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Drug Development Research

Israel Barreras-Espinoza, José Alberto Soto-Zambrano, Nicolás Serafín-Higuera, Ramón Zapata-Morales, Ángel Alonso-Castro, Ronell Bologna-Molina, Vinicio Granados-Soto, Mario A Isiordia-Espinoza
Preclinical Research The aim of the present study was to evaluate the antinoceptive interaction between the opioid analgesic, tapentadol, and the NSAID, ketorolac, in the mouse orofacial formalin test. Tapentadol or ketorolac were administered ip 15 min before orofacial formalin injection. The effect of the individual drugs was used to calculate their ED50 values and different proportions (tapentadol-ketorolac in 1:1, 3:1, and 1:3) were assayed in the orofacial test using isobolographic analysis and interaction index to evaluate the interaction between the drugs...
December 16, 2016: Drug Development Research
Claudia Vergelli, Igor A Schepetkin, Giovanna Ciciani, Agostino Cilibrizzi, Letizia Crocetti, Maria Paola Giovannoni, Gabriella Guerrini, Antonella Iacovone, Liliya N Kirpotina, Richard D Ye, Mark T Quinn
Preclinical Research Formyl peptide receptors (FPRs) are G-protein-coupled receptors that play an important role in the regulation of inflammatory process and cellular dysfunction. In humans, three different isoforms are expressed (FPR1, FPR2, and FPR3). FPR2 appears to be directly involved in the resolution of inflammation, an active process carried out by specific pro-resolving mediators that modulate specific receptors. Previously, we identified 2-arylacetamido pyridazin-3(2H)-ones as FPR1- or FPR2-selective agonists, as well as a large number of mixed-agonists for the three isoforms...
November 18, 2016: Drug Development Research
David Feifel
Preclinical Research The surprising results of a small clinical trial on the effects of low dose ketamine, a 65-year old anesthetic drug that is also used off-label for chronic pain and recreationally as a club drug, in eight depressed subjects unleashed the most significant advance in antidepressant drug development in decades. That study and subsequent ones have demonstrated that low dose, infused ketamine is able to induce a remission of depression in patients who have failed conventional medications, within 24 h...
December 2016: Drug Development Research
Cornelis J Van der Schyf
Preclinical Research Neuropsychiatric symptoms are currently recognized as a common burden in patients suffering from Alzheimer's disease (AD), Parkinson's disease (PD), and many other neurodegenerative disorders. Earlier theories positing that these symptoms emerge predominantly in patients with late-stage disease have been largely dismissed. It is now generally accepted that many neuropsychiatric symptoms commonly manifest very early in neurodegenerative disease stages, and in many cases are even considered prodromal indicators...
December 2016: Drug Development Research
Ashish Sharma, Rohit Goyal
Preclinical Research Circadian rhythms are fundamental processes in all cells that coordinate a variety of cellular functions related to a specific time of the day. Disruption of circadian rhythms markedly impacts homeostasis. In this Commentary, we present data that disruption of circadian rhythm may lead to the pathogenesis of neurodegenerative states. In this context, we further argue that there is an urgent need of developing new generations of compounds, chronobiotics, to modulate the molecular substrates of circadian timing system...
December 2016: Drug Development Research
Elena Milanesi, Carlo Maj, Luisella Bocchio-Chiavetto, Elisabetta Maffioletti
Preclinical Research Alterations in small non-coding RNAs have been observed in many human disease states including cancer, cardiovascular, developmental, neurological, and psychiatric disorders. These molecules have recently raised the interest of the scientific community for novel therapeutic approaches. Nanotechnologies, including the development of sophisticated nanoparticles, offer new ways for the delivery of small RNA-based therapies. The nanoparticle delivery method appears attractive, but so far most of the work in this area has been conducted in the context of cancer...
December 2016: Drug Development Research
Michela Brambilla, Rosa Manenti, Giovanni de Girolamo, Mauro Adenzato, Luisella Bocchio-Chiavetto, Maria Cotelli
Preclinical Research The neuropeptide oxytocin (Oxt) is implicated in complex emotional and social behaviors and appears to play an important role in learning and memory. Animal studies have shown that the effects of exogenous Oxt on memory vary according to the timing of administration, context, gender, and dose and may improve the memory of social, but not nonsocial stimuli. Oxt is intimately involved in a broad array of neuropsychiatric functions and may therefore be a pharmacological target for several psychiatric disorders...
December 2016: Drug Development Research
Sarah Khan, Vijaylaxmi Rathore, Shahida Khan
Preclinical Research Recent advances in pediatric psychopharmacology have been rather uneven. Increased use of psychotropic drugs among the pediatric population has raised concerns regarding their inappropriate use and safety. While clinical trials have been conducted on various pediatric psychopharmacological drugs, there has been an insignificant amount of importance to innovation in holistic treatment. A rational approach toward elucidating the various challenges would be contingent on the convergence of the development of novel efficacious psychotropic drugs with concrete conceptual frameworks and guidelines fostering enhanced outcomes...
December 2016: Drug Development Research
Zi-Jun Wang, Jian-Feng Liu
Preclinical Research Insomnia is one of the most common sleep disorders that is characterized by difficulty in sleep initiation, sleep maintenance, and/or poor sleep quality. Treatment for insomnia includes both pharmacological and non-pharmacological interventions. Recently, the development of pharmacological treatment for insomnia has been prompted by the understanding of the molecular neurobiology of sleep-wake regulation. For pharmacological treatment, benzodiazepines that target GABAergic system are the most widely used hypnotics...
