532 results match your criteria Toxicity Phencyclidine


Clozapine Improves Behavioral and Biochemical Outcomes in a MK-801-Induced Mouse Model of Schizophrenia.

J Environ Pathol Toxicol Oncol 2020 ;39(1):1-12

Department of Medical Elementology and Toxicology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India.

Glutamatergic N-methyl-D-aspartate (NMDA) receptors have critical roles in several neurological and psychiatric diseases. Dizocilpine (MK-801) is a ligand at phencyclidine recognition sites that is associated with NMDA receptor-coupled cation channels, where it acts as a potent noncompetitive antagonist of central glutamate receptors. In this study, we investigate the effect of clozapine on MK-801-induced neurochemical and neurobehavioral alterations in the prefrontal cortex of mice. Read More

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http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.2019030362DOI Listing

Intoxication with 3-MeO-PCP alone: A case report and literature review.

Medicine (Baltimore) 2019 Dec;98(52):e18295

CHU Rennes, Department of Forensic Toxicology.

Rationale: 3-Methoxyphencyclidine (3-MeO-PCP) is a new psychoactive substance derived from phencyclidine. Although it can lead to severe intoxications, the main manifestations and optimal management have not been well characterized. Here, we report 2 cases of 3-MeO-PCP intoxication in the same patient, and summarize the manifestations of this intoxication reported in literature. Read More

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http://dx.doi.org/10.1097/MD.0000000000018295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946333PMC
December 2019

Phencyclidine: A Rare Cause of Saccadic Intrusions.

Ann Indian Acad Neurol 2019 Oct-Dec;22(4):503-505. Epub 2019 Oct 25.

Department of Neurology, National Hospital of Sri Lanka, Colombo, Sri Lanka.

Saccadic intrusions such as opsoclonus and ocular flutter are often due to a paraneoplastic or a parainfectious condition. Toxins/drugs may rarely cause them. Herein, we report a rare case of ocular flutter/opsoclonus due to phencyclidine (PCP) toxicity. Read More

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http://dx.doi.org/10.4103/aian.AIAN_174_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839326PMC
October 2019

Focus on Adolescent Use of Club Drugs and "Other" Substances.

Pediatr Clin North Am 2019 12;66(6):1121-1134

Substance Abuse Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, 3901 Chrysler Service Drive, Suite 2A, Detroit, MI 48201, USA.

Club drugs and "other" abusable substances are briefly overviewed as a reminder about the wide variety of known and unknown substances used by adolescents, the high potential for direct and interactive substance use effects to manifest acutely and chronically, and the vigilance needed to anticipate and recognize the new effects and drug-drug interactions arising as novel substances continue to be custom "designed," manufactured, and marketed to meet substance use trends. This article discusses dextromethorphan, flunitrazepam (Rohypnol), gamma-hydroxybutyrate, inhalants, ketamine, lysergic acid diethylamide, methylenedioxymethamphetamine, phencyclidine, Salvia divinorum (salvia), synthetic cannabinoids, and synthetic cathinones (bath salts). Read More

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http://dx.doi.org/10.1016/j.pcl.2019.08.013DOI Listing
December 2019

Severe Toxicity to the New Psychoactive Substances 3-Hydroxyphencyclidine and N-Ethylhexedrone: an Analytically Confirmed Case Report.

J Med Toxicol 2020 Jan 3;16(1):67-70. Epub 2019 Sep 3.

Guys and St Thomas' NHS Foundation, Faculty of Life Sciences and Medicine, King's College London, London, UK.

Introduction: 3-Hydroxyphencyclidine (3-HO-PCP) is a new psychoactive substance (NPS) and a hydroxy derivative of phencyclidine (PCP), and N-ethylhexedrone (Hexen) is a synthetic cathinone. We describe an analytically confirmed case of acute toxicity related to the use of both 3-hydroxyphencyclidine and N-ethylhexedrone.

Case Report: A 56-year-old male was brought to the Emergency Department by ambulance with hyperthermia (39. Read More

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http://link.springer.com/10.1007/s13181-019-00734-x
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http://dx.doi.org/10.1007/s13181-019-00734-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942087PMC
January 2020
6 Reads

SEP-363856, a Novel Psychotropic Agent with a Unique, Non-D Receptor Mechanism of Action.

J Pharmacol Exp Ther 2019 10 1;371(1):1-14. Epub 2019 Aug 1.

Sunovion Pharmaceuticals, Marlborough, Massachusetts (N.D., P.G.J., S.C.H., R.L., L.S., J.E.C., K.L.S., T.H.L., U.C.C., K.S.K.); and PsychoGenics, Paramus, New Jersey (T.H., E.L.)

For the past 50 years, the clinical efficacy of antipsychotic medications has relied on blockade of dopamine D receptors. Drug development of non-D compounds, seeking to avoid the limiting side effects of dopamine receptor blockade, has failed to date to yield new medicines for patients. In this work, we report the discovery of SEP-363856 (SEP-856), a novel psychotropic agent with a unique mechanism of action. Read More

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http://dx.doi.org/10.1124/jpet.119.260281DOI Listing
October 2019
3 Reads

Novel ketamine analogues cause a false positive phencyclidine immunoassay.

Ann Clin Biochem 2019 09 25;56(5):598-607. Epub 2019 Jun 25.

