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https://www.readbyqxmd.com/read/28443458/magnetic-resonance-imaging-as-a-noninvasive-method-for-longitudinal-monitoring-of-infusion-site-reactions-following-administration-of-a-novel-apomorphine-formulation
#1
Ronit Shaltiel-Karyo, Yonit Tsarfati, Anna Rubinski, Eduardo Zawoznik, Irena Weinstock, Mara Nemas, Yael S Schiffenbauer, Yuval Ramot, Abraham Nyska, Oron Yacoby-Zeevi
Infusion site reactions are common following subcutaneous infusion of drugs. Such reactions can lead to discontinuation of the treatment. Therefore, assessment of such reactions is essential during preclinical safety studies, and magnetic resonance imaging (MRI) can assist in evaluation. Here, in vivo and ex vivo MRI evaluations were used in addition to classical histopathology to assess the infusion site reaction to ND0701, a novel formulation of apomorphine base developed for the treatment of Parkinson's disease, in comparison to the commercial apomorphine hydrochloride (HCl) formulation...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28436077/neuroprotective-effect-of-epidermal-growth-factor-in-experimental-acrylamide-neuropathy-an-electrophysiological-approach
#2
H Perez-Saad, N Subiros, J Berlanga, L Aldana, D Garcia Del Barco
The neuroprotective effect of epidermal growth factor (EGF) has been documented in different contexts, but its potential benefits in peripheral neuropathies have been little studied. We investigated the neuroprotective action of EGF in experimental neuropathy induced by acrylamide (ACR). Mice and rats were treated chronically with acrylamide for 6 and 8 weeks, respectively. Concurrently they received EGF in daily doses of 1 and 5 mg/kg in mice and 3 mg/kg in rats, or saline (PBS). ACR severely affected the neurological score, the muscle strength, and the muscle potential M, in mice, as well as F-waves, sensory potentials (SP), and apomorphine-induced penile erection, in rats...
April 24, 2017: Journal of the Peripheral Nervous System: JPNS
https://www.readbyqxmd.com/read/28408348/design-and-in-vivo-evaluation-of-solid-lipid-nanoparticulate-systems-of-olanzapine-for-acute-phase-schizophrenia-treatment-investigations-on-antipsychotic-potential-and-adverse-effects
#3
Emil Joseph, Satish Reddi, Vibhu Rinwa, Garima Balwani, Ranendra Saha
The present paper discusses the design, characterization and in vivo evaluation of glyceryl monostearate nanoparticles of Olanzapine, an atypical antipsychotic drug for acute schizophrenia treatment, during which hospitalization is mandatory and adverse effects are at its peak. The solid lipid nanoparticulate system was obtained by emulsification-ultra sonication technique wherein three factors such as solid lipid content, concentration of surfactant and drug: solid lipid ratio were selected at three different levels in order to study their influence on significant characteristic responses such as particle size, encapsulation efficiency and drug content...
April 10, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28401906/acrolein-acts-as-a-neurotoxin-in-the-nigrostriatal-dopaminergic-system-of-rat-involvement-of-%C3%AE-synuclein-aggregation-and-programmed-cell-death
#4
Yi-Ting Wang, Hui-Ching Lin, Wei-Zhong Zhao, Hui-Ju Huang, Yu-Li Lo, Hsiang-Tsui Wang, Anya Maan-Yuh Lin
Clinical studies report significant increases in acrolein (an α,β-unsaturated aldehyde) in the substantia nigra (SN) of patients with Parkinson's disease (PD). In the present study, acrolein-induced neurotoxicity in the nigrostriatal dopaminergic system was investigated by local infusion of acrolein (15, 50, 150 nmoles/0.5 μl) in the SN of Sprague-Dawley rats. Acrolein-induced neurodegeneration of nigrostriatal dopaminergic system was delineated by reductions in tyrosine hydroxylase (TH) levels, dopamine transporter levels and TH-positive neurons in the infused SN as well as in striatal dopamine content...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28400230/investigation-of-the-inhibitory-mechanism-of-apomorphine-against-mdm2-p53-interaction
#5
Hiroyuki Ishiba, Taro Noguchi, Keitou Shu, Hiroaki Ohno, Kaori Honda, Yasumitsu Kondoh, Hiroyuki Osada, Nobutaka Fujii, Shinya Oishi
Mirror-image screening using d-proteins is a powerful approach to provide mirror-image structures of chiral natural products for drug screening. During the course of our screening study for novel MDM2-p53 interaction inhibitors, we identified that NPD6878 (R-(-)-apomorphine) inhibited both the native l-MDM2-l-p53 interaction and the mirror-image d-MDM2-d-p53 interaction at equipotent doses. In addition, both enantiomers of apomorphine showed potent inhibitory activity against the native MDM2-p53 interaction...