December 2016: Drug Development Research
Marco Cavallo, Arianna Signorino, Maria Luisa Perucchini
Preclinical Research Mild Cognitive Impairment (MCI) now termed Mild Neurocognitive Disorder (MCD) in DSM-5, is widely used to define the disorder in individuals who have subjective cognitive deficits, objective memory impairments, or other cognitive deficits, without impairments in daily activities. Cognitive enhancers such as the acetylcholinesterase inhibitors, commonly used with some benefit in overt dementia, have recently started to be used in MCI/MCD. Treatment of disorders associated with cognitive dysfunction represents an expanding area of neurological rehabilitation and continues to be of paramount importance from political, social and ethical perspectives...
December 2016: Drug Development Research
Andrea Milelli, Eleonora Turrini, Elena Catanzaro, Francesca Maffei, Carmela Fimognari
Preclinical Research A novel and promising approach to overcome the limits of single-target therapy is represented by the multitarget approach. This strategy aims to simultaneously modulate several targets involved in the pathophysiology of a multifactorial disease, with the potential to enhance therapeutic effectiveness and improve drug safety. Although there has been a marked growth in the design of multitarget drugs (MTDs) in the last years in the context of anti-Alzheimer and anti-cancer drug discovery, a parallel expansion was not observed in antipsychotic drugs, even that for psychiatric disorders there is a cogent medical need for new treatments...
December 2016: Drug Development Research
Violina Angelova, Valentin Karabeliov, Pavlina A Andreeva-Gateva, Jana Tchekalarova
Preclinical Research Epilepsy is a chronic devastating neurological disorder characterized by synchronous interictal discharges. Treatment with antiepileptic drugs (AEDs) can alleviate spontaneous seizure activity without preventing the progression and development of epileptogenesis. Current design and development of new AEDs and strategies for the prevention of epilepsy is focused mainly on attenuating uncontrolled seizures, severe side effects and toxicity in chronic drug therapy. It has thus become necessary to discover new chemical pharmacophores with a broad spectrum of activity and less neurotoxicity...
November 2016: Drug Development Research
Carmel Bilu, Haim Einat, Noga Kronfeld-Schor
Preclinical Research Most neuropsychiatric research, including that related to the circadian system, is performed using nocturnal animals, mainly laboratory mice and rats. Mood disorders are known to be associated with circadian rhythm abnormalities, but the mechanisms by which circadian rhythm disruptions interact with depression remain unclear. As the circadian system of diurnal and nocturnal mammals differs, we previously suggested that the utilization of diurnal animal models may be advantageous for understanding these relations...
November 2016: Drug Development Research
Claudia Pisanu, Carla Melis, Alessio Squassina
Preclinical Research Bipolar disorder (BPD) is a chronic and disabling psychiatric disorder with a prevalence of 0.8-1.2% in the general population. Although lithium is considered the first-line treatment, a large percentage of patients do not respond sufficiently. Moreover, lithium can induce severe side effects and has poor tolerance and a narrow therapeutic index. The genetics of lithium response has been largely investigated, but findings have so far failed to identify reliable biomarkers to predict clinical response...
November 2016: Drug Development Research
Nadja P Maric, Milica J Jovicic, Marina Mihaljevic, Cedo Miljevic
Preclinical Research After the identification of the schizophrenia as an illness over a century ago, treatment of affected individuals included unspecific, mostly very robust methods including deep insulin coma and lobectomy/leucotomy. The first relatively specific treatment of schizophrenia started about 60 years ago with the antipsychotic chlorpromazine. All currently approved antipsychotic drugs block dopamine receptors, indicating that manipulation of dopaminergic function is fundamental to a therapeutic response in psychosis...
November 2016: Drug Development Research
Nataša Karas Kuželički
Preclinical Research S-adenosyl methionine (SAM) is a major methyl donor and as such exerts its influence on CNS function through methylation reactions, such as methylation of several catecholamine moiety-containing neurotransmitters, epigenetic changes through methylation of DNA, RNA, RNA-binding proteins and histones, and phospholipid methylation. Based on available evidence, SAM is currently recommended as a next-step (second-line) treatment option following inadequate treatment response to a first-line antidepressant...
November 2016: Drug Development Research
Seher Karsli-Ceppioglu
Preclinical Research Epigenetic mechanisms refer covalent modification of DNA and histone proteins that control transcriptional regulation of gene expression. Epigenetic regulation is involved in the development of the nervous system and plays an important role in the pathophysiology of psychiatric disorders, including depression, bipolar disorder, and schizophrenia. Epigenetic drugs, including histone deacetylation and DNA methylation inhibitors have received increased attention for the management of psychiatric diseases...
November 2016: Drug Development Research
David Gurwitz
No abstract text is available yet for this article.
November 2016: Drug Development Research
Vesna Pešić, Jelena Petrović, Marin M Jukić
Preclinical Research The emergence of rapid-acting antidepressants such as ketamine has motivated studies aiming to reveal the molecular mechanism of the ketamine antidepressant effect and to enable the clinical application of rapid-acting antidepressants. Here, we provide an overview of studies addressing the antidepressant effects of ketamine in depressed patients and animal models of depression and we compare the reduction of depressive symptoms in humans with the reduction in immobility time in the forced swim test in rodents after acute ketamine treatment...
November 2016: Drug Development Research
Yuan Sun, Chen Kang, Fei Liu, Lei Song
Preclinical Research Psychosis remains one of the most challenging health problems for society, affecting hundreds of millions of people worldwide. Although current antipsychotics can alleviate the symptoms of psychosis, they are still far away from being perfect, often causing significant and even fatal side effects such as involuntary movement disorders and metabolic syndrome. With the lack of precise knowledge of the underlying mechanisms of psychosis, a rational approach to improve the efficiency of current antipsychotics is by nanoparticle-based administration...
November 2016: Drug Development Research
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