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D Gutiérrez-Fernández, A Moreno-Ancillo, A Foncubierta-Fernández, F Medina-Varo, J A Andrés-García, M J Fernández-Anguita
No abstract text is available yet for this article.
October 2016: Journal of Investigational Allergology & Clinical Immunology
Zen Yang Ang, Michael Boddy, Yandi Liu, Bruce Sunderland
Apomorphine in solution undergoes rapid autoxidation, producing greenish colored solutions, making it difficult to formulate as a stable pharmaceutical solution. To identify the optimum antioxidant agent/combination for apomorphine solution, a high performance liquid chromatography assay was used to study the stability of 50 μg/mL apomorphine HCI in 0.1% L-ascorbic acid (AA), 0.1% sodium metabisulfite (SMB), 0.1% EDTA, and in selected combinations at 25°C, 32°C, and 37°C over a period of 14 days. The stability of apomorphine HCl (10 mg/mL) in 0...
2016: Drug Design, Development and Therapy
Andresa H Betti, Camila B Antonio, Thais E T Pompeu, Thaise S Martins, Vivian Herzfeldt, Eveline D Stolz, Carlos A M Fraga, Eliezer Barreiro, François Noël, Stela M K Rates
Aiming to identify new antipsychotic lead-compounds, our group has been working on the design and synthesis of new N-phenylpiperazine derivatives. Here, we characterized LASSBio-1422 as a pharmacological prototype of this chemical series. Adult male Wistar rats and CF1 mice were used for in-vitro and in-vivo assays, respectively. LASSBio-1422 [1 and 5 mg/kg, postoperatively (p.o.)] inhibited apomorphine-induced climbing as well as ketamine-induced hyperlocomotion (1 and 5 mg/kg, p.o.), animal models predictive of efficacy on positive symptoms...
October 13, 2016: Behavioural Pharmacology
Alireza Sarkaki, Yaghoob Farbood, Mojtaba Dolatshahi, Seyed Mohammad Taqhi Mansouri, Ali Khodadadi
Antioxidants have protective effects against free radicals-induced neural damage in Parkinson's disease (PD). We examined the effects of ellagic acid (EA) on locomotion, pallidal local EEG, and its frequency bands' power and also cerebral antioxidant contents in a rat model of PD induced by 6-hydroxidopamine (6-OHDA). 6-OHDA (16 µg/2µ l) was injected into the right medial forebrain bundle (MFB) in MFB-lesioned rat's brain. Sham group received vehicle instead of 6-OHDA. PD-model was confirmed by rotational test using apomorphine injection...
August 2016: Acta Medica Iranica
Na Hyea Kang, Candace H Carriere, Sarra G Bahna, Lennard P Niles
The indoleamine hormone melatonin protects dopamine neurons in the rat nigrostriatal pathway following 6-hydroxydopamine lesioning, and an increase in striatal melatonin levels has been detected in this model of Parkinson's disease. Melatonin induces the expression of tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, in the ventral midbrain, where G protein-coupled melatonin receptors are present. Based on the interaction between the melatonergic and dopaminergic systems, we hypothesized that 6-hydroxydopamine-induced degeneration of dopamine neurons would affect the expression of melatonin receptors in the nigrostriatal pathway...
September 27, 2016: Brain Research
Martijn M Selten, Francisca Meyer, Wei Ba, Astrid Vallès, Dorien A Maas, Moritz Negwer, Vivian D Eijsink, Ruben W M van Vugt, Josephus A van Hulten, Nick H M van Bakel, Joey Roosen, Robert J van der Linden, Dirk Schubert, Michel M M Verheij, Nael Nadif Kasri, Gerard J M Martens
Schizophrenia is a complex disorder that affects cognitive function and has been linked, both in patients and animal models, to dysfunction of the GABAergic system. However, the pathophysiological consequences of this dysfunction are not well understood. Here, we examined the GABAergic system in an animal model displaying schizophrenia-relevant features, the apomorphine-susceptible (APO-SUS) rat and its phenotypic counterpart, the apomorphine-unsusceptible (APO-UNSUS) rat at postnatal day 20-22. We found changes in the expression of the GABA-synthesizing enzyme GAD67 specifically in the prelimbic- but not the infralimbic region of the medial prefrontal cortex (mPFC), indicative of reduced inhibitory function in this region in APO-SUS rats...
September 30, 2016: Scientific Reports
Gustavo Fernández-Pajarín, Ángel Sesar, Begoña Ares, Alfonso Castro
BACKGROUND: There are not many data about the beneficial effect of nocturnal continuous subcutaneous apomorphine infusion (NCSAI) over sleep disturbances in advanced Parkinson's disease (PD). OBJECTIVE: Evaluate the effect of the NCSAI in sleeping problems and insomnia due to nocturnal hypokinesia inadvanced PD. METHODS: We assessed 17 advanced PD patients with several sleep disturbances measured by SCOPA-SLEEP and PDSS scales. All the patients were on apomorphine infusion during daytime...
