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https://www.readbyqxmd.com/read/28106982/a-novel-iron-ii-preferring-dopamine-agonist-chelator-as-potential-symptomatic-and-neuroprotective-therapeutic-agent-for-parkinson-s-disease
#1
Banibrata Das, Ashoka Kandegedara, Liping Xu, Tamara Antonio, Timothy L Stemmler, Maarten E A Reith, Aloke K Dutta
Parkinson's disease (PD) is a progressive neurodegenerative disorder and development of disease-modifying treatment is still an unmet medical need. Considering the implication of free iron (II) in PD, we report here the design and characterization of a novel hybrid iron chelator, (-)-12 (D-607) as a multitarget-directed ligand against PD. Binding and functional assays at dopamine D2/D3 receptors indicate potent agonist activity of (-)-12. The molecule displayed an efficient preferential iron (II) chelation properties along with potent in vivo activity in a reserpinized PD animal model...
January 20, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28104232/dopamine-agonist-withdrawal-syndrome-a-comprehensive-review
#2
REVIEW
Xin Xin Yu, Hubert H Fernandez
Dopamine agonists are effective and widely used treatments for Parkinson disease (PD). However, patients on dopamine agonists may experience significant side effects which necessitate dose tapering or discontinuation. Dopamine agonist withdrawal syndrome (DAWS) is a complication that affects up to 19% of PD patients who undergo a dopamine agonist taper. It was initially described in 2010 as a severe stereotypical cluster of psychiatric and physical symptoms occurring with dopamine agonist withdrawal. Identified risk factors for DAWS include impulse control behavior disorders (ICD) and higher dopamine agonist dosage...
January 2, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28101323/gabapentin-treatment-in-clozapine-induced-restless-legs-syndrome-two-cases-and-a-review-of-the-literature
#3
REVIEW
Vijaya Kumar, Ganesan Venkatasubramanian
Restless legs syndrome (RLS) is a neuro-sensorimotor disorder affecting 2-4% of adults. It is characterized by intense urges to move the legs, associated with unpleasant sensory disturbances in the legs occurring at rest and manifests mostly in the evening and night, relieved by movement. Diagnosis is primarily based on clinical presentation and the consensus criteria for the diagnosis have been established. Antipsychotics, the dopamine antagonists, have been reported to induce RLS. Dopamine agonists, the effective first-line treatment of RLS, carry the risk of inducing or worsening psychosis...
January 2017: Therapeutic Advances in Psychopharmacology
https://www.readbyqxmd.com/read/28101322/brexpiprazole-and-cariprazine-distinguishing-two-new-atypical-antipsychotics-from-the-original-dopamine-stabilizer-aripiprazole
#4
REVIEW
Joshua S Frankel, Thomas L Schwartz
BACKGROUND: Brexpiprazole and cariprazine are the latest US Food and Drug Administration approved atypical antipsychotics available in the United States. Both function as partial agonists of the dopamine-2 receptor (D2R), a mechanism of action shared with aripiprazole. However, all three differ in their affinities for the D2R as well as for serotonin receptors (5-HTRs). This paper seeks to delineate these pharmacodynamic and clinical differences amongst the three dopamine partial agonist atypical antipsychotic drugs...
January 2017: Therapeutic Advances in Psychopharmacology
https://www.readbyqxmd.com/read/28100326/-feeding-difficulty-and-developmental-delay-for-8-months-and-nystagmus-for-4-months-in-an-infant
#5
Jie Zhu, Fei Yu
Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive hereditary disease and is a congenital metabolic disorder of neurotransmitter biosynthesis. It is mainly manifested as hypotonia, oculogyric crisis, autonomic dysfunction, and developmental delay. This article reports a boy manifested as delayed motor development, hypotonia, and oculogyric crisis. Gene screening for metabolic disorders revealed new compound heterozygous mutations, c.1063dupA (p.I355fs) and c.250A>C (p.S84R), in the exon of DDC gene...
