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Showing papers in "Journal of Pharmacological and Toxicological Methods in 2000"


Journal Article•DOI•
Christopher A. Lipinski1•
TL;DR: There are currently about 10000 drug-like compounds, and true diversity does not exist in experimental combinatorial chemistry screening libraries because current ADME experimental screens are multi-mechanisms, and predictions get worse as more data accumulates.

3,041 citations


Journal Article•DOI•
TL;DR: This review article will focus on the various techniques that are currently employed by drug discovery scientists in evaluating permeability/absorption of drug candidates during the drug candidate selection process.

291 citations


Journal Article•DOI•
TL;DR: This review will assess how computational approaches for ADME parameters have evolved and how they are likely to progress.

244 citations


Journal Article•DOI•
TL;DR: An overview of the basic physiological and pharmacological tenets of blood vessels is given in this article, along with in vivo and in vitro methods used in the measurement of blood flow and blood vessel function.

240 citations


Journal Article•DOI•
TL;DR: The 1980s through 1990s witnessed the widespread incorporation of in vitro absorption, distribution, metabolism, and excretion approaches into drug development by drug companies, which would suggest that the line between discovery and development drug metabolism has blurred.

202 citations


Journal Article•DOI•
TL;DR: The scavenging activities of three standard antioxidants were evaluated and showed that the three standards were efficient and effective in inhibiting both Co(II)/EDTA-induced luminol chemiluminescence and the free radical DPPH*.

198 citations


Journal Article•DOI•
TL;DR: A novel method for measuring the volume of pathologically or artificially induced edema is presented, using the specific gravity of the immersion liquid at equilibrium mass/specific gravity=volume (V).

143 citations


Journal Article•DOI•
TL;DR: Telemeter implantation methods in mice are presently difficult, with relatively low success rates being reported, but validation of new methods, such as the insertion of the catheter tip via the carotid artery, may make the technique more widely accessible in the near future.

122 citations


Journal Article•DOI•
TL;DR: Techniques are described for the mounting of large artery and vein ring segments on wire hooks in an organ bath chamber, following the normalisation routine established by Mulvany and Halpern for small resistance arteries mounted under isometric conditions on a wire myograph.

109 citations


Journal Article•DOI•
TL;DR: This article describes approaches to establishing the multiwell plate-based, direct, fluorometric assays for the activities of the five principal drug-metabolizing enzymes, which are quantitative, rapid, reproducible, and compatible with common high throughput screening instrumentation.

107 citations


Journal Article•DOI•
TL;DR: Animal models will play a primary role in the discovery and characterization of the novel antithrombotic agents that will provide safe and effective pharmacological treatment for life-threatening thrombosis diseases.

Journal Article•DOI•
TL;DR: These newer genomic and proteomic technologies and their analysis and visualization methods have the potential to make the drug discovery and development process less costly and more efficient by aiding to select better target and lead candidates.

Journal Article•DOI•
TL;DR: In vivo methods used for the assessment of venous function in experimental animals and humans are described and critically evaluated to disclose their validity, merits and limitations.

Journal Article•DOI•
TL;DR: The combination of Co(II) and EDTA at pH 9 was found to give the optimum signal with reference to time stability, intensity and reproducibility, and a simple, enzyme-free and time-independent technique is proposed for the detection and quantification of hydrogen peroxide.

Journal Article•DOI•
TL;DR: This review attempts to offer an overview of some of the techniques available for the assessment of regional blood flow in the arterial circulatory system and discusses advantages and disadvantages of these common techniques.

Journal Article•DOI•
TL;DR: The DL-induced inflammation in different models could be used to evaluate anti-inflammatory drugs and almost complete inhibition was produced by mepyramine and cyproheptadine in the pedal oedema model and in the air pouch model.

Journal Article•DOI•
TL;DR: The described techniques provide an experimental model to study xenobiotic induction of rat hepatic and intestinal CYP 3A from the molecular to the catalytic level in individual rats without the need for pooling of tissue.

Journal Article•DOI•
TL;DR: The role of high throughput screening has been and remains the rapid and efficient identification of lead chemical matter within chemical libraries for therapeutics development as discussed by the authors, which has become the focal point for discovery programs within the pharmaceutical industry.

Journal Article•DOI•
TL;DR: In this article, the role of prostaglandins in bone metabolism, the pharmacology of NSAIDs and the modulation of bone metabolism by NSAIDs are discussed, and the current evidence examining the use of nonsteroidal anti-inflammatory drugs in spinal surgery is presented.

Journal Article•DOI•
Shawn C Black1•
TL;DR: In this paper, the authors provide an overview of a number of different cardioprotective strategies that have been successful from a preclinical perspective and also present where possible results of clinical trials of the respective compounds.

Journal Article•DOI•
TL;DR: It is found that the manual glucose assay and the glucose analyzer produced comparable values up to concentrations of about 25 mM, above which samples should be diluted.

Journal Article•DOI•
TL;DR: This manuscript describes a variety of animal models that have been utilized for the exploration of atrial arrhythmia generation and maintenance, as well as models used to evaluate the efficacy of putative antiarrhythmics agents.

Journal Article•DOI•
Michael Gralinski1•
TL;DR: In this paper, the authors discuss the anatomy and physiology surrounding the generation of the electrocardiographic QT interval and the consequences of its alteration and discuss relevant models of preclinical safety and general guidelines for clinical examination in this area.

Journal Article•DOI•
TL;DR: A new animal model combining various elements to provide a broad spectrum of data focussing on the so-called vital physiological functions: cardiovascular, respiratory, and central nervous system that can generate simultaneously a wide range of relevant physiological parameters in conscious rats with a modest requirement for test article.

Journal Article•DOI•
TL;DR: A number of techniques that are used to measure energy substrate metabolism in the isolated perfused heart are overviews and a useful experimental approach that accounts for these variables is described.

Journal Article•DOI•
TL;DR: A mouse model for evaluation of skin anesthesia after infiltration of local anesthetic, and monitoring the vocalization response to electrical stimulus as a measure of analgesia, which is sufficiently sensitive to detect differences between the dose and duration of local anesthesia is described.

Journal Article•DOI•
TL;DR: In this paper, a method for automated registration of the scratching activity of the hind legs of a mouse for periods longer than 24 hours was developed and validated, where metal rings are placed around the hind limbs of mice just above the ankle.

Journal Article•DOI•
TL;DR: It is found that coronary artery ligation, using lidocaine in conjunction with a modified surgical procedure, had a mortality rate of 15%, much lower than reported in previous studies using this model.

Journal Article•DOI•
TL;DR: The JCR:LA-cp rat is compared to other NIDDM models commonly used today to find an animal model expressing complications homologous to the human condition.

Journal Article•DOI•
TL;DR: In this paper, the authors describe a number of techniques that are being used to identify EDHF and present data that address the contribution of a small increase in extracellular K(+) as an EDHF.