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Extrapyramidal side effects

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
Tafheem Malik, Sheema Hasan, Shahid Pervez, Tasneem Fatima, Darakhshan Jabeen Haleem
The symptoms of Parkinsonism and oral dyskinesia have been showing to be induced by neuroleptics that significantly affect its clinical use. In this study, we investigate whether Nigella sativa-oil (NS) (black cumin seeds)-a traditional medicine used for the seizure treatment in eastern country-may reduce the haloperidol (HAL)-induced extrapyramidal symptoms (EPS)-like behavior in rats. After combine treatment with HAL (1 mg/kg) on NS (0.2 ml/rat), rats displayed a significant decreased EPS-like behavior including movement disorders and oral dyskinesia as compared to controls...
October 18, 2016: Neurochemical Research
Daniel Lampignano, Taral R Sharma
No abstract text is available yet for this article.
2016: Primary Care Companion to CNS Disorders
Saeed Shoja Shafti, Abbas Azizi Khoei
BACKGROUND: Several lines of evidence suggest that the cholinergic system may be disrupted in schizophrenia and so this may contribute to the cognitive impairments of schizophrenic patients. Because such deficits do not respond to neuroleptic treatment, different approaches have been done by acetylcholinesterase inhibitors (AChEIs). The objective of the present assessment was to evaluate the safety and clinical effects of rivastigmine, as an adjunctive drug, on the clinical symptoms of schizophrenia...
October 2016: Therapeutic Advances in Psychopharmacology
Travis T Wager, Thomas A Chappie, David Horton, Ramalakshmi Y Chandrasekaran, Brian M Samas, Elizabeth Dunn-Sims, Cathleen Hsu, Nawshaba Nawreen, Michelle A Vanase-Frawley, Rebecca E O'Connor, Christopher Schmidt, Keith Dlugolenski, Nancy C Stratman, Mark J Majchrzak, Bethany L Kormos, David Nguyen, Aarti Sawant-Basak, Andy N Mead
Dopamine receptor antagonism is a compelling molecular target for the treatment of a range of psychiatric disorders, including substance use disorders. From our corporate compound file we identified a structurally unique D3 receptor (D3R) antagonist scaffold, 1. Through a hybrid approach, we merged key pharmacophore elements from 1 and D3 agonist 2 to yield the novel D3R/D2R antagonist PF-4363467 (3). Compound 3 was designed to possess CNS drug-like properties as defined by its CNS MPO desirability score (≥4/6)...
October 7, 2016: ACS Chemical Neuroscience
I Mouch, J R B J Brouwers, E van 't Riet, P Nieboer, M H Otten, F G A Jansman
OBJECTIVE: To investigate whether the anti-emetics metoclopramide and domperidone can be replaced by 5-HT3-antagonists, as side effects restrict use of these dopamine antagonists. DESIGN: Systematic review. METHOD: We searched the Embase and PubMed databases for articles published in the period 1995-October 2015, in which the efficacy or side effects of metoclopramide or domperidone were compared with at least one of the 5-HT3-antagonists ondansetron, granisetron, tropisetron or palonosetron...
2016: Nederlands Tijdschrift Voor Geneeskunde
Keita Arakawa, Kazunari Nakao, Shunsuke Maehara
Inhibition of phosphodiesterase 10A (PDE10A) results in activation of a dopamine D1 receptor-mediated direct pathway in addition to a dopamine D2 receptor-mediated indirect pathway in the striatum. Therefore, PDE10A inhibitors could be novel therapeutics for schizophrenia, which differ from the currently available antipsychotics that directly block the dopamine D2 receptor. Previously, we found that a novel PDE10A inhibitor, PDM-042, had antipsychotic-like activity similar to currently available antipsychotics and minimal cataleptic effects in rats...
September 19, 2016: Behavioural Brain Research
Simon Gilbody, Anne-Marie Bagnall, Lorna Duggan, Arja Tuunainen
BACKGROUND: Risperidone is one of a number of 'atypical antipsychotics' which are currently being marketed for the treatment of those with schizophrenia, largely on the basis of claims of improved tolerability and effectiveness compared to much cheaper conventional antipsychotics. The efficacy of risperidone has already been compared to conventional drugs, but it remains unclear how risperidone compares with other atypical antipsychotic drugs such as clozapine. OBJECTIVES: To determine the effects of risperidone compared with other atypical antipsychotic drugs for schizophrenia...