March 29, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28392213/the-acquisition-extinction-and-spontaneous-recovery-of-pavlovian-drug-conditioning-induced-by-post-trial-dopaminergic-stimulation-inhibition
#6
Breno Garone Santos, Robert J Carey, Marinete Pinheiro Carrera
In contextual drug conditioning, the onset of the drug treatment is contiguous with the contextual cues. Evidence suggests that drug conditioning also can occur if there is a discontinuity between the onset of the drug effect and offset of the contextual cues. Here we examine whether post-trial contextual drug conditioning conforms to several Pavlovian conditioning tenets namely: acquisition, extinction and spontaneous recovery. Six groups of rats received apomorphine (0.05 or 2.0mg/kg) and vehicle immediately or after a 15min delay following a 5min non-drug exposure to an open-field during three successive days (conditioning phase)...
April 7, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28390876/time-course-study-of-fractional-anisotropy-in-the-substantia-nigra-of-a-parkinsonian-rat-model-induced-by-6-ohda
#7
Wenzhong Zhang, Li Zhang, Limin Liu, Xiaomin Wang
Diffusion tensor imaging (DTI) is a non-invasive magnetic resonance imaging technique that can be used to assess microstructural changes in a brain disease such as Parkinson's disease (PD). Fractional anisotropy (FA) is a commonly used parameter in DTI analysis, although properties of DTI/FA in analyzing brain modifications in PD have been poorly profiled. This study was thus designed to characterize the detailed time course of FA in the substantia nigra (SN). A rat model of PD was induced by microinfusion of 6-OHDA into the right medial forebrain bundle...
April 5, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28382543/the-role-of-beta-arrestin2-in-shaping-fmri-bold-responses-to-dopaminergic-stimulation
#8
Kristoffer Sahlholm, Giovanna D Ielacqua, Jinbin Xu, Lynne A Jones, Felix Schlegel, Robert H Mach, Markus Rudin, Aileen Schroeter
RATIONALE: The dopamine D2 receptor (D2R) couples to inhibitory Gi/o proteins and is targeted by antipsychotic and antiparkinsonian drugs. Beta-arrestin2 binds to the intracellular regions of the agonist-occupied D2R to terminate G protein activation and promote internalization, but also to initiate downstream signaling cascades which have been implicated in psychosis. Functional magnetic resonance imaging (fMRI) has proven valuable for measuring dopamine receptor-mediated changes in neuronal activity, and might enable beta-arrestin2 function to be studied in vivo...
April 5, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28376400/antipsychotic-activity-of-embelin-isolated-from-embelia-ribes-a-preliminary-study
#9
Sharanbasappa Durg, Naveen Kumar B, Ravichandra Vandal, Shivsharan B Dhadde, B S Thippeswamy, Veeresh P Veerapur, Shrishailappa Badami
BACKGROUND: Embelia ribes is claimed in Indian traditional medical practice to be useful in the treatment of nervous diseases. Embelin, an alkyl substituted hydroxy benzoquinone, is a major active constituent of E. ribes. The present preliminary study was intended to evaluate antipsychotic activity of embelin against apomorphine-induced climbing behaviour in mice and stereotyped behaviour in rats. METHODS: Two doses of embelin (5 and 10mg/kg) were administered once daily for 15days before exposure to apomorphine...
April 1, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28364292/continuous-subcutaneous-apomorphine-infusion-in-advanced-parkinson-s-disease-10-year-experience-with-230-patients
#10
Ángel Sesar, Gustavo Fernández-Pajarín, Begoña Ares, María Teresa Rivas, Alfonso Castro
Continuous apomorphine infusion (APO) is one of the treatments available for advanced Parkinson disease (PD). Over 10 years, we have treated 230 patients with APO. Mean age was 66.8 and average evolution time at APO onset was 13.0 years. Mean duration of the treatment was 26.3 months. As of June 2016, 93 remained on the medication (active group), while 137 had stopped. This active group had mean age 67.3 at recruitment and mean evolution 14.2 years. The main indication for APO was lack of deep brain stimulation criteria (DBS)...