January 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28097374/effects-of-5-ht1a-5-ht2a-and-5-ht2c-receptor-agonists-and-antagonists-on-responding-for-a-conditioned-reinforcer-and-its-enhancement-by-methylphenidate
#6
Paul J Fletcher, Fiona D Zeeb, Caleb J Browne, Guy A Higgins, Ashlie D Soko
OBJECTIVES: These experiments examined the effects of selective 5-HT1A, 5-HT2A and 5-HT2C receptor ligands on responding for a conditioned reinforcer (CRf). Effects of these ligands were measured under basal conditions and following elevated dopamine (DA) activity produced by the DA reuptake inhibitor methylphenidate. METHODS: Water-restricted rats learned to associate a conditioned stimulus (CS) with water in operant chambers. Subsequently, two response levers were made available; responding on one lever delivered the CS (now a CRf), while responding on the second lever had no consequences...
January 18, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28096656/analysis-of-pramipexole-dose-response-relationships-in-parkinson-s-disease
#7
Ying Wang, Sheng-Gang Sun, Sui-Qiang Zhu, Chun-Feng Liu, Yi-Ming Liu, Qing Di, Hui-Fang Shang, Yan Ren, Wei Xiang, Sheng-Di Chen
BACKGROUND: Pramipexole (PPX), a non-ergot dopamine receptor agonist, is a first-line treatment for Parkinson's disease (PD). A critical dose level above which a better benefit-to-harm ratio exists has not been examined. METHODS: Chinese PD patients (n=464) were retrospectively analyzed by PPX maintenance dose, PD stage, combined levodopa dose, and baseline tremor contribution. The sum score of Baseline Activities of Daily Living (part II) and Motor Examination (III) of the Unified Parkinson's Disease Rating Scale (UPDRS II+III) was used as a covariate for final score adjustment...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28095073/preclinical-and-potential-applications-of-common-western-herbal-supplements-as-complementary-treatment-in-parkinson-s-disease
#8
Luke A Morgan, Oliver Grundmann
Parkinson's disease (PD) is a neurological disorder with a complex pathological etiology, which is not fully understood. Progression of PD may be the result of a buildup of iron in the substantia nigra, microglia-mediated neuroinflammation, dysfunctional mitochondria, or abnormal protein handling. Dopamine is the main neurotransmitter affected, but as the disease progresses, a decrease in all the brain's biogenic amines occurs. Current medication used in the treatment of PD aims to prevent the breakdown of dopamine or increase dopaminergic neurotransmission in the central nervous system...
January 17, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28092019/urb597-and-the-cannabinoid-win55-212-2-reduce-behavioral-and-neurochemical-deficits-induced-by-mptp-in-mice-possible-role-of-redox-modulation-and-nmda-receptors
#9
Angel Escamilla-Ramírez, Esperanza García, Guadalupe Palencia-Hernández, Ana Laura Colín-González, Sonia Galván-Arzate, Isaac Túnez, Julio Sotelo, Abel Santamaría
Several physiological events in the brain are regulated by the endocannabinoid system (ECS). While synthetic cannabinoid receptor (CBr) agonists such as WIN55,212-2 act directly on CBr, agents like URB597, a fatty acid amide hydrolase (FAAH) inhibitor, induce a more "physiological" activation of CBr by increasing the endogenous levels of the endocannabinoid anandamide (AEA). Herein, we compared the pre- and post-treatment efficacy of URB597 and WIN55,212-2 on different endpoints evaluated in the toxic model produced by the mitochondrial toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice...
January 14, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28089852/dopamine-d1-receptor-agonist-treatment-attenuates-extinction-of-morphine-conditioned-place-preference-while-increasing-dendritic-complexity-in-the-nucleus-accumbens-core
#10
Kendra L Kobrin, Danielle T Arena, Stephen C Heinrichs, Olivia H Nguyen, Gary B Kaplan
The dopamine D1 receptor (D1R) has a role in opioid reward and conditioned place preference (CPP), but its role in CPP extinction is undetermined. We examined the effect of D1R agonist SKF81297 on the extinction of opioid CPP and associated dendritic morphology in the nucleus accumbens (NAc), a region involved with reward integration and its extinction. During the acquisition of morphine CPP, mice received morphine and saline on alternate days; injections were given immediately before each of eight daily conditioning sessions...
