D Alvarez, Nathan J Reinert, Chuang Liu, Dawei Wang, Yan Xu, Kunhong Xiao, Peijun Zhang, Pei Tang
Human Cys-loop receptors are important therapeutic targets. High-resolution structures are essential for rational drug design, but only a few are available due to difficulties in obtaining sufficient quantities of protein suitable for structural studies. Although expression of proteins in E. coli offers advantages of high yield, low cost, and fast turnover, this approach has not been thoroughly explored for full-length human Cys-loop receptors because of the conventional wisdom that E. coli lacks the specific chaperones and post-translational modifications potentially required for expression of human Cys-loop receptors...
August 26, 2016: Journal of Biological Chemistry
Philip Lr Gaskin, Maria Toledo-Rodriguez, Stephen Ph Alexander, Kevin Cf Fone
BACKGROUND: Dysfunction of dopaminergic, GABAergic and glutamatergic function underlies many core symptoms of schizophrenia. Combined neonatal injection of the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine (PCP) and post-weaning social isolation of rats produces a behavioral syndrome with translational relevance to several core symptoms of schizophrenia. This study uses DNA microarray to characterise alterations in hippocampal neurotransmitter-related gene expression and examines the ability of the sodium channel blocker, lamotrigine, to reverse behavioral changes in this model...
July 5, 2016: International Journal of Neuropsychopharmacology
Sarah Schumacher, Harald Seitz
An immunoassay was established which enables a reliable quantification of serological drug samples. The assay is based on a competitive ELISA. In total nine drugs (amphetamine, methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA), tetrahydrocannabinol (THC), phencyclidine (PCP), methadone, morphine, cocaine and benzoylecgonine) were tested. All reagents had to pass through a stringent validation process. Within the established test for three out of the nine drugs no cross-reactivity with any tested compounds, e...
September 2016: Journal of Immunological Methods
Erica Bakota, Crystal Arndt, Amelia A Romoser, Stephen K Wilson
We present in this case report a validated method for accurate quantitative analysis of 3-methoxy phencyclidine (3-MeO-PCP) to determine postmortem blood concentrations of this PCP analog. A 29-year-old male with a history of illicit drug use was found unresponsive in his bed with a bag of white powder next to him. Resuscitation efforts were unsuccessful and the individual was pronounced dead 9 minutes after arrival to the hospital. Initial ELISA screening suggested the presence of PCP in the decedent's blood...
September 2016: Journal of Analytical Toxicology
David A Cox, Michael G Gottschalk, Hendrik Wesseling, Agnes Ernst, Jason D Cooper, Sabine Bahn
Pharmacological and genetic rodent models of schizophrenia play an important role in the drug discovery pipeline, but quantifying the molecular similarity of such models with the underlying human pathophysiology has proved difficult. We developed a novel systems biology methodology for the direct comparison of anterior prefrontal cortex tissue from four established glutamatergic rodent models and schizophrenia patients, enabling the evaluation of which model displays the greatest similarity to schizophrenia across different pathophysiological characteristics of the disease...
June 19, 2016: Schizophrenia Research
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