1 Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

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http://dx.doi.org/10.1177/0004563219858125DOI Listing
September 2019
2 Reads

Blonanserin ameliorates social deficit through dopamine-D receptor antagonism in mice administered phencyclidine as an animal model of schizophrenia.

Neurochem Int 2019 09 16;128:127-134. Epub 2019 Apr 16.

Division of Clinical Sciences and Neuropsychopharmacology, Faculty of Pharmacy, Meijo University, Nagoya, 468-8503, Japan; Division of Clinical Sciences and Neuropsychopharmacology, Graduate School of Pharmacy, Meijo University, Nagoya, 468-8503, Japan; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, 466-8560, Japan. Electronic address:

Blonanserin differs from other antipsychotic drugs, such as risperidone and olanzapine, and exhibits a higher affinity for dopamine-D receptors than for serotonin 5-HT receptors. We investigated the involvement of dopamine-D receptors in the effect of blonanserin on the social deficit observed in an animal model of schizophrenia and sought to elucidate the molecular mechanism underlying its action. Mice received phencyclidine (PCP: 10 mg/kg/day, s. Read More

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http://dx.doi.org/10.1016/j.neuint.2019.04.008DOI Listing
September 2019
1 Read

Chronic phencyclidine treatment impairs spatial working memory in rhesus monkeys.

Psychopharmacology (Berl) 2019 Jul 25;236(7):2223-2232. Epub 2019 Mar 25.

Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.

Rationale: Phencyclidine (PCP) could induce schizophrenia (Sz) like behavior in both humans and animals, therefore, has been widely utilized to establish Sz animal models. It induced cognitive deficits, the core symptom of Sz, mainly through influencing frontal dopaminergic function. Nonhuman primate (NHP) studies demonstrated impaired object retrieval detour (ORD) and spatial delayed response (SDR) task performance by acute or chronic PCP treatment. Read More

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http://link.springer.com/10.1007/s00213-019-05214-2
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http://dx.doi.org/10.1007/s00213-019-05214-2DOI Listing
July 2019
31 Reads

Linking phencyclidine intoxication to the tryptophan-kynurenine pathway: Therapeutic implications for schizophrenia.

Neurochem Int 2019 05 5;125:1-6. Epub 2019 Feb 5.

Department of Disease Control and Prevention, Fujita Health University Graduate School of Health Sciences, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan; Japanese Drug Organization of Appropriate Use and Research, 3-1509 Omoteyama, Tenpaku-ku, Nagoya, Aichi 468-0069, Japan; Advanced Diagnostic System Research Laboratory, Fujita Health University Graduate School of Health Sciences, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan; Human Health Sciences, Graduate School of Medicine and Faculty of Medicine, Kyoto University, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.

Phencyclidine (PCP) is a dissociative anesthetic that induces psychotic symptoms and neurocognitive deficits in rodents similar to those observed in schizophrenia patients. PCP administration in healthy human subjects induces schizophrenia-like symptoms such as positive and negative symptoms, and a range of cognitive deficits. It has been reported that PCP, ketamine, and related drugs such as N-methyl-D-aspartate-type (NMDA) glutamate receptor antagonists, induce behavioral effects by blocking neurotransmission at NMDA receptors. Read More

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http://dx.doi.org/10.1016/j.neuint.2019.02.001DOI Listing
May 2019
18 Reads

Continuation of structure-activity relationship study of novel benzamide derivatives as potential antipsychotics.

Arch Pharm (Weinheim) 2019 Apr 31;352(4):e1800306. Epub 2019 Jan 31.

University of Chinese Academy of Sciences, Beijing, China.

A series of benzamide derivatives possessing potent dopamine D , serotonin 5-HT , and 5-HT receptor properties were synthesized and evaluated as potential antipsychotics. Among them, 5-(4-(4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)butoxy)-N-cyclopropyl-2-fluorobenzamide (4k) held the best pharmacological profile. It not only exhibited potent and balanced activities for the D , 5-HT , and 5-HT receptors, but was also endowed with low to moderate activities for the 5-HT , H , and M receptors, suggesting a low propensity for inducing weight gain or diabetes. Read More

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http://dx.doi.org/10.1002/ardp.201800306DOI Listing
April 2019
7 Reads
1.396 Impact Factor

Suspected synthetic cannabinoid receptor agonist intoxication: Does analysis of samples reflect the presence of suspected agents?

Am J Emerg Med 2019 10 24;37(10):1846-1849. Epub 2018 Dec 24.

Georgetown University School of Medicine, Washington, DC, United States of America; Department of Emergency Medicine, MedStar Washington Hospital Center, Washington, DC, United States of America.

Background: There has been a surge in synthetic cannabinoid receptor agonist (SCRA) exposures reported in recent years. The constituents of SCRA preparations are constantly evolving and rarely confirmed. We sought to characterize the constituents of reported SCRA exposures presenting to the emergency department (ED). Read More

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http://dx.doi.org/10.1016/j.ajem.2018.12.044DOI Listing
October 2019
1 Read

Reduced expression of synapsin II in a chronic phencyclidine preclinical rat model of schizophrenia.

Synapse 2019 05 7;73(5):e22084. Epub 2019 Jan 7.