January 12, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28089836/delayed-csf-rhinorrhea-after-gamma-knife-radiosurgery-with-or-without-preceding-transsphenoidal-resection-for-pituitary-pathology
#11
Avital Perry, Christopher S Graffeo, William R Copeland, Kathryn M Van Abel, Matthew L Carlson, Bruce E Pollock, Michael J Link
BACKGROUND: Skull base cerebrospinal fluid (CSF) leak after gamma knife radiosurgery (GKRS) is a very rare complication. In patients who were treated with both GKRS and transsphenoidal resection (TSR) for pituitary lesions, early CSF leak occurs at a comparable rate to the general TSR population (4%). Delayed CSF leak occurring more than a year after TSR, GKRS, or dual therapy, is exceedingly rare. METHODS: Retrospective chart review and review of the literature RESULTS: We present two cases of delayed CSF leak following GKRS to treat pituitary adenoma...
January 9, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28074831/rgs9-2-modulates-responses-to-oxycodone-in-pain-free-and-chronic-pain-states
#12
Sevasti Gaspari, Valeria Cogliani, Lefteris Manouras, Ethan M Anderson, Vasiliki Mitsi, Kleopatra Avrampou, Fiona B Carr, Venetia Zachariou
Regulator of G protein signalling 9-2 (RGS9-2) is a striatal enriched signal transduction modulator, known to play a critical role in the development of addiction-related behaviours following exposure to psychostimulants or opioids. RGS9-2 controls the function of several GPCRs, including dopamine and mu opioid (MOR) receptors. We previously showed that RGS9-2 complexes negatively control morphine analgesia, and promote the development of morphine tolerance. In contrast, RGS9-2 positively modulates the actions of other opioid analgesics, such as fentanyl and methadone...
January 11, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28073906/mri-follow-up-is-unnecessary-in-patients-with-macroprolactinomas-and-long-term-normal-prolactin-levels-on-dopamine-agonist-treatment
#13
Juliette Eroukhmanoff, Isabelle Tejedor, Iulia Potorac, Thomas Cuny, Jean Francois Bonneville, Henry Dufour, Georges Weryha, Albert Beckers, Philippe Touraine, Thierry Brue, Frédéric Castinetti
OBJECTIVE Both antitumor and antisecretory efficacies of dopamine agonists (DA) make them the first line treatment of macroprolactinomas. However, there is no guideline for MRI follow-up once prolactin is controlled. The aim of our study was to determine whether a regular MRI follow-up was necessary in patients with long-term normal prolactin levels under DA. PATIENTS AND METHODS We conducted a retrospective multicenter study (Marseille, Paris La Pitie Salpetriere and Nancy, France; Liege, Belgium) including patients with macroprolactinomas (largest diameter > 10 mm, baseline prolactin level > 100 ng/mL) treated by dopamine agonists, and regularly followed (pituitary MRI and prolactin levels) during at least 48 months once normal prolactin level was obtained...
January 10, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28065748/the-effects-of-early-life-stress-on-dopamine-system-function-in-adolescent-female-rats
#14
Iwona Majcher-Maślanka, Anna Solarz, Krzysztof Wędzony, Agnieszka Chocyk
During adolescence, many neural systems, including the dopamine system, undergo essential remodeling and maturation. It is well known that early-life stress (ELS) increases the risk for many psychopathologies during adolescence and adulthood. It is hypothesized that ELS interferes with the maturation of the dopamine system. There is a sex bias in the prevalence of stress-related mental disorders. Information regarding the effects of ELS on brain functioning in females is very limited. In the current study, maternal separation (MS) procedures were carried out to study the effects of ELS on dopamine system functioning in adolescent female rats...
January 5, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28063683/diphasic-dyskinesias-during-levodopa-carbidopa-intestinal-gel-lcig-infusion-in-parkinson-s-disease
#15
Meloni Mario, Solla Paolo, Mascia Mario Marcello, Marrosu Francesco, Cannas Antonino
OBJECTIVES: Levodopa-carbidopa intestinal gel infusion (LCIG) is indicated in patients with advanced levodopa-responsive Parkinson's disease (PD) for the treatment of motor fluctuations and dyskinesias. Here we describe 4 PD patients who developed disabling diphasic dyskinesias after LCIG initiation. METHODS: The clinical data of 33 PD patients consecutively treated with LCIG therapy were obtained through direct clinical observation and detailed review of medical records...
