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https://www.readbyqxmd.com/read/28620913/efficacy-of-oral-lipid-based-formulations-of-apomorphine-and-its-diester-in-a-parkinson-s-disease-rat-model
#1
Nrupa Borkar, Daniel R Andersson, Mingshi Yang, Anette Müllertz, René Holm, Huiling Mu
OBJECTIVES: Apomorphine is used to symptomatically treat Parkinson's disease (PD). Oral delivery of apomorphine is generally limited by its short plasma half-life and a hepatic first-pass metabolism. This study was aimed at evaluating the behavioural response of apomorphine and its prodrug administered in oral lipid-based formulations. METHODS: The behavioural response of apomorphine and its prodrug administered in oral lipid-based formulations was evaluated using a 6-hydroxydopamine-lesioned rat model simulating PD symptomatology...
June 16, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28584355/perioperative-sublingual-levodopa-in-parkisnon-s-disease-a-useful-alternative
#2
Pritee H Bhirud, Jalpa Arvind Kate
Timely administration of dopamine agonists is of the essence in Parkinson's disease. The perioperative period especially for abdominal surgeries under general anaesthesia poses a challenge to oral drug administration. Alternatives such as rotigotine patches and subcutaneous apomorphine administration have been described but unavailability restricts their use. Sublingual administration of tablet levodopamine as an alternative worked well in our patients and we would like to describe the same.
May 2017: Indian Journal of Anaesthesia
https://www.readbyqxmd.com/read/28577498/telomerase-reverse-transcriptase-genetically-modified-adipose-tissue-derived-stem-cells-improves-erectile-dysfunction-by-inhibiting-oxidative-stress-and-enhancing-proliferation-in-rat-model
#3
Xiao-Jun Wu, Wen-Hao Shen, Peng He, Xiao-Zhou Zhou, Yi Zhi, Qiang Dai, Zhi-Wen Chen, Zhan-Song Zhou
Erectile dysfunction (ED) is considered to be incapable of obtaining or/and keeping a sufficient erection function to receive the satisfactory during the sexual intercourse. This study aims to investigate the effects of telomerase reverse transcriptase (hTERT) modified adipose tissue derived stem cells (ADSCs) autologously injected into cavernosa of the ED rats on erectile function. The ADSCs were isolated form the rat subcutaneous adipose tissue sample, and identified by examining the CD29 and CD44 molecule...
May 31, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28554418/device-aided-treatment-strategies-in-advanced-parkinson-s-disease
#4
Jonathan Timpka, Bianca Nitu, Veronika Datieva, Per Odin, Angelo Antonini
With peroral levodopa treatment, a majority of patients develop motor fluctuations and dyskinesia already within a few years of therapy. Device-aided Parkinson (PD) therapies refer to deep brain stimulation (DBS), levodopa-carbidopa intestinal gel infusion (LCIG), and subcutaneous infusion of the dopamine agonist apomorphine and represent effective strategies counteracting motor fluctuations and dyskinesia. These three therapy options seem to be similarly effective in reducing "time with PD symptoms (off time)" by at least 60%-65%...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28554412/hallmarks-of-treatment-aspects-parkinson-s-disease-throughout-centuries-including-l-dopa
#5
Hee J Kim, Beom S Jeon, Peter Jenner
Deficit of striatal dopamine was first discovered in postmortem brain of patients with Parkinson's disease in 1960. This observation was the starting point for dopamine replacement therapy, and successful introduction of high dose l-dopa therapy in the 1969 revolutionized the treatment of Parkinson's disease. Since then, constant attempts have been made to enhance the efficacy of l-dopa and reduce motor complications by providing more continuous dopamine stimulation. This chapter traces the hallmarks of medical treatments for Parkinson's disease throughout centuries including the first description of antiparkinsonian effects of anticholinergics, the birth of apomorphine in the 1900s, then discovery of l-dopa in the 1960s, and development of dopamine agonists since the 1970s...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28550249/avn-492-a-novel-highly-selective-5-ht6r-antagonist-preclinical-evaluation
#6
Alexandre V Ivachtchenko, Ilya Okun, Vladimir Aladinskiy, Yan Ivanenkov, Angela Koryakova, Ruben Karapetyan, Oleg Mitkin, Ramiz Salimov, Andrey Ivashchenko
Discovery of 5-HT6 receptor subtype and its exclusive localization within the central nervous system led to extensive investigations of its role in Alzheimer's disease, schizophrenia, and obesity. In the present study, we present preclinical evaluation of a novel highly-potent and highly-selective 5-HT6R antagonist, AVN-492. The affinity of AVN-492 to bind to 5-HT6R (Ki = 91 pM) was more than three orders of magnitude higher than that to bind to the only other target, 5-HT2BR, (Ki = 170 nM). Thus, the compound displayed great 5-HT6R selectivity against all other serotonin receptor subtypes, and is extremely specific against any other receptors such as adrenergic, GABAergic, dopaminergic, histaminergic, etc...