Faculty of Health Sciences, Department of Psychiatry and Behavioral Neuroscience, McMaster University, Hamilton, Ontario, Canada.

Schizophrenia is a mental disorder characterized by positive symptoms, negative symptoms, and cognitive dysfunction. Phencyclidine (PCP)-a N-methyl-D-aspartate (NMDA) receptor antagonist-induces symptoms indistinguishable from those of schizophrenia. A reduction of the phosphoprotein synapsin II has also been implicated in schizophrenia and has a well-known role in the maintenance of the presynaptic reserve pool and vesicle mobilization. Read More

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http://dx.doi.org/10.1002/syn.22084DOI Listing
May 2019
6 Reads

Selective adrenergic alpha2C receptor antagonist ameliorates acute phencyclidine-induced schizophrenia-like social interaction deficits in rats.

Psychopharmacology (Berl) 2019 Apr 10;236(4):1245-1253. Epub 2018 Dec 10.

School of Pharmacy, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland.

Rationale: Social withdrawal is a core feature of the negative symptoms of schizophrenia. Currently available pharmacotherapies have only limited efficacy towards the negative symptoms, i.e. Read More

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http://link.springer.com/10.1007/s00213-018-5130-2
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http://dx.doi.org/10.1007/s00213-018-5130-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591184PMC
April 2019
3 Reads

Methoxetamine Induces Cytotoxicity in H9c2 Cells: Possible Role of p21 Protein (Cdc42/Rac)-Activated Kinase 1.

Cardiovasc Toxicol 2019 06;19(3):229-236

College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31 Osongsaemgmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju-si, Chungbuk, 28160, Republic of Korea.

The abuse of new psychoactive substances (NPS) is an emerging social problem. Methoxetamine, one of the NPS, was designed as an alternative to ketamine and it was considered an NPS candidate owing to its high addictive potential. However, cardiotoxicity of the phencyclidine analogue, methoxetamine, has not been extensively evaluated. Read More

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http://dx.doi.org/10.1007/s12012-018-9489-4DOI Listing
June 2019
12 Reads

Methoxetamine: A foe or friend?

Neurochem Int 2019 01 24;122:1-7. Epub 2018 Oct 24.

Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, 815 Hwarangro, Nowon-gu, Seoul, 01795, Republic of Korea. Electronic address:

Methoxetamine (MXE) is an N-methyl-D-aspartate (NMDA) receptor antagonist that is chemically and pharmacologically similar to other dissociative substances, such as ketamine and phencyclidine. There are reports on the misuse of MXE, which sometimes resulted in adverse consequences and death. Studies have also shown that MXE has abuse liability and stimulates dopamine neurotransmission in the mesolimbic reward pathway in the brain. Read More

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http://dx.doi.org/10.1016/j.neuint.2018.10.020DOI Listing
January 2019
11 Reads

The effects of donepezil on phencyclidine-induced cognitive deficits in a mouse model of schizophrenia.

Pharmacol Biochem Behav 2018 12 12;175:69-76. Epub 2018 Sep 12.

Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

Donepezil is the first-line of treatment for Alzheimer's disease (AD), which improves cognitive impairment effectively, but whether it has an impact on cognitive impairment in schizophrenia remains unknown. In this study, we evaluated the effects and mechanisms of donepezil on schizophrenia-like cognitive deficits induced by phencyclidine (PCP). The cognitive deficits model of schizophrenia was established by injecting PCP into mice. Read More

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http://dx.doi.org/10.1016/j.pbb.2018.09.006DOI Listing
December 2018
5 Reads

Role of mGlu2 in the 5-HT receptor-dependent antipsychotic activity of clozapine in mice.

Psychopharmacology (Berl) 2018 Nov 12;235(11):3149-3165. Epub 2018 Sep 12.

Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA.

Background: Serotonin 5-HT and metabotropic glutamate 2 (mGlu2) are neurotransmitter G protein-coupled receptors (GPCRs) involved in the signaling mechanisms underlying psychosis and schizophrenia treatment. Previous findings in mGlu2 knockout (KO) mice suggested that mGlu2 is necessary for head-twitch behavior, a rodent phenotype characteristic of hallucinogenic 5-HT receptor agonists. However, the role of mGlu2 in the behavioral effects induced by antipsychotic drugs remains poorly understood. Read More

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http://dx.doi.org/10.1007/s00213-018-5015-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408231PMC
November 2018
14 Reads

Clozapine attenuates mitochondrial burdens and abnormal behaviors elicited by phencyclidine in mice via inhibition of p47 ; Possible involvements of phosphoinositide 3-kinase/Akt signaling.

J Psychopharmacol 2018 11 12;32(11):1233-1251. Epub 2018 Sep 12.

1 Neuropsychopharmacology and Toxicology Program, Kangwon National University, Chunchon, Republic of Korea.

Background: Oxidative stress and mitochondrial dysfunction have been implicated in the pathophysiology of schizophrenia.

Aims: We investigated whether antipsychotic clozapine modulates nicotinamide adenine dinucleotide phosphate oxidase and mitochondrial burdens induced by phencyclidine in mice.