March 31, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28294334/comparative-assessment-of-6-18-f-fluoro-l-m-tyrosine-and-6-18-f-fluoro-l-dopa-to-evaluate-dopaminergic-presynaptic-integrity-in-a-parkinson-s-disease-rat-model
#11
REVIEW
Guillaume Becker, Bahri Mohamed Ali, Anne Michel, Fabian Hustadt, Gaëtan Garraux, André Luxen, Christian Lemaire, Alain Plenevaux
Because of the progressive loss of nigro-striatal dopaminergic terminals in Parkinson's disease (PD), in vivo quantitative imaging of dopamine (DA) containing neurons in animal models of PD is of critical importance in the pre-clinical evaluation of highly awaited disease-modifying therapies. Among existing methods, the high sensitivity of positron emission tomography (PET) is attractive to achieve that goal. The aim of this study was to perform a quantitative comparison of brain images obtained in 6-hydroxydopamine (6-OHDA) lesioned rats using two dopaminergic PET radiotracers, namely [(18) F]fluoro-3,4-dihydroxyphenyl-L-alanine ([(18) F]FDOPA) and 6-[(18) F]fluoro-L-m-tyrosine ([(18) F]FMT)...
March 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28285345/on-the-role-of-dt-diaphorase-inhibition-in-aminochrome-induced-neurotoxicity-in-vivo
#12
Andrea Herrera-Soto, Gabriela Díaz-Veliz, Sergio Mora, Patricia Muñoz, Pablo Henny, Harry W M Steinbusch, Juan Segura-Aguilar
Dopamine oxidation in the pathway leading to neuromelanin formation generates the ortho-quinone aminochrome, which is potentially neurotoxic but normally rapidly converted by DT-diaphorase to nontoxic leukoaminochrome. However, when administered exogenously into rat striatum, aminochrome is able to produce damage to dopaminergic neurons. Because of a recent report that substantia nigra pars compacta (SNpc) tyrosine hydroxylase (T-OH) levels were unaltered by aminochrome when there was cell shrinkage of dopaminergic neurons along with a reduction in striatal dopamine release, the following study was conducted to more accurately determine the role of DT-diaphorase in aminochrome neurotoxicity...
March 11, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28284752/troxerutin-exerts-neuroprotection-in-6-hydroxydopamine-lesion-rat-model-of-parkinson-s-disease-possible-involvement-of-pi3k-er%C3%AE-signaling
#13
Tourandokht Baluchnejadmojarad, Nida Jamali-Raeufy, Sedigheh Zabihnejad, Nafiseh Rabiee, Mehrdad Roghani
Parkinson's disease (PD) is a neurodegenerative disease with progressive loss of mesencephalic dopaminergic neurons of the substantia nigra and with multiple incapacitating motor and non-motor symptoms. Troxerutin is a natural bioflavonoid with nephro- and hepato-protective, antioxidant, and anti-inflammatory properties. In this study, we evaluated its possible neuroprotective effect in 6-hydroxydopamine (6-OHDA) rat model of PD. Intrastriatal 6-OHDA-lesioned rats were pretreated with troxerutin at a dose of 150mg/kg/day for 1 week...
April 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28279509/-medical-and-surgical-treatment-of-parkinson-s-disease
#14
REVIEW
Luc Defebvre, Caroline Moreau
The treatment of Parkinson's disease is symptomatic with the use of dopaminergic medications: levodopa, dopaminergic agonists and enzymatic inhibitors. At the initial stage, the main goals are to improve the quality of life of patients and delay the onset of motor complications, using a combination of these therapies taking into account both clinical disability and tolerance of different treatments. At the stage of motor and non-motor fluctuations inhibitors of MAO-B and COMT are proposed; amantadine may limit moderate dyskinesias...
March 2017: La Presse Médicale
https://www.readbyqxmd.com/read/28273839/parkinson-s-disease-from-pathogenesis-to-pharmacogenomics
#15
REVIEW
Ramón Cacabelos
Parkinson's disease (PD) is the second most important age-related neurodegenerative disorder in developed societies, after Alzheimer's disease, with a prevalence ranging from 41 per 100,000 in the fourth decade of life to over 1900 per 100,000 in people over 80 years of age. As a movement disorder, the PD phenotype is characterized by rigidity, resting tremor, and bradykinesia. Parkinson's disease -related neurodegeneration is likely to occur several decades before the onset of the motor symptoms. Potential risk factors include environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular damage, and genomic defects...