September 20, 2016: Cochrane Database of Systematic Reviews
Kim S J Lao, Ying He, Ian C K Wong, Frank M C Besag, Esther W Chan
BACKGROUND: Cariprazine is a novel antipsychotic agent recently approved for treating schizophrenia and bipolar mania in the USA. The sample sizes of published randomized controlled trials (RCTs) of the drug are small; previous meta-analyses included few RCTs and did not specifically investigate the tolerability/safety profile of cariprazine. OBJECTIVE: Our objective was to conduct a meta-analysis of published RCTs to systematically review the tolerability and safety of cariprazine versus placebo...
August 22, 2016: CNS Drugs
Erum Shireen
Antipsychotic drugs are extensively prescribed for the treatment of schizophrenia and other related psychiatric disorders. These drugs produced their action by blocking dopamine (DA) receptors, and these receptors are widely present throughout the brain. Therefore, extended antipsychotic use also leads to severe extrapyramidal side effects. The short-term effects include parkinsonism and the later appearing tardive dyskinesia. Currently available treatments for these disorders are mostly symptomatic and insufficient, and are often linked with a number of detrimental side effects...
2016: Journal of Experimental Pharmacology
E Unti, S Mazzucchi, G Palermo, U Bonuccelli, R Ceravolo
INTRODUCTION: The aim of this review is to overview the pharmacological features of neuroleptics experienced in the treatment of Huntington's disease (HD) symptoms. Despite a large number of case reports, randomized controlled trials (RCT) and drug comparison studies are lacking. AREAS COVERED: After evaluating current guidelines and clinical unmet needs we searched PubMed for the term 'Huntington's disease' cross referenced with the terms 'Antipsychotic drugs' 'Neuroleptic drugs' and single drug specific names...
August 23, 2016: Expert Review of Neurotherapeutics
Gerda M de Kuijper, Pieter J Hoekstra
Drug-associated extrapyramidal symptoms (EPS) in people with intellectual disability (ID) may be difficult to recognize, and clinicians' assessments may be hampered by lack of patients' capacities to adequately cooperate and by lack of reliable instruments to measure EPS in this population. Therefore, we compared assessments based on professional caregivers' observations with the informant-based validated Matson Evaluation of Drug Side Effects (MEDS) scale with assessments by clinicians using a set of clinical rating scales, most of which have not been validated for use in this population...
October 2016: Journal of Clinical Psychopharmacology
André F Carvalho, Manu S Sharma, André R Brunoni, Eduard Vieta, Giovanni A Fava
Newer generation antidepressant drugs (ADs) are widely used as the first line of treatment for major depressive disorders and are considered to be safer than tricyclic agents. In this critical review, we evaluated the literature on adverse events, tolerability and safety of selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors, bupropion, mirtazapine, trazodone, agomelatine, vilazodone, levomilnacipran and vortioxetine. Several side effects are transient and may disappear after a few weeks following treatment initiation, but potentially serious adverse events may persist or ensue later...
2016: Psychotherapy and Psychosomatics
Adam J Prus, Laura E Wise, Alan L Pehrson, Scott D Philibin, Benny Bang-Andersen, Jørn Arnt, Joseph H Porter
The atypical antipsychotic drug clozapine remains one of most effective treatments for schizophrenia, given a lack of extrapyramidal side effects, improvements in negative symptoms, cognitive impairment, and in symptoms in treatment-resistant schizophrenia. The adverse effects of clozapine, including agranulocytosis, make finding a safe clozapine-like a drug a goal for drug developers. The drug discrimination paradigm is a model of interoceptive stimulus that has been used in an effort to screen experimental drugs for clozapine-like atypical antipsychotic effects...