Methods: We examined the effect of clozapine on nicotinamide adenine dinucleotide phosphate oxidase activation, mitochondrial burdens (i. Read More

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http://journals.sagepub.com/doi/10.1177/0269881118795244
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http://dx.doi.org/10.1177/0269881118795244DOI Listing
November 2018
66 Reads
3.593 Impact Factor

1,2-Diarylethylamine- and Ketamine-Based New Psychoactive Substances.

Handb Exp Pharmacol 2018;252:305-352

School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.

While phencyclidine (PCP) and ketamine remain the most well-studied and widely known dissociative drugs, a number of other agents have appeared since the late 1950s and early 1960s, when the pharmacological potential of this class was first realized. For example, hundreds of compounds have been pursued as part of legitimate research efforts to explore these agents. Some of these found their way out of the research labs and onto illicit markets of the 1960s and following decades as PCP analogs. Read More

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http://link.springer.com/10.1007/164_2018_148
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http://dx.doi.org/10.1007/164_2018_148DOI Listing
June 2019
63 Reads

TPA-023 attenuates subchronic phencyclidine-induced declarative and reversal learning deficits via GABA receptor agonist mechanism: possible therapeutic target for cognitive deficit in schizophrenia.

Neuropsychopharmacology 2018 11 23;43(12):2468-2477. Epub 2018 Jul 23.

Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.

GABAergic drugs are of interest for the treatment of anxiety, depression, bipolar disorder, pain, cognitive impairment associated with schizophrenia (CIAS), and other neuropsychiatric disorders. Some evidence suggests that TPA-023, (7-(1,1-dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b] pyridazine), a GABA α2,3 subtype-selective GABA partial agonist and α antagonist, and the neurosteroid, pregnenolone sulfate, a GABA antagonist, may improve CIAS in pilot clinical trials. The goal of this study was to investigate the effect of TPA-023 in mice after acute or subchronic (sc) treatment with the N-methyl-D-aspartate receptor (NMDAR) antagonist, phencyclidine (PCP), on novel object recognition (NOR), reversal learning (RL), and locomotor activity (LMA) in rodents. Read More

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http://www.nature.com/articles/s41386-018-0160-3
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http://dx.doi.org/10.1038/s41386-018-0160-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180114PMC
November 2018
42 Reads

Cluster of acute poisonings associated with an emerging ketamine analogue, 2-oxo-PCE.

Forensic Sci Int 2018 Sep 24;290:238-243. Epub 2018 Jul 24.

Hospital Authority Toxicology Reference Laboratory, Princess Margaret Hospital, Hong Kong; Chemical Pathology Laboratory, Princess Margaret Hospital, Hong Kong. Electronic address:

Ketamine and phencyclidine are well-known drugs of abuse of the arylcyclohexylamine class, the backbone of which is used for the synthesis of new psychoactive substances (NPS). In October 2017, a cluster of acute intoxications was encountered where patients presented with ketamine-like toxidrome. Upon initial toxicology screening, however, neither ketamine nor other causative agents were detected in the patients' urine. Read More

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http://dx.doi.org/10.1016/j.forsciint.2018.07.014DOI Listing
September 2018
14 Reads

5-HT parital agonism and 5-HT antagonism restore episodic memory in subchronic phencyclidine-treated mice: role of brain glutamate, dopamine, acetylcholine and GABA.

Psychopharmacology (Berl) 2018 Oct 31;235(10):2795-2808. Epub 2018 Jul 31.

Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave., Ward Building 7-014, Chicago, IL, 60611, USA.

Rationale: The effect of atypical antipsychotic drugs (AAPDs), e.g., lurasidone, to improve cognitive impairment associated with schizophrenia (CIAS), has been suggested to be due, in part, to enhancing release of dopamine (DA), acetylcholine (ACh), and glutamate (Glu) in cortex and hippocampus. Read More

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http://dx.doi.org/10.1007/s00213-018-4972-yDOI Listing
October 2018
40 Reads

Effects of the Dopamine Stabilizer, Pridopidine, on Basal and Phencyclidine-Induced Locomotion: Role of Dopamine D2 and Sigma-1 Receptors.

CNS Neurol Disord Drug Targets 2018 ;17(7):522-527

Unitat de Farmacologia, Departament Patologia i Terapeutica Experimental, Facultat de Medicina i Ciencies de la Salut, IDIBELL-Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.

Background: Pridopidine, a compound in clinical trials for Huntington's disease treatment, was originally synthesized as a dopamine D2 receptor (D2R) ligand, but later found to possess higher affinity for the sigma-1 receptor (S1R). However, the putative contributions of D2R and S1R to the behavioral profile of acutely administered pridopidine have not been investigated.

Objective: The present study sought to compare the effects of acute pridopidine on wild-type vs. Read More

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http://dx.doi.org/10.2174/1871527317666180627103337DOI Listing
October 2019
25 Reads

Attenuation of toluene-induced brain stimulation reward enhancement and behavioral disturbances by N-acetylcysteine in mice.

Toxicology 2018 09 21;408:39-45. Epub 2018 Jun 21.