September 20, 2016: Journal of Parkinson's Disease
Majid Jadidi, Saeed Moghadas Biat, Hamid Reza Sameni, Manouchehr Safari, Abbas Ali Vafaei, Laya Ghahari
OBJECTIVES: The main characteristic of mesenchymal stem cells (MSCs) is their ability to produce other cell types. Electromagnetic field (EMF) stimulates differentiation of MSCs into other cells. In this study, we investigated whether EMF can effect on the differentiation of MSCs into dopaminergic (DA) neurons. MATERIALS AND METHODS: An EMF with a frequency of 50 Hz and two intensities of 40 and 400 µT 1hr/day was generated around the cells for a week. Afterwards, these cells were injected into the left ventricle of Parkinsonian rats...
July 2016: Iranian Journal of Basic Medical Sciences
John A Rudd, Man P Ngan, Zengbing Lu, Guy A Higgins, Claudio Giuliano, Emanuela Lovati, Claudio Pietra
BACKGROUND AND AIMS: Chemotherapy-induced acute and delayed emesis involves the activation of multiple pathways, with 5-hydroxytryptamine (5-HT; serotonin) playing a major role in the initial response. Substance P tachykinin NK1 receptor antagonists can reduce emesis induced by disparate emetic challenges and therefore have a clinical utility as broad inhibitory anti-emetic drugs. In the present studies, we investigate the broad inhibitory anti-emetic profile of a relatively new NK1 receptor antagonist, netupitant, alone or in combination with the long acting 5-HT3 receptor antagonist, palonosetron, for a potential to reduce emesis in ferrets and shrews...
2016: Frontiers in Pharmacology
Giovanni Hernandez, Marie-Pierre Cossette, Peter Shizgal, Pierre-Paul Rompré
Glutamate stimulates ventral midbrain (VM) N-Methyl-D-Aspartate receptors (NMDAR) to initiate dopamine (DA) burst firing activity, a mode of discharge associated with enhanced DA release and reward. Blockade of VM NMDAR, however, enhances brain stimulation reward (BSR), the results can be explained by a reduction in the inhibitory drive on DA neurons that is also under the control of glutamate. In this study, we used fast-scan cyclic voltammetry (FSCV) in anesthetized animals to determine whether this enhancement is associated with a change in phasic DA release in the nucleus accumbens...
2016: Frontiers in Behavioral Neuroscience
Kesinee Netsomboon, Alexandra Partenhauser, Julia Rohrer, Nadine Elli Sündermann, Felix Prüfert, Wongsakorn Suchaoin, Flavia Laffleur, Andreas Bernkop-Schnürch
The purpose of this study was to synthesize preactivated thiomers with different degree of preactivation and to evaluate their potential as novel excipient for nasal apomorphine administration. The thiomer (PAA-cys) was synthesized by addition of thiol groups on poly(acrylic acid) with various molecular mass including 100, 250 and 450 kDa followed by immobilization of 2-mercaptonicotinic acid (2MNA) to thiol groups by disulfide bond formation resulting in PAA-cys-2MNA. These thiomers (PAA100-cys, PAA250-cys and PAA450-cys) were in the next step preactivated by 56...
September 8, 2016: European Journal of Pharmaceutics and Biopharmaceutics
Nrupa Borkar, René Holm, Mingshi Yang, Anette Müllertz, Huiling Mu
In the present study, the differences in oral absorption of apomorphine and its diester prodrugs and the effect of lipid-based formulations on the absorption of apomorphine or its prodrugs were investigated. Apomorphine, dilauroyl apomorphine (DLA) and dipalmitoyl apomorphine (DPA) were orally administered (0.24mmol/kg) to rats as: DLA-o/w emulsion, DPA-o/w emulsion, apomorphine-o/w emulsion, apomorphine aqueous suspension, DLA-Maisine, DLA-soybean oil, DLA-self-emulsifying drug delivery systems (SEDDS), and DLA-w/o emulsion...
September 9, 2016: International Journal of Pharmaceutics
Maryam Rezaei, Sima Nasri, Mehrdad Roughani, Zeinab Niknami, Seyed Ali Ziai
Parkinson's disease is one of the most common neurodegenerative disorders. There are many documents about the effects of oxidative stress in Parkinson's disease etiology. Angiotensin II activates NADPH dependent oxidases and causes superoxides formation. Peganum harmala L. extract, which has angiotensin converting enzyme (ACE) inhibitory effect, is considered to evaluate oxidative stress inhibition and Parkinson's disease improvement. Male rats weighting 200-250 g were divided into 5 groups: Control, Neurotoxin (injection of 6-hydroxydopamine into left hemisphere substantia nigra), Peganum harmala's seeds aqueous extract (10 mg/kg) and captopril (5 mg/kg)...
2016: Iranian Journal of Pharmaceutical Research: IJPR
Robert Drozd, Przemyslaw E Cieslak, Michal Rychlik, Jan Rodriguez Parkitna, Rafal Rygula
Although the cognitive theory has implicated judgment bias in various psychopathologies, its role in decision making under risk remains relatively unexplored. In the present study, we assessed the effects of cognitive judgment bias on risky choices in rats. First, we trained and tested the animals on the rat version of the probability-discounting (PD) task. During discrete trials, the rats chose between two levers; a press on the "small/certain" lever always resulted in the delivery of one reward pellet, whereas a press on the "large/risky" lever resulted in the delivery of four pellets...
2016: Frontiers in Behavioral Neuroscience
Masahide Fukada, Atsuo Nakayama, Takayoshi Mamiya, Tso-Pang Yao, Yoshiharu Kawaguchi
Histone deacetylase 6 (Hdac6), a multifunctional cytoplasmic deacetylase, is abundant in brain. We previously demonstrated that global Hdac6 depletion causes aberrant emotional behaviors in mice. Identification of affected brain systems and its molecular basis will lead to new insights into relations between protein acetylation events and psychiatric disorders. Here we report the dopaminergic abnormalities in Hdac6 KO mice. The dopamine transmission mediated by D1-like and D2-like G protein-coupled dopamine receptors is known to play roles in controlling movement, cognition, and motivational processes, and its dysfunction causes psychiatric disorders...
November 2016: Neuropharmacology
Abbas Aliaghaei, Mossa Gardaneh, Nader Maghsoudi, Parvin Salehinejad, Ehsan Gharib
BACKGROUND/OBJECTIVE: Degeneration of dopaminergic neurons in Parkinson's disease (PD) implies cell replacement using potentially differentiable sources as a promising therapeutic solution. We tested the capacity of conditioned medium from choroid plexus epithelial cells (CPECs-CM) to induce the dopaminergic potential of umbilical cord matrix mesenchymal stem cells (UCMSCs). METHODS: We isolated UCMSCs from human umbilical cord and CPECs from rat brain. Following expansion and characterization, CPECs-CM were collected, tested for expression of various growth factors, and applied to UCMSCs...
August 2016: Archives of Iranian Medicine
Hong-Shun Gu, Xi Chen, Jian-Wei Zhang, Lan Zhang, Lin Li
In the present study, a series of novel flavanone derivatives were designed and synthesized, and the antipsychotic activities of the target compounds were evaluated in vitro and in vivo. The results showed that synthesized compounds 7a-7g decreased the activity of dopamine D2 receptors in HEK293 cells co-transfected with D2 receptor/G protein α16a, with IC50 values of 0.051-0.35 μM. Compounds 7a-7g inhibited the over-production of nitric oxide stimulated by lipopolysaccharide/interferon-γ in BV-2 microglial cells...
August 20, 2016: Chemical Biology & Drug Design
Ulf Simonsen, Simon Comerma-Steffensen, Karl-Erik Andersson
The currently recommended first-line treatments of erectile dysfunction, phosphodiesterase type 5 inhibitors (PDE5i), e.g. sildenafil, are efficacious in many patients with erectile dysfunction of vascular origin, but this therapy is insufficient in approximately 30-40% of men with erectile dysfunction where there is also a neuronal affection. There is a demand of novel approaches to treat the condition. We review the possibility of modulating the dopaminergic pathways to improve erectile function. Dopamine D1 (D1 , D5 )-and D2 (D2 -D4 )-like receptors in the paraventricular area, the medial preoptic area, the spinal cord, and in the erectile tissue are involved in erection, and several agonists developed for treatment of Parkinson's disease are associated with increased libido...
August 19, 2016: Basic & Clinical Pharmacology & Toxicology
R K Mo, J Wang, J Y Huang, Q L Wen, J F Huang
OBJECTIVE: To investigate the changes in behavioristics, substantia nigra tyrosine hydroxylase (TH) immunoreactive cells, and ultrastructure of substantia nigra neurons in rats after manganese exposure via intracerebral injection. METHODS: A total of 72 healthy male Sprague-Dawley rats were randomly divided into exposure group and control group, with 36 rats in each group. The stereotactic technique was used for injection of 1 μl MnCl2·4H2O (1 mol/L) into the corpus striatum in the exposure group, and the control group was injected with the same volume of normal saline...
June 20, 2016: Chinese Journal of Industrial Hygiene and Occupational Diseases
Shuzo Orikasa, Kazumi Nabeshima, Noriyuki Iwabuchi, Jin-Zhong Xiao
Schizophrenia is a chronic psychiatric illness. Disruption of the dopaminergic system has been suggested to be the pathogenic cause of this disease. The effect of Bifidobacterium longum BB536 (BB536) on schizophrenic behavior was investigated in an animal model. Daily administration of BB536 (10(9) CFU/mouse, p.o. for 2 weeks) was found to reduce rearing behavior augmented by the dopamine receptor agonist apomorphine and to decrease the resting level of plasma corticosterone and the ratio of kynurenine to tryptophan...
2016: Bioscience of Microbiota, Food and Health
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