Antiepileptic Drug Development: II. Anticonvulsant Drug Screening

Epilepsia ◽  
1978 ◽  
Vol 19 (4) ◽  
pp. 409-428 ◽  
Author(s):  
R. L. Krall ◽  
J. K. Penry ◽  
B. G. White ◽  
H. J. Kupferberg ◽  
E. A. Swinyard
Drugs ◽  
2008 ◽  
Vol 68 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Catherine Chiron ◽  
Olivier Dulac ◽  
Gerard Pons

Author(s):  
Shamima Nasreen Ahmed ◽  
Biswajit Das ◽  
Jashabir Chakraborty

Cancer is a disease characterized by uncontrolled proliferation of cells that have transformed from the normal cells of the body. The widely used cancer drugs suffers from the drawback of high toxicity not within the reach of a common man. This urgently necessitating the screening of these compounds. This review focuses on the major contributions of preclinical screening models to anticancer drug development over the years till recent times, from the empirical drug screening of cytotoxic agents against uncharacterized tumor models to the target-orientated drug screening of agents with defined mechanisms of action,, a general transition has been observed. The newer approaches to anticancer drug development involve the molecular characterization of models along with an appreciation of the pharmacodynamics and pharmacokinetic properties of compounds [e. g., the US National Cancer Institute (NCI) in vitro 60-cell line panel, hollow fibre assay, and