Pharmacology and Toxicology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, 97004, Taiwan; Center for Neuropsychiatric Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan; Research Center for Mind, Brain, and Learning, National Chengchi University, 64, Sec. 2, ZhiNan Road, Wenshan District, Taipei City 11605, Taiwan. Electronic address:

Toluene, a commonly used organic solvent, produces a variety of behavioral disturbances in both humans and animals comparable to noncompetitive N-methyl-D-aspartate receptor (NMDARs) antagonists, such as phencyclidine (PCP). N-acetylcysteine (NAC) is capable of reversing the psychotomimetic effects of PCP via activation of cystine-glutamate antiporters (xCT). The present study examined whether NAC is capable of attenuating the toluene-induced brain stimulation reward enhancement and behavioral manifestations. Read More

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http://dx.doi.org/10.1016/j.tox.2018.06.011DOI Listing
September 2018
48 Reads

Phencyclidine and Scopolamine for Modeling Amnesia in Rodents: Direct Comparison with the Use of Barnes Maze Test and Contextual Fear Conditioning Test in Mice.

Neurotox Res 2018 Oct 21;34(3):431-441. Epub 2018 Apr 21.

Department of Pharmacodynamics, Chair of Pharmacodynamics, Jagiellonian University Medical College, 9 Medyczna St., 30 - 688, Krakow, Poland.

Nowadays cognitive impairments are a growing unresolved medical issue which may accompany many diseases and therapies, furthermore, numerous researchers investigate various neurobiological aspects of human memory to find possible ways to improve it. Until any other method is discovered, in vivo studies remain the only available tool for memory evaluation. At first, researchers need to choose a model of amnesia which may strongly influence observed results. Read More

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http://dx.doi.org/10.1007/s12640-018-9901-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154175PMC
October 2018
11 Reads

Effects of cariprazine on extracellular levels of glutamate, GABA, dopamine, noradrenaline and serotonin in the medial prefrontal cortex in the rat phencyclidine model of schizophrenia studied by microdialysis and simultaneous recordings of locomotor activity.

Psychopharmacology (Berl) 2018 05 11;235(5):1593-1607. Epub 2018 Apr 11.

Allergan, Madison, NJ, USA.

Rationale: Aberrant glutamatergic, dopaminergic, and GABAergic neurotransmission has been implicated in schizophrenia. Cariprazine reverses the behavioral effects observed in the rat phencyclidine (PCP)-induced model of schizophrenia; however, little is known about its in vivo neurochemistry.

Objectives: The study aims to compare the effects of cariprazine and aripiprazole on PCP-induced changes in the extracellular levels of glutamate, dopamine, serotonin, noradrenaline, and GABA in the rat medial prefrontal cortex (mPFC), and on locomotor activation. Read More

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http://dx.doi.org/10.1007/s00213-018-4874-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920013PMC
May 2018
35 Reads

Toxicokinetics of NPS: Update 2017.

Authors:
Markus R Meyer

Handb Exp Pharmacol 2018;252:441-459

Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, Homburg, Germany.

This summarizing and descriptive review article is an update on previously published reviews. It covers English-written and PubMed-listed review articles and original studies published between May 2016 and November 2017 on the toxicokinetics of new psychoactive substances (NPS). Compounds covered include stimulants and entactogens, synthetic cannabinoids, tryptamines, phenethylamine and phencyclidine-like drugs, benzodiazepines, and opioids. Read More

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http://dx.doi.org/10.1007/164_2018_102DOI Listing
June 2019
45 Reads

The Effects of Cariprazine and Aripiprazole on PCP-Induced Deficits on Attention Assessed in the 5-Choice Serial Reaction Time Task.

Psychopharmacology (Berl) 2018 05 22;235(5):1403-1414. Epub 2018 Feb 22.

Gedeon Richter Plc, Budapest, Hungary.

Rationale: Attentional processing deficits are a core feature of schizophrenia, likely contributing to the persistent functional and occupational disability observed in patients with schizophrenia. The pathophysiology of schizophrenia is hypothesized to involve dysregulation of NMDA receptor-mediated glutamate transmission, contributing to disruptions in normal dopamine transmission. Preclinical investigations often use NMDA receptor antagonists, such as phencyclidine (PCP), to induce cognitive disruptions relevant to schizophrenia. Read More

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http://dx.doi.org/10.1007/s00213-018-4857-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920008PMC
May 2018
27 Reads

Effects of selective calcium-permeable AMPA receptor blockade by IEM 1460 on psychotomimetic-induced hyperactivity in the mouse.

J Neural Transm (Vienna) 2018 04 21;125(4):705-711. Epub 2017 Dec 21.

Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.

Diminished glutamate neurotransmission via the N-methyl-D-aspartate type glutamate receptor (NMDAR) has been considered to be involved in the pathophysiology of schizophrenia based upon the observation that the antagonists and autoantibodies of NMDAR cause positive, negative and cognitive symptomatologies similar to those of schizophrenia. The possible reduced extracellular levels of D-serine by overstimulation of the calcium-permeable α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate glutamate receptor (CP-AMPAR) following the NMDAR hypofunction-induced compensatory increase in the glutamate release could aggravate the NMDAR hypofunction in the brain of the drug- or antibody-associated psychoses and schizophrenia, because D-serine is an intrinsic coagonist for the NMDAR. To obtain an insight into the therapeutic approach to such a glutamate-linked psychotic state, we have studied the effects of the systemic administration of the CP-AMPAR-selective antagonist, IEM 1460 (N,N,N-trimethyl-5- [(tricyclo[3. Read More

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http://dx.doi.org/10.1007/s00702-017-1827-3DOI Listing
April 2018
67 Reads

Mechanistic studies on ketamine-induced mitochondrial toxicity in zebrafish embryos.

