Search results for "pyridines"
showing 10 items of 310 documents
Behavioral Effects of GABAA Receptor Stimulation and GABA-Transporter Inhibition
2000
Abstract The present analysis addressed behavioral changes after treatment with 4.5 mg/kg or 18.5 mg/kg of the GABA-uptake inhibitor tiagabine combined with either the benzodiazepine diazepam (1.5 mg/kg) or the imidazopyridine zolpidem (0.05 mg/kg), the latter two acting differentially on GABA A receptor subtypes. The study included 97 male PVG/OIaHsd rats. A standard open field, an enriched open field, and an elevated plus-maze was used to study rat behavior. Treatment with the low dose of tiagabine alone induced no specific behavioral effects, whereas the high dose had an anxiolytic-like potential. Furthermore, diazepam but not zolpidem displayed anxiolytic-like effects. Combination of ea…
Early Skin Toxicity as a Predictive Factor for Tumor Control in Hepatocellular Carcinoma Patients Treated with Sorafenib.
2010
Abstract Introduction. Sorafenib is an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases and has led to a longer median overall survival (OS) time and time to progression (TTP) in patients with advanced hepatocellular carcinoma (HCC). This study was conducted to assess the link between the antitumor efficacy of sorafenib and its early cutaneous side effects in advanced HCC patients. Materials and Methods. All patients received 800 mg daily of sorafenib until progression or unacceptable toxicities. We retrospectively analyzed the incidence of rash and hand–foot skin reactions (HFSR) during the first month of treatment, comparing tumor control (partial response …
Dynamic contrast-enhanced MRI parameters as biomarkers for the effect of vatalanib in patients with non-small-cell lung cancer.
2014
ABSTRACT: Aims: To assess the utility of dynamic contrast-enhanced MRI parameters in the demonstration of early antiangiogenic effects and as prognostic biomarkers in second-line treatment of advanced-stage non-small-cell lung cancer with vatalanib. Patients & methods: The transfer constant (Ktrans) and the initial area under the contrast concentration–time curve at 60 s (AUC60) were assessed in 46 patients. Changes were compared with response evaluation from computed tomography imaging and Response Evaluation Criteria In Solid Tumors guidelines. Results: Statistically significant mean reductions in Ktrans (38.4%; p < 0.0001) and AUC60 (24.9%; p < 0.0001) were found at day 2. Af…
Search for Stroke-Protecting Agents in Endothelin-1-Induced Ischemic Stroke Model in Rats
2012
Background and Objective. Ischemic stroke may initiate a reperfusion injury leading to brain damage cascades where inflammatory mechanisms play a major role. Therefore, the necessity for the novel stroke-protecting agents whose the mechanism of action is focused on their anti-inflammatory potency is still on the agenda for drug designers. Our previous studies demonstrated that cerebrocrast (a 1,4-dihydropyridine derivative) and mildronate (a representative of the aza-butyrobetaine class) possessed considerable anti-inflammatory and neuroprotective properties in different in vitro and in vivo model systems. The present study investigated their stroke-protecting ability in an endothelin-1 (ET…
Distinct influence of atypical 1,4-dihydropyridine compounds in azidothymidine-induced neuro- and cardiotoxicity in mice ex vivo.
