Drug development research
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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. ⋯ Ebselen, an antioxidant glutathione peroxidase mimetic, represents a valid and promising example of new potential therapeutic interventions for BD, but the paucity of data warrant further investigation to elucidate its potential efficacy and safety in the management of BPD. Nevertheless, findings provided by the growing field of pharmacogenomic research will ultimately lead to the identification of new molecular targets and safer treatments for BPD. Drug Dev Res 77 : 368-373, 2016. © 2016 Wiley Periodicals, Inc.
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Drug development research · Jun 2015
Effects of acute and sustained pain manipulations on performance in a visual-signal detection task of attention in rats.
Preclinical Research Patients with pain often display cognitive impairment including deficits in attention. The visual-signal detection task (VSDT) is a behavioral procedure for assessment of attention in rodents. Male Sprague Dawley rats were trained in a VSDT and tested with three different noxious stimuli: (i) intraperitoneal injection of lactic acid; (ii) intraplantar injection of formalin; and (iii) intraplantar injection of complete Freund's adjuvant (CFA). ⋯ Although VSDT effects were transient for formalin and absent for CFA, both treatments produced mechanical allodynia and paw edema for up to 7 days. These results support the potential for noxious stimuli to produce a pain-related disruption of attention in rats. However, relatively strong noxious stimulation appears necessary to disrupt performance in this version of the VSDT.
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Drug development research · Dec 2014
Combination of diacerhein and antiepileptic drugs after local peripheral, and oral administration in the rat formalin test.
Preclinical Research The present study was designed to evaluate the possible antinociceptive interaction between diacerhein and some antiepileptic drugs (carbamazepine, topiramate and gabapentin) on formalin-induced nociception. Diacerhein, each of the antiepileptics or a fixed dose-ratio combination of these drugs was assessed after local peripheral and oral administration in rats. lsobolographic analyses were used to define the interaction between drugs. ⋯ These values were significantly higher than the experimentally obtained ED30 values: diacerhein-carbamazepine (49.33 ± 3.37 μg/paw; 35.49 ± 7.91 mg/kg po), diacerhein-topiramate (133.00 ± 39.10 μg/paw; 8.87 ± 1.46 mg/kg po) and diacerhein-gabapentin (70.98 ± 14.73 μg/paw; 10.95 ± 3.23 mg/kg po). The combinations produced their antinociceptive effects without motor impairment in the rotarod test indicating synergistic interactions with a good side effect profile.
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Network representations are widely used in bioinformatics but have only been little explored in chemistry. Thus far, only a few attempts have been made to generate and analyze compound networks. Among these are the first activity cliff networks. ⋯ Recently, a comprehensive activity cliff network has been generated for current public domain bioactive compounds, hence providing a first global view of activity cliff formation. The design of activity cliff networks is discussed herein. From the global activity cliff network, local networks can be extracted for individual compound activity classes that provide graphical access to high-level SAR information for compound optimization efforts.
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Drug development research · Jun 2014
ReviewThe evolving drug development landscape: from blockbusters to niche busters in the orphan drug space.
Strategy, Management and Health Policy Large pharmaceutical companies have traditionally focused on the development of blockbuster drugs that target disease states with large patient populations. However, with large-scale patent expirations and competition from generics and biosimilars, anemic pipelines, escalating clinical trial costs, and global health-care reform, the blockbuster model has become less viable. ⋯ The success of these "niche buster" therapeutics has led to a renewed interest from "Big Pharma" in the rare disease landscape. This article reviews the key drivers for orphan drug research and development, their profitability, and issues surrounding the emergence of large pharmaceutical firms into the orphan drug space.