October 1, 2016: Brain Research
Changqing Xu, Jegan Yogaratnam, Nigel Tan, Kang Sim
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterized by a triad of progressive motor dysfunction, cognitive decline and psychiatric disturbances. The hallmark of HD is the distinctive choreiform movement disorder that typically has a subtle, insidious onset in the fourth to fifth decade of life and gradually worsens over 10 to 20 years until death. Notably, two-thirds of HD patients present with chorea and one third with mental changes. The prevalence of psychiatric symptoms is significantly higher than in the general population, and is estimated to be around 66-73%...
August 31, 2016: Clinical Psychopharmacology and Neuroscience: the Official Scientific Journal of the Korean College of Neuropsychopharmacology
Iveta Šimić, Ines Potočnjak, Iva Kraljičković, Mirjana Stanić Benić, Ivana Čegec, Danica Juričić Nahal, Lana Ganoci, Nada Božina
A 66-year-old male Caucasian, received 1 mg of haloperidol orally and rapidly developed severe iatrogenic extrapyramidal symptoms. Treatment was immediately discontinued, and the side effects resolved. Haloperidol is mainly metabolized by Phase I CYP2D6 and to the lesser extent by CYP3A4 and by Phase II UGT2B7 enzymes. Genotyping was performed revealing CYP2D6*6/*6, CYP3A4*1/*1, and UGT2B7 -161 C/T genotypes, implicating poor, extensive and intermediate metabolism, respectively. Of the CYPs, haloperidol is metabolized by CYP2D6 and CYP3A4 primarily...
August 2016: Pharmacogenomics
Akira Wada, Yasuto Kunii, Jyunya Matsumoto, Mizuki Hino, Atsuko Nagaoka, Shin-Ichi Niwa, Hirooki Yabe
BACKGROUND: The calcineurin (CaN) inhibitor, tacrolimus, is widely used in patients undergoing allogeneic organ transplantation and in those with certain allergic diseases. Recently, several reports have suggested that CaN is also associated with schizophrenia. However, little data are currently available on the direct effect of tacrolimus on the human brain. CASE: A 23-year-old Japanese female experienced severe delusion of persecution, delusional mood, suspiciousness, aggression, and excitement...
2016: Neuropsychiatric Disease and Treatment
Geancarlo Zanatta, Gustavo Della Flora Nunes, Eveline Matias Bezerra, Roner F da Costa, Alice Maria Martins, Ewerton Wagner Santos Caetano, Valder Nogueira Freire, Carmem Gottfried
Risperidone is an atypical antipsychotic used in the treatment of schizophrenia and of symptoms of irritability associated with autism spectrum disorder (ASD). Its main action mechanism is the blockade of D2-like receptors acting over positive and negative symptoms of schizophrenia with small risk of extrapyramidal symptoms (EPS) at doses corresponding to low/moderate D2 occupancy. Such decrease in the side effect incidence can be associated to its fast unbinding from D2 receptors in the nigrostriatal region allowing the recovery of dopamine signaling pathways...
July 19, 2016: ACS Chemical Neuroscience
Marina de Tommaso, Miriam Kunz, Massimiliano Valeriani
INTRODUCTION: Neurodegenerative diseases are increasing in parallel to the lengthening of survival. The management of Alzheimer's disease (AD) and other dementias, Parkinson's disease (PD) and PD-related disorders, and motor neuron diseases (MND), is mainly targeted to motor and cognitive impairment, with special care for vital functions such as breathing and feeding. AREAS COVERED: The present review focuses on chronic pain in main neurodegenerative diseases, addressing current evidence on pain therapeutic management, pain frequency and clinical features, and possible pathophysiological mechanisms...
July 26, 2016: Expert Review of Neurotherapeutics
H Belli, M Akbudak, Z E Bal
Rabbit syndrome is an extrapyramidal side effect which is described as a variant of tardive dyskinesia. Rabbit syndrome is characterized by rapid, rhytmic orofacial movements, often accompanied by lip sounds. This movement disorder may be associated with either typical or atypical antipsychotic agents. The index case presented to our clinic with the complaints of bipolar depression. In addition to valproate, quetiapine was started with the dose of 50 mg per day, which was increased to 300 mg per day within two weeks for depression...
December 14, 2015: West Indian Medical Journal
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