2008
This study demonstrates the effective protection by compounds of atypical 1,4-dihydropyridine (DHP) series cerebrocrast, glutapyrone and tauropyrone against neuro- and cardiotoxicity caused by the model compound azidothymidine, a well-known mitochondria-compromising anti-HIV drug. In previous in vitro experiments, we have demonstrated distinct effects of these DHP compounds to influence mitochondrial functioning. In the present in vivo experiments, DHP compounds were administered intraperitoneally in mice daily for 2 weeks, per se and in combinations with azidothymidine at doses: azidothymidine 50 mg/kg; cerebrocrast 0.1 mg/kg; glutapyrone 1 mg/kg; and tauropyrone 1 mg/kg. At the end of the…
Computer-guided drug repurposing: Identification of trypanocidal activity of clofazimine, benidipine and saquinavir
2015
In spite of remarkable advances in the knowledge on Trypanosoma cruzi biology, no medications to treat Chagas disease have been approved in the last 40 years and almost 8 million people remain infected. Since the public sector and non-profit organizations play a significant role in the research efforts on Chagas disease, it is important to implement research strategies that promote translation of basic research into the clinical practice. Recent international public-private initiatives address the potential of drug repositioning (i.e. finding second or further medical uses for known-medications) which can substantially improve the success at clinical trials and the innovation in the pharmac…
4-Aminopyridine antagonizes the inhibitory effect of pentobarbital on acetylcholine release in the heart
1980
Effects of pentobarbital on acetylcholine (ACh) release, force of contraction and nervous conduction were studied in isolated heart preparations and in cervical vagus nerves, respectively. 4-Aminopyridine and tetracaine were used as pharmacological tools to eludicate the mode of action of pentobarbital. 1. 4-Aminopyridine (10−4 M) markedly increased the overflow of ACh from the isolated chicken heart evoked by electrical stimulation (1–50 Hz, 1 ms, 40 V) of the cervical vagus nerves. This effect of 4-aminopyridine was highest at low frequencies of stimulation (+ 226% at 1 Hz) and declined with increasing frequencies to reach a minimum augmentation of 22% at 30 Hz. 2. Pentobarbital and tetra…
Efficacy of an insecticide paint against insecticide-susceptible and resistant mosquitoes - Part 1: Laboratory evaluation
2010
Abstract Background The main malaria vector Anopheles gambiae and the urban pest nuisance Culex quinquefasciatus are increasingly resistant to pyrethroids in many African countries. There is a need for new products and strategies. Insecticide paint Inesfly 5A IGR™, containing two organophosphates (OPs), chlorpyrifos and diazinon, and insect growth regulator (IGR), pyriproxyfen, was tested under laboratory conditions for 12 months following WHOPES Phase I procedures. Methods Mosquitoes used were laboratory strains of Cx. quinquefasciatus susceptible and resistant to OPs. The paint was applied at two different doses (1 kg/6 m2 and 1 kg/12 m2) on different commonly used surfaces: porous (cemen…
Regulation of α4β2α5 nicotinic acetylcholinergic receptors in rat cerebral cortex in early and late adolescence: Sex differences in response to chron…
2013
Chronic nicotine administration in animals, and smoking in humans, causes up-regulation of α4β2* neuronal nicotinic receptors (nAChRs), which has been hypothesized to contribute to the addictive actions of nicotine. We used a rat model to test whether such up-regulatory effects differ in adolescents versus adults, and in males versus females. Following chronic treatment with nicotine or saline via subcutaneous osmotic minipumps, we measured α4β2 and α4β2α5 nAChRs in cerebral cortex using [3H]epibatidine to label assembled nAChRs, and selective antibodies to measure the individual subunits via immunoprecipitation. For the first time, we provide a detailed characterization of the response of …
Cabozantinib in Pretreated Patients with Metastatic Renal Cell Carcinoma with Sarcomatoid Differentiation: A Real-World Study
2021
Background: Renal cell carcinoma with sarcomatoid differentiation is a highly aggressive form of kidney cancer. Objective: We aimed to analyze the outcomes of patients treated with cabozantinib for metastatic renal cell carcinoma with sarcomatoid features. Methods: We retrospectively collected data from 16 worldwide centers. Overall survival and progression-free survival were analyzed using Kaplan–Meier curves. Cox proportional models were used for univariate and multivariate analyses. Results: We collected data from 66 patients with metastatic sarcomatoid renal cell carcinoma receiving cabozantinib as second-line (51%) or third-line (49%) therapy. The median progression-free survival from …