Neurotoxicol Teratol 2018 Sep - Oct;69:63-72. Epub 2017 Dec 7.

Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA. Electronic address:

Ketamine, a phencyclidine derivative, is an antagonist of the Ca-permeable N-methyl-d-aspartate (NMDA)-type glutamate receptors. It is a pediatric anesthetic and has been implicated in developmental neurotoxicity. Ketamine has also been shown to deplete ATP in mammalian cells. Read More

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http://dx.doi.org/10.1016/j.ntt.2017.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992061PMC
October 2019
15 Reads

Blockade of platelet-activating factor receptor attenuates abnormal behaviors induced by phencyclidine in mice through down-regulation of NF-κB.

Brain Res Bull 2018 03 7;137:71-78. Epub 2017 Nov 7.

Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, Republic of Korea. Electronic address:

Accumulating evidence suggests that neuroinflammation is one of the important etiologic factors of abusive and neuropsychiatric disorders. Platelet-activating factor (PAF) is potent proinflammatory lipid mediat1or and plays a pivotal role in neuroinflammatory disorders through the specific PAF receptor (PAF-R). Phencyclidine (PCP) induces a psychotomimetic state that closely resembles schizophrenia. Read More

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http://dx.doi.org/10.1016/j.brainresbull.2017.11.004DOI Listing
March 2018
35 Reads

Phencyclidine Discoordinates Hippocampal Network Activity But Not Place Fields.

J Neurosci 2017 12 8;37(49):12031-12049. Epub 2017 Nov 8.

Department of Physiology and Pharmacology, State University of New York, Downstate Medical Center,

We used the psychotomimetic phencyclidine (PCP) to investigate the relationships among cognitive behavior, coordinated neural network function, and information processing within the hippocampus place cell system. We report in rats that PCP (5 mg/kg, i.p. Read More

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http://dx.doi.org/10.1523/JNEUROSCI.0630-17.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5719978PMC
December 2017
21 Reads

Significance of the nicotinic alpha7 receptor in cognition and antipsychotic-like behavior in the rat.

Behav Brain Res 2017 08 3;333:129-134. Epub 2017 Jul 3.

Department of Basic Sciences, California Northstate University College of Medicine, CA, USA.

Schizophrenic (SCH) patients show cognitive impairment in attentional performance. Positive allosteric modulators (PAMs) of α7 nicotinic acetylcholine receptors (nAChRs) such as the Alzheimer's drug galantamine (GAL) and PAM-2 are documented to have pro-cognitive properties. However, it is not well established if these properties would be lost, or may hamper antipsychotic efficacy, when given as an adjunct to an antipsychotic which is needed for managing psychotic symptoms. Read More

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http://dx.doi.org/10.1016/j.bbr.2017.07.001DOI Listing
August 2017
21 Reads

Beyond Ketamine and Phencyclidine: Analytically Confirmed Use of Multiple Novel Arylcyclohexylamines.

J Psychoactive Drugs 2017 Sep-Oct;49(4):289-293. Epub 2017 Jun 7.

c Assistant Professor, Department of Laboratory Medicine , University of California-San Francisco, San Francisco General Hospital , San Francisco , CA , USA.

Background: Methoxetamine and 3-methoxy-phencyclidine are novel arylcyclohexylamines whose use and clinical toxicity are poorly reported in the medical literature. We report a case of analytically confirmed use of both methoxetamine and 3-methoxy-phencyclidine.

Case Report: A 27-year-old male presented 10 hours after insufflating an Internet-obtained powder. Read More

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http://dx.doi.org/10.1080/02791072.2017.1333660DOI Listing
May 2018
74 Reads

Phencyclidine administration during neurodevelopment alters network activity in prefrontal cortex and hippocampus in adult rats.

J Neurophysiol 2017 08 24;118(2):1002-1011. Epub 2017 May 24.

Lundbeck Research DK, H. Lundbeck A/S, Valby, Denmark; and.

Symptoms of schizophrenia have been linked to insults during neurodevelopment such as NMDA receptor (NMDAR) antagonist exposure. In animal models, this leads to schizophrenia-like behavioral symptoms as well as molecular and functional changes within hippocampal and prefrontal regions. The aim of this study was to determine how administration of the NMDAR antagonist phencyclidine (PCP) during neurodevelopment affects functional network activity within the hippocampus and medial prefrontal cortex (mPFC). Read More

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http://dx.doi.org/10.1152/jn.00081.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5539451PMC
August 2017
29 Reads

Generation of the Acute Phencyclidine Rat Model for Proteomic Studies of Schizophrenia.

Authors:
Dan Ma Paul C Guest

Adv Exp Med Biol 2017 ;974:257-261

Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Rua Monteiro Lobato 255 F/01, Cidade Universitária Zeferino Vaz, 13083-862, Campinas, Brazil.