December 31, 2016: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28057530/effects-of-nucleus-accumbens-amphetamine-administration-on-performance-in-a-delay-discounting-task
#16
Caitlin A Orsini, Marci R Mitchell, Sara C Heshmati, Kristy G Shimp, Megan S Spurrell, Jennifer L Bizon, Barry Setlow
Chronic administration of cocaine can cause pronounced and enduring cognitive alterations such as increases in impulsive choice. Chronic cocaine can also result in enhanced dopamine (DA) release in the nucleus accumbens (NAc) in response to reward-related cues. It is possible that this enhanced DA release in the NAc is a mechanism by which cocaine increases impulsive choice. To date, however, the specific role of DA in the NAc in impulsive choice is unclear. To begin to address this, rats received acute microinjections of the indirect DA agonist amphetamine directly into the NAc prior to testing in a delay discounting task in which rats chose between a small, immediate and a large, delayed food reward...
January 3, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28057528/role-of-d2-dopamine-receptors-of-the-ventral-pallidum-in-inhibitory-avoidance-learning
#17
László Lénárd, Tamás Ollmann, Kristóf László, Anita Kovács, Rita Gálosi, Veronika Kállai, Tóth Attila, Erika Kertes, Olga Zagoracz, Zoltán Karádi, László Péczely
In our present experiments, the role of D2 dopamine (DA) receptors of the ventral pallidum (VP) was investigated in one trial step-through inhibitory avoidance paradigm. Animals were shocked 3 times in the conditioning trial, with 0.5mA current for 1s. Subsequently bilateral microinjection of the D2 DA receptor agonist quinpirole was administered into the VP in three doses (0.1μg, 1.0μg or 5.0μg in 0.4μl saline). We also applied the D2 DA receptor antagonist sulpiride (0.4μg in 0.4μl saline) alone or 15min prior to the agonist treatment to elucidate whether the agonist effect was specific for the D2 DA receptors...
January 3, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28057524/involvement-of-presynaptic-5-ht1a-receptors-in-the-low-propensity-of-brexpiprazole-to-induce-extrapyramidal-side-effects-in-rats
#18
Cedric Mombereau, Jørn Arnt, Arne Mørk
Previous studies have shown that partial and full 5-HT1A receptor agonists reduce antipsychotic-induced catalepsy. Consequently, some antipsychotics combining balanced efficacy between dopamine (DA) D2 antagonism or partial agonism and 5-HT1A receptor agonism have a low propensity to induce extrapyramidal side effects (EPS), as reflected by low cataleptogenic activity in rodents. In the present experiments, we attempted to explore the importance of pre- and postsynaptic 5-HT1A agonistic properties of brexpiprazole and aripiprazole in the context of neurological side-effect liabilities...
January 3, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28050719/sudden-benzodiazepine-induced-resolution-of-post-operative-pediatric-cerebellar-mutism-syndrome-a-clinical-spect-study
#19
Francesco Nicita, Milena Paiano, Mauro Liberatore, Alberto Spalice, Paola Papoff, Mariacristina Ullo, Manolo Piccirilli, Anna Clerico, Amalia Schiavetti
Post-operative pediatric cerebellar mutism syndrome (PPCMS) is a clinical syndrome arising from cerebellar injury and characterized by absence of speech and other possible symptoms and signs. Rare reports described some benefit after administration of dopamine agonist therapy, but no treatment has proven efficacy. In this paper, we report on the dramatic, sudden resolution of PPCMS induced by midazolam administration in a boy who underwent posterior fossa surgery for choroid plexus papilloma of the fourth ventricle...
January 3, 2017: Acta Neurochirurgica
https://www.readbyqxmd.com/read/28044942/emerging-pharmacological-therapies-in-schizophrenia-what-s-new-what-s-different-what-s-next
#20
Leslie Citrome
There are several new and emerging medication interventions for both the acute and maintenance treatment phases of schizophrenia. Recently approved are 2 new dopamine receptor partial agonists, brexpiprazole and cariprazine, as well as 2 new long-acting injectable antipsychotic formulations, aripiprazole lauroxil and 3-month paliperidone palmitate. Although differences in efficacy compared to other available choices are not expected, the new oral options offer different tolerability profiles that may be attractive for individual patients who have had difficulties with older medications...
December 2016: CNS Spectrums
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