March 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28267151/regulation-of-striatal-dopamine-responsiveness-by-notch-rbp-j-signaling
#16
M Toritsuka, S Kimoto, K Muraki, M Kitagawa, T Kishimoto, A Sawa, K Tanigaki
Dopamine signaling is essential for reward learning and fear-related learning, and thought to be involved in neuropsychiatric diseases. However, the molecular mechanisms underlying the regulation of dopamine responsiveness is unclear. Here we show the critical roles of Notch/RBP-J signaling in the regulation of dopamine responsiveness in the striatum. Notch/RBP-J signaling regulates various neural cell fate specification, and neuronal functions in the adult central nervous system. Conditional deletion of RBP-J specifically in neuronal cells causes enhanced response to apomorphine, a non-selective dopamine agonist, and SKF38393, a D1 agonist, and impaired dopamine-dependent instrumental avoidance learning, which is corrected by SCH23390, a D1 antagonist...
March 7, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28266899/the-blue-lotus-flower-nymphea-caerulea-resin-used-in-a-new-type-of-electronic-cigarette-the-re-buildable-dripping-atomizer
#17
Justin L Poklis, Haley A Mulder, Matthew S Halquist, Carl E Wolf, Alphonse Poklis, Michelle R Peace
The blue lotus flower (Nymphea caerulea) is an Egyptian water lily containing apomorphine and nuciferine. Apomorphine has been described as a psychoactive alkaloid and is a non-selective dopamine agonist primarily used to treat Parkinson's disease as it stimulates dopamine receptors and improves motor function. Nuciferine is an alkaloid associated with dopamine receptor blockade. Today, blue lotus flower is used as a sleep aid and anxiety reliever. The rebuildable dripping atomizer (RDA) is an electronic cigarette that allows direct application of an e-liquid onto the coil in the atomizer for aerosolization, compared to a typical electronic cigarette where the e-liquid is wicked from a storage vessel to the coil...
March 7, 2017: Journal of Psychoactive Drugs
https://www.readbyqxmd.com/read/28239615/apomorphine-subcutaneous-injection-for-the-management-of-morning-akinesia-in-parkinson-s-disease
#18
Stuart Isaacson, Mark Lew, William Ondo, Jean Hubble, Thomas Clinch, Fernando Pagan
BACKGROUND: In patients with motor fluctuations complicating Parkinson's disease (PD), delays in time-to-ON with levodopa are common. This open-label study aimed to assess the effect of apomorphine on time-to-ON in PD patients with morning akinesia. METHODS: The safety population included 127 enrolled patients, and the full analysis set (FAS) included 88 patients. Patients completed a 7-day levodopa baseline period recording their time-to-ON following each morning dose of levodopa...
January 2017: Movement Disorders Clinical Practice
https://www.readbyqxmd.com/read/28238669/ellagic-acid-exerts-protective-effect-in-intrastriatal-6-hydroxydopamine-rat-model-of-parkinson-s-disease-possible-involvement-of-er%C3%AE-nrf2-ho-1-signaling
#19
Tourandokht Baluchnejadmojarad, Nafiseh Rabiee, Sedigheh Zabihnejad, Mehrdad Roghani
Parkinson's disease (PD) is a prevalent movement disorder in the elderly with progressive loss of mesencephalic dopaminergic neurons and incapacitating motor and non-motor complications. Ellagic acid is a natural phenolic compound with potent antioxidant and anti-inflammatory properties. In this study, we investigated its possible neuroprotective effect in 6-hydroxydopamine (6-OHDA) rat model of PD. Intrastriatal 6-OHDA-lesioned rats were pretreated with ellagic acid at a dose of 50mg/kg/day for 1week. Results showed that ellagic acid attenuates apomorphine-induced rotational bias and lowers the latency to initiate and the total time in the narrow beam task and this beneficial effect was partially abrogated following intracerebroventricular microinjection of estrogen receptor β (ERβ) antagonist...
May 1, 2017: Brain Research
https://www.readbyqxmd.com/read/28229642/sleep-loss-and-recovery-after-administration-of-drugs-related-to-different-arousal-systems-in-rats
#20
T Hajnik, A Tóth, Ö Szalontai, M Pethő, L Détári
Sleep is homeostatically regulated suggesting a restorative function. Sleep deprivation is compensated by an increase in length and intensity of sleep. In this study, suppression of sleep was induced pharmacologically by drugs related to different arousal systems. All drugs caused non-rapid eye movement (NREM) sleep loss followed by different compensatory processes. Apomorphine caused a strong suppression of sleep followed by an intense recovery. In the case of fluoxetine and eserine, recovery of NREM sleep was completed by the end of the light phase due to the biphasic pattern demonstrated for these drugs first in the present experiments...
September 2016: Physiology International
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