Administration of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist phencyclidine (PCP) to rodents has been used as the gold standard preclinical model for schizophrenia. PCP treatment induces hyperlocomotion and stereotypic behaviour, which resemble the positive symptoms of schizophrenia. In addition, proteomic studies have identified changes in proteins associated with energy metabolism and neurotransmission which are typical hallmarks of the disease. Read More

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http://dx.doi.org/10.1007/978-3-319-52479-5_23DOI Listing
September 2017
25 Reads

Dose-response effect of acute phencyclidine on functional connectivity and dopamine levels, and their association with schizophrenia-like symptom classes in rat.

Neuropharmacology 2017 06 22;119:15-25. Epub 2017 Mar 22.

A.I.V. Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland.

Current drug treatments for schizophrenia (SCZ) can alleviate positive symptoms, but have little effect on the negative symptoms and cognitive deficits that are difficult to translate into preclinical models for drug development. Therefore, we aimed to determine the dose-response effects of acute phencyclidine (PCP, 1.0-5. Read More

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http://dx.doi.org/10.1016/j.neuropharm.2017.03.024DOI Listing
June 2017
15 Reads

Altered cortico-striatal crosstalk underlies object recognition memory deficits in the sub-chronic phencyclidine model of schizophrenia.

Brain Struct Funct 2017 Sep 14;222(7):3179-3190. Epub 2017 Mar 14.

Department of Neuroscience, Psychology and Behaviour, University of Leicester, Leicester, LE1 9HN, UK.

The neural mechanisms underlying cognitive deficits in schizophrenia are poorly understood. Sub-chronic treatment with the NMDA antagonist phencyclidine (PCP) produces cognitive abnormalities in rodents that reliably model aspects of the neurocognitive alterations observed in schizophrenia. Given that network activity across regions encompassing medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) plays a significant role in motivational and cognitive tasks, we measured activity across cortico-striatal pathways in PCP-treated rats to characterize neural enabling and encoding of task performance in a novel object recognition task. Read More

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http://dx.doi.org/10.1007/s00429-017-1393-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585296PMC
September 2017
15 Reads

Preclinical predictors that the orthosteric mGlu2/3 receptor antagonist LY3020371 will not engender ketamine-associated neurotoxic, motor, cognitive, subjective, or abuse-liability-related effects.

Pharmacol Biochem Behav 2017 04 8;155:43-55. Epub 2017 Mar 8.

Windlesham, Surrey, UK. Electronic address:

The novel mGlu2/3 receptor antagonist, LY3020371, has been shown to produce antidepressant-like effects comparable to that of the clinically-effective antidepressant ketamine. In the present study, we investigated whether LY3020371 would be predicted to be free of the side-effects and safety pharmacology issues associated with ketamine. In contrast to ketamine, LY3020371 produced small increases in locomotion and did not impair motor performance on an inverted screen. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00913057173000
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http://dx.doi.org/10.1016/j.pbb.2017.03.001DOI Listing
April 2017
18 Reads

Alterations of ubiquitin related proteins in the pathology and development of schizophrenia: Evidence from human and animal studies.

J Psychiatr Res 2017 07 18;90:31-39. Epub 2017 Jan 18.

Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, Australia; Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW 2522, Australia; Schizophrenia Research Institute, Sydney, NSW 2010, Australia; Faculty of Social Sciences, University of Wollongong, Wollongong, NSW 2522, Australia. Electronic address:

Gene expression analyses in post-mortem schizophrenia brains suggest that a number of ubiquitin proteasome system (UPS) genes are associated with schizophrenia; however the status of UPS proteins in the schizophrenia brain is largely unknown. Ubiquitin related proteins are inherently involved in memory, neuronal survival and morphology, which are processes implicated in neurodevelopmental disorders such as schizophrenia. We examined levels of five UPS proteins (Protein Inhibitor of Activated STAT2 [PIAS2], F-Box and Leucine rich repeat protein 21 [FBXL21], Mouse Double Minute 2 homolog [MDM2], Ubiquitin Carboxyl-Terminal Hydrolase-L1 [UCHL1] and Ubiquitin Conjugating Enzyme E2D1 [UBE2D1]) involved in these neuronal processes, within the dorsolateral prefrontal cortex of post-mortem schizophrenia subjects and matched controls (n = 30/group), in addition to across neurodevelopmental time-points (juvenile, adolescent and adult stages of life), utilizing a well-established neurodevelopmental phencyclidine (PCP) animal model of schizophrenia. Read More

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http://dx.doi.org/10.1016/j.jpsychires.2017.01.009DOI Listing
July 2017
28 Reads

Metabolism and metabolomics of ketamine: a toxicological approach.

Forensic Sci Res 2017 20;2(1):2-10. Epub 2017 Feb 20.

Department of Sciences, IINFACTS - Institute of Research and Advanced Training in Health Sciences and Technologies, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal.

Ketamine is a phencyclidine derivative and a non-competitive antagonist of -methyl--aspartate (NMDA) receptor for which glutamate is the full agonist. It produces a functional dissociation between the thalamocortical and limbic systems, a state that has been termed as dissociative anaesthesia. Considerable variability in the pharmacokinetics and pharmacodynamics between individuals that can affect dose-response and toxicological profile has been reported. Read More

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https://www.tandfonline.com/doi/full/10.1080/20961790.2017.1
Publisher Site
http://dx.doi.org/10.1080/20961790.2017.1285219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197107PMC
February 2017
52 Reads

Effects of Repeated Ropinirole Treatment on Phencyclidine-Induced Hyperlocomotion, Prepulse Inhibition Deficits, and Social Avoidance in Rats.