May 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28550243/apomorphine-therapy-for-neuronal-insulin-resistance-in-a-mouse-model-of-alzheimer-s-disease
#7
Norimichi Nakamura, Yasumasa Ohyagi, Tomohiro Imamura, Yuki T Yanagihara, Kyoko M Iinuma, Naoko Soejima, Hiroyuki Murai, Ryo Yamasaki, Jun-Ichi Kira
Apomorphine (APO) promotes intraneuronal amyloid-β (Aβ) degradation and improves memory function in an Alzheimer's disease (AD) model, 3xTg-AD mice. Since insulin resistance is increased in AD neurons, we investigated the effects of APO on brain insulin resistance in 3xTg-AD mice at early and late stages. After 1-month subcutaneous injection of Apokyn® to 3xTg-AD mice at 6 or 12 months of age, memory function was significantly improved in both age groups. Protein levels of insulin-degrading enzyme (IDE), which is linked to insulin signaling and degrades Aβ, significantly increased in the 3xTg-AD mice brain compared with non-transgenic mice, and were further increased by APO...
May 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28493825/repetitive-transcranial-magnetic-stimulation-for-treatment-of-lactacystin-induced-parkinsonian-rat-model
#8
Maowen Ba, Guozhao Ma, Chao Ren, Xuwen Sun, Min Kong
The dysfunction of ubiquitin-proteasome system is an important pathogenesis in the neurodegenerative process of Parkinson's disease. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive and potential method in treating Parkinson's disease. To investigate whether rTMS has neuroprotective effects in parkinsonian rat model induced by ubiquitin-proteasome system impairment, we gave rTMS daily for 4 weeks to proteasome inhibitor, lactacystin-induced parkinsonian rat model. Rotational behavior test demonstrated that rTMS obviously reduced apomorphine-induced turning number in parkinsonian rats...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28465234/apomorphine-suppresses-tnf-%C3%AE-induced-mmp-9-expression-and-cell-invasion-through-inhibition-of-erk-ap-1-signaling-pathway-in-mcf-7-cells
#9
Yeon-Seop Jung, Syng-Ook Lee
Recent studies have shown that dopamine plays an important role in several types of cancer by inhibiting cell growth and invasion via dopamine receptors (DRs), such as dopamine receptor D2. However, the roles of DR agonists in cancer cell growth and invasion remain unclear. In our study, we found that apomorphine (APO), one of the most commonly prescribed DR agonists, inhibited TNF-α-induced matrix metalloprotease-9 (MMP-9) expression and cell invasion in MCF-7 human breast carcinoma cells through DR-independent pathways...
June 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28450692/the-ethyl-acetate-fraction-of-a-methanolic-extract-of-unripe-noni-morinda-citrifolia-linn-fruit-exhibits-a-biphasic-effect-on-the-dopaminergic-system-in-mice
#10
Vijayapandi Pandy, Megala Narasingam, Kamini Vijeepallam, Syam Mohan, Vasudevan Mani, Zahurin Mohamed
In earlier ex vivo studies, we reported the biphasic effect of a methanolic extract of unripe Morinda citrifolia fruit (MMC) on dopamine-induced contractility in isolated rat vas deferens preparations. The present in vivo study was designed and undertaken to further explore our earlier ex vivo findings. This study examined the effect of the ethyl acetate fraction of a methanolic extract of unripe Morinda citrifolia Linn. fruit (EA-MMC; 5-100 mg/kg, p.o.) on the dopaminergic system using mouse models of apomorphine-induced climbing time and climbing behavior, methamphetamine-induced stereotypy (sniffing, biting, gnawing, and licking) and haloperidol-induced catalepsy using the bar test...
April 26, 2017: Experimental Animals
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
#11
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
#12
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
#13
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 11, 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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...
June 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
#20
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
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