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https://www.readbyqxmd.com/read/29128144/the-antipsychotic-drug-brexpiprazole-reverses-phencyclidine-induced-disruptions-of-thalamocortical-networks
#1
Hanna E van den Munkhof, Jørn Arnt, Pau Celada, Francesc Artigas
Brexpiprazole (BREX), a recently approved antipsychotic drug in the US and Canada, improves cognitive dysfunction in animal models, by still largely unknown mechanisms. BREX is a partial agonist at 5-HT1A and D2 receptors and antagonist at α1B- and α2C-adrenergic and 5-HT2A receptors all with a similar potency. The NMDA receptor antagonist phencyclidine (PCP), used as pharmacological model of schizophrenia, activates thalamocortical networks and decreases low frequency oscillations (LFO; <4 Hz). These effects are reversed by antipsychotics...
November 8, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29122692/blockade-of-platelet-activating-factor-receptor-attenuates-abnormal-behaviors-induced-by-phencyclidine-in-mice-through-down-regulation-of-nf-%C3%AE%C2%BAb
#2
The-Vinh Tran, Se Jin Park, Eun-Joo Shin, Hai-Quyen Tran, Ji Hoon Jeong, Choon-Gon Jang, Yu Jeung Lee, Seung-Yeol Nah, Toshitaka Nabeshima, Hyoung-Chun Kim
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. Here, we investigated the role of PAF-R in the abnormal behaviors induced by PCP in mice. Repeated treatment with PCP resulted in a significant increase in PAF-R gene expression in the prefrontal cortex (PFC) and in the hippocampus...
November 7, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29118102/phencyclidine-discoordinates-hippocampal-network-activity-but-not-place-fields
#3
Hsin-Yi Kao, Dino Dvořák, EunHye Park, Jana Kenney, Eduard Kelemen, André A Fenton
We used the psychotomimetic phencyclidine (PCP) to investigate the relationships between cognitive behavior, coordinated neural network function and information processing within the hippocampus place cell system. We report in rats that PCP (5mg/kg i.p.) impairs a well-learned hippocampus-dependent place avoidance behavior in rats that requires cognitive control, even when PCP is injected directly into dorsal hippocampus. PCP increases 60-100 Hz medium gamma oscillations in hippocampus CA1 and these increases correlate with the cognitive impairment caused by systemic PCP administration...
November 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29082316/the-use-of-cannabis-by-patients-with-sickle-cell-disease-increased-the-frequency-of-hospitalization-due-to-vaso-occlusive-crises
#4
Samir K Ballas
Introduction: The objective of this study was to determine if patients with sickle cell disease using cannabis had decreased frequency of acute vaso-occlusive crises (VOCs) that required hospitalization. Method: This was a retrospective study in which 270 urine drug screen tests were done on 72 patients: 40 males and 32 females. Results: Cannabinoids were found in 144 urine tests from 37 patients and were negative in 126 tests from 35 patients. Males who used cannabis were significantly younger (p<0.001) than males who did not...
2017: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/29076977/multiple-actions-of-phencyclidine-and-mk-801-on-isolated-bovine-cerebral-arteries
#5
Woodrow W Wendling, Dong Chen, Karen S Wendling, Ihab R Kamel
This study examines the direct effects of 3 noncompetitive N-methyl-D-aspartate receptor antagonists, phencyclidine (PCP), (+)MK-801, and (-)MK-801, on bovine middle cerebral arteries (BMCA). Rings of BMCA were mounted in isolated tissue chambers equipped with isometric tension transducers to obtain pharmacologic dose-response curves. In the absence of endogenous vasoconstrictors, the 3 N-methyl-D-aspartate antagonists each produced direct constriction of BMCA. The thromboxane A2 receptor antagonist SQ-29,548, the TxA2 synthase inhibitor furegrelate, the calcium antagonist nimodipine, and calcium-deficient media all inhibited maximal phencyclidine or (+)MK-801-induced constriction...
October 25, 2017: Journal of Neurosurgical Anesthesiology
https://www.readbyqxmd.com/read/29068002/engineered-d2r-variants-reveal-the-balanced-and-biased-contributions-of-g-protein-and-%C3%AE-arrestin-to-dopamine-dependent-functions
#6
Samuel J Rose, Thomas F Pack, Sean M Peterson, Kaitlin Payne, Emiliana Borrelli, Marc G Caron
The dopamine D2 receptor (D2R), like many G-protein coupled-receptors, signals through G-protein and β-arrestin-dependent pathways. Preferential activation of one of these pathways is termed functional selectivity or biased signaling and is a promising therapeutic strategy. Though biased signaling through D2Rs has been demonstrated, acquiring the mechanistic details of biased D2R/G-protein and D2R/β-arrestin signaling in vivo has been challenging due to the lack of techniques that specifically target these interactions in discrete cell populations...
October 25, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29065422/acute-phencyclidine-alters-neural-oscillations-evoked-by-tones-in-the-auditory-cortex-of-rats
#7
Ashley M Schnakenberg Martin, Brian F OʼDonnell, James B Millward, Jenifer L Vohs, Emma Leishman, Amanda R Bolbecker, Olga Rass, Sandra L Morzorati
BACKGROUND/AIMS: The onset response to a single tone as measured by electroencephalography (EEG) is diminished in power and synchrony in schizophrenia. Because neural synchrony, particularly at gamma frequencies (30-80 Hz), is hypothesized to be supported by the N-methyl-D-aspartate receptor (NMDAr) system, we tested whether phencyclidine (PCP), an NMDAr antagonist, produced similar deficits to tone stimuli in rats. METHODS: Experiment 1 tested the effect of a PCP dose (1...
October 24, 2017: Neuropsychobiology
https://www.readbyqxmd.com/read/29044958/a-simple-validated-multi-method-for-detecting-drugs-in-oral-fluid-by-ultra-performance-liquid-chromatography-tandem-mass-spectrometry-uplc-ms-ms
#8
Yufang Zheng, Erik Sparve, Mats Bergström
BACKGROUND: Oral fluid sampling offers several advantages compared to other methods of detecting drugs in biological matrices due to its easy sampling procedure and simple supervision. Hence, the use of oral fluid for drug testing is increasing in workplaces and in roadside testing. As a result, more laboratories are required to perform analyses of drugs in oral fluid. METHODS: A multi-method using Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) for tracing drugs in oral fluid was developed...
October 16, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/29037473/ginsenoside-re-protects-against-phencyclidine-induced-behavioral-changes-and-mitochondrial-dysfunction-via-interactive-modulation-of-glutathione-peroxidase-1-and-nadph-oxidase-in-the-dorsolateral-cortex-of-mice
#9
The-Vinh Tran, Eun-Joo Shin, Duy-Khanh Dang, Sung Kwon Ko, Ji Hoon Jeong, Seung-Yeol Nah, Choon-Gon Jang, Yu Jeung Lee, Kazuya Toriumi, Toshitaka Nabeshima, Hyoung-Chun Kim
We investigated whether ginsenoside Re (Re) modulates phencyclidine (PCP)-induced sociability deficits and recognition memory impairments to extend our recent finding. We examined the role of GPx-1 gene in the pharmacological activity of Re against mitochondrial dysfunction induced by PCP in the dorsolateral cortex of mice. Since mitochondrial oxidative stress activates NADPH oxidase (PHOX), we applied PHOX inhibitor apocynin for evaluating interactive modulation between GPx-1 and PHOX against PCP neurotoxicity...
October 14, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29020988/haloperidol-affects-bones-while-clozapine-alters-metabolic-parameters-sex-specific-effects-in-rats-perinatally-treated-with-phencyclidine
#10
Tatjana Nikolić, Milan Petronijević, Jelena Sopta, Milica Velimirović, Tihomir Stojković, Gordana Jevtić Dožudić, Milan Aksić, Nevena V Radonjić, Nataša Petronijević
BACKGROUND: The presentation of schizophrenia (SCH) symptoms differs between the sexes. Long-term treatment with antipsychotics is frequently associated with decreased bone mineral density, increased fracture risk and metabolic side effects. Perinatal phencyclidine (PCP) administration to rodents represents an animal model of SCH. The aim of this study was to assess the effects of chronic haloperidol and clozapine treatment on bone mass, body composition, corticosterone, IL-6 and TNF-α concentrations and metabolic parameters in male and female rats perinatally treated with PCP...
October 11, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28971230/effects-of-2-bromoterguride-a-dopamine-d2-receptor-partial-agonist-on-cognitive-dysfunction-and-social-aversion-in-rats
#11
Emilia Tarland, Robert T Franke, Heidrun Fink, Heinz H Pertz, Jan Brosda
RATIONALE: 2-Bromoterguride, a dopamine D2 receptor partial agonist with antagonist properties at serotonin 5-HT2A receptors and α2C-adrenoceptors, meets the prerequisites of a putative atypical antipsychotic drug (APD). We recently showed that 2-bromoterguride is effective in tests of positive symptoms of schizophrenia in rats without inducing extrapyramidal side effects or metabolic changes. OBJECTIVE: In continuation of our recent work, we now investigated the effect of 2-bromoterguride on apomorphine and phencyclidine (PCP)-induced disruptions of prepulse inhibition (PPI) of the acoustic startle response, a measure of sensory gating...
October 3, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28946779/muscarinic-receptor-signaling-contributes-to-atypical-antipsychotic-drug-reversal-of-the-phencyclidine-induced-deficit-in-novel-object-recognition-in-rats
#12
Masanori Miyauchi, Nichole M Neugebauer, Tatsuya Sato, Hossein Ardehali, Herbert Y Meltzer
Enhancement of cholinergic function via muscarinic acetylcholine receptor M1 agonism improves cognition in some schizophrenia patients. Most atypical antipsychotic drugs, including clozapine and its active metabolite, N-desmethylclozapine, and lurasidone, enhance the release of acetylcholine in key brain regions involved in cognition (e.g. hippocampus). We determined the effect of muscarinic acetylcholine receptor M1 stimulation on novel object recognition and its contribution to the ability of atypical antipsychotic drugs to reverse the novel object recognition deficit in rats withdrawn from subchronic phencyclidine, a rodent model of cognitive impairment in schizophrenia...
September 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28936010/dextromethorphan-in-cough-syrup-the-poor-man-s-psychosis
#13
Bridgette Martinak, Ramy A Bolis, Jeffrey Ryne Black, Rachel E Fargason, Badari Birur
Dextromethorphan (3-methoxy-N-methylmorphinan), also known as "DXM" and "the poor man's PCP," is a synthetically produced drug that is available in more than 140 over-the-counter cough and cold preparations. Dextromethorphan (DXM) has overtaken codeine as the most widely used cough suppressant due to its availability, efficacy, and safety profile at directed doses. However, DXM is subject to abuse. When consumed at inappropriately high doses (over 1500 mg/day), DXM can induce a state of psychosis characterized by Phencyclidine (PCP)-like psychological symptoms, including delusions, hallucinations, and paranoia...
September 15, 2017: Psychopharmacology Bulletin
https://www.readbyqxmd.com/read/28842124/phencyclidine-induced-dysregulation-of-primary-cilia-in-the-rodent-brain
#14
Hiroki Shiwaku, Asami Umino, Masakazu Umino, Toru Nishikawa
Significant roles of the primary cilia in the central nervous system have been reported in neural generation and cognitive functions. However, little is known about the possible pathological changes in brain primary cilia in neuropsychiatric disorders. To obtain an insight into the relationship between cilial dysregulation and schizophrenia, we presently investigated the effects of psychotomimetics, phencyclidine, MK-801 (dizocilpine), and methamphetamine, on morphological and molecular indices in the rodent brain...
August 22, 2017: Brain Research
https://www.readbyqxmd.com/read/28830759/phencyclidine-like-in%C3%A2-vivo-effects-of-methoxetamine-in-mice-and-rats
#15
Michael D Berquist, William S Hyatt, Jonathan Bauer-Erickson, Brenda M Gannon, Andrew P Norwood, William E Fantegrossi
Methoxetamine (MXE) is a novel drug of abuse that is structurally similar to phencyclidine (PCP). In the present study, rats were trained to discriminate PCP from saline and substitution tests were performed with arylcyclohexylamines PCP, eticyclidine (PCE), tenocyclidine (TCP), and MXE. PCP and PCE engendered PCP-lever selection in all subjects, whereas MXE and TCP produced PCP-lever selection in animals that did not display behavioral disruption. Last, the substituted tryptamine dipropyltryptamine (DPT) produced moderate PCP-lever selection and elicited behavioral disruption in all subjects at the highest dose tested...
August 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28830118/two-fatal-intoxications-involving-3-methoxyphencyclidine
#16
Christie Mitchell-Mata, Brittany Thomas, Brianna Peterson, Fiona Couper
3- and 4-methoxyphencyclidine (3-MeO-PCP, 4-MeO-PCP), structural analogs of phencyclidine (PCP), were among the first legal PCP alternatives to show up on the novel psychoactive substances (NPS) market in Europe in the 2000s. Their structural similarities to PCP and ketamine likely contribute to their demonstrated dissociative anesthetic effects. Limited information exists in the literature about toxic and lethal concentrations of these drugs in biological samples. This case report presents the first two death cases in Washington State in which 3-MeO-PCP was identified...
July 1, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/28818421/erbb-signaling-antagonist-ameliorates-behavioral-deficit-induced-by-phencyclidine-pcp-in-mice-without-affecting-metabolic-syndrome-markers
#17
Hagar Tadmor, Idit Golani, Ravid Doron, Ilana Kremer, Alon Shamir
Schizophrenia is a severe syndrome that affects about 1% of the world population. Since the mid-1950s, antipsychotics have been used to treat schizophrenia with preference for treating positive symptoms; however, their tolerance level is low, there are numerous side effects, and only some patients respond to the treatment. Antipsychotic medications that are more effective, better tolerated, and with fewer adverse effects are urgently needed. Given the accumulating evidence of the role filled by the ErbB signaling network in the biology of the dopamine, GABA, and glutamate systems, and in the etiology of schizophrenia, we hypothesized that the ErbB network is a candidate for development of a novel agent through which various symptoms of schizophrenia and other psychiatric disorders might be treated...
August 14, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28816240/rodent-mismatch-negativity-mmn-theta-neuro-oscillatory-response-as-a-translational-neurophysiological-biomarker-for-n-methyl-d-aspartate-receptor-based-new-treatment-development-in-schizophrenia
#18
Migyung Lee, Andrea Balla, Henry Sershen, Pejman Sehatpour, Peter Lakatos, Daniel C Javitt
Deficits in the generation of auditory mismatch negativity (MMN) generation are among the most widely replicated neurophysiological abnormalities in schizophrenia and linked to underlying dysfunction of N-methyl-D-aspartate receptor (NMDAR)-mediated neurotransmission. Here, we evaluate physiological properties of rodent MMN, along with sensitivity to NMDAR agonist and antagonist treatment, relative to known patterns of dysfunction in schizophrenia. Epidural neurophysiological responses to frequency- and duration-deviants, along with responses to standard stimuli, were obtained at baseline and following 2 and 4 weeks treatment from rats treated with saline, phencyclidine (PCP, 15 mg/kg/d by osmotic minipump), or PCP+glycine (16% by weight diet) interventions...
August 17, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28801194/medial-septum-modulates-hippocampal-gamma-activity-and-prepulse-inhibition-in-an-n-methyl-d-aspartate-receptor-antagonist-model-of-schizophrenia
#19
L Stan Leung, Jingyi Ma
We reviewed the participation of the septohippocampal system in an animal model of schizophrenia that was acutely induced by systemic injection of an N-methyl-d-aspartate (NMDA) receptor antagonist such as phencyclidine, MK-801 and ketamine. The NMDA receptor antagonist-induced model of schizophrenia is characterized by behavioral and electrophysiological disruptions, including a decrease in prepulse inhibition of the acoustic startle response (PPI), hyperlocomotion, decrease in gating of hippocampal auditory evoked potentials and robust increase in hippocampal gamma (30-100Hz) oscillations...
August 8, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28774576/synthesis-and-biological-investigation-of-tetrahydropyridopyrimidinone-derivatives-as-potential-multireceptor-atypical-antipsychotics
#20
Hainimu Xiamuxi, Zhen Wang, Jianfeng Li, Yu Wang, Chunhui Wu, Feipu Yang, Xiangrui Jiang, Yongjian Liu, Qingjie Zhao, Weiming Chen, Jian Zhang, Yuanchao Xie, Tianwen Hu, Mingshuo Xu, Shuang Guo, Haji Akber Aisa, Yang He, Jingshan Shen
In the present study, a series of tetrahydropyridopyrimidinone derivatives, possessing potent dopamine D2, serotonin 5-HT1A and 5-HT2A receptors properties, was synthesized and evaluated as potential antipsychotics. Among them, 3-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one (10d) held the best pharmacological profile. It not only exhibited potent and balanced activities for D2, 5-HT1A, and 5-HT2A receptors, but was also endowed with low activities for α1A, 5-HT2C, H1 receptors and hERG channels, suggesting a low propensity for inducing orthostatic hypotension, weight gain and QT prolongation...
September 1, 2017: Bioorganic & Medicinal Chemistry
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