J Pharmacol Exp Ther 2017 04 6;361(1):109-114. Epub 2017 Feb 6.

Department of Basic Medical Sciences (A.M.M., P.C.K., R.P.H.), and Departments of Pharmacology and Psychiatry (R.P.H.), University of Arizona College of Medicine, Phoenix; and Department of Psychology (A.M.M., P.C.K., R.P.H.) and Interdisciplinary Graduate Program in Neuroscience (T.C., R.P.H.), Arizona State University, Tempe, Arizona

Phencyclidine (PCP), a noncompetitive N-methyl d-aspartate (NMDA) receptor antagonist, provides the most complete pharmacologic model of schizophrenia in humans and animals. Acute PCP causes hyperlocomotion, disrupts prepulse inhibition (PPI), and increases social avoidance in rats. We have previously shown that repeated treatment with the dopamine (DA) D-like receptor agonists, quinpirole or ropinirole, prevents agonist-induced PPI disruption. Read More

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http://jpet.aspetjournals.org/lookup/doi/10.1124/jpet.116.23
Publisher Site
http://dx.doi.org/10.1124/jpet.116.238634DOI Listing
April 2017
11 Reads

Two Cases of Non-fatal Intoxication with a Novel Street Hallucinogen: 3-Methoxy-Phencyclidine.

J Anal Toxicol 2017 May;41(4):350-354

Institute Forensic Medicine and Toxicology, First Faculty of Medicine, Charles University and General University Hospital, Ke Karlovu 2, Prague 2, Prague.

3-Methoxy-phencyclidine (3-MeO-PCP) is a structural derivative of the dissociative hallucinogen phencyclidine (PCP). Although PCP toxicity is well documented, little is known about this new psychoactive substance despite being available on the black market even in central Europe. The objective of this case report is to present clinical and laboratory data of analytically confirmed non-fatal intoxication of two subjects with 3-MeO-PCP. Read More

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http://dx.doi.org/10.1093/jat/bkx009DOI Listing
May 2017
62 Reads

3-MeO-PCP intoxication in two young men: First in vivo detection in Italy.

Forensic Sci Int 2017 May 26;274:7-12. Epub 2016 Dec 26.

Forensic Toxicology Division, Department of Health Science, University of Florence, Italy. Electronic address:

3-MeO-PCP or 3-methoxyphencyclidine is a derivative of phencyclidine. It acts as a dissociative anesthetic and it has allegedly hallucinogenic and sedative effects. There are almost no documented intoxication cases and references about its pharmacology and toxicity in literature. Read More

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http://dx.doi.org/10.1016/j.forsciint.2016.12.028DOI Listing
May 2017
35 Reads

The prolyl oligopeptidase inhibitor IPR19 ameliorates cognitive deficits in mouse models of schizophrenia.

Eur Neuropsychopharmacol 2017 02 14;27(2):180-191. Epub 2016 Dec 14.

Department of Pharmacology, University of the Basque Country UPV/EHU, BioCruces Health Research Institute, Spain; Centro de Investigación Biomédica en Red de Salud Mental CIBERSAM, Spain. Electronic address:

Cognitive deficits are considered a key feature of schizophrenia, and they usually precede the onset of the illness and continue after psychotic symptoms appear. Current antipsychotic drugs have little or no effect on the cognitive deficits of this disorder. Prolyl oligopeptidase (POP) is an 81-kDa monomeric serine protease that is expressed in brain and other tissues. Read More

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http://dx.doi.org/10.1016/j.euroneuro.2016.11.016DOI Listing
February 2017
22 Reads

Effects of a non-competitive N-methyl-d-aspartate (NMDA) antagonist, tiletamine, in adult zebrafish.

Neurotoxicol Teratol 2017 Jan - Feb;59:62-67. Epub 2016 Dec 2.

Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, Russia. Electronic address:

Tiletamine is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist chemically related to ketamine and phencyclidine. A common veterinary anesthetic drug, tiletamine is currently a Schedule III controlled substance in USA. This compound exerts sedative effects in humans and animals, also having an abuse potential, toxicity and dissociative hallucinogenic properties clinically. Read More

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http://dx.doi.org/10.1016/j.ntt.2016.11.009DOI Listing
January 2018
24 Reads

Distinct cortical and striatal actions of a β-arrestin-biased dopamine D2 receptor ligand reveal unique antipsychotic-like properties.

Proc Natl Acad Sci U S A 2016 12 1;113(50):E8178-E8186. Epub 2016 Dec 1.

Department of Cell Biology, Duke University Medical Center, Durham, NC 27710;

The current dopamine (DA) hypothesis of schizophrenia postulates striatal hyperdopaminergia and cortical hypodopaminergia. Although partial agonists at DA D2 receptors (D2Rs), like aripiprazole, were developed to simultaneously target both phenomena, they do not effectively improve cortical dysfunction. In this study, we investigate the potential for newly developed β-arrestin2 (βarr2)-biased D2R partial agonists to simultaneously target hyper- and hypodopaminergia. Read More

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http://dx.doi.org/10.1073/pnas.1614347113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167191PMC
December 2016
77 Reads
9.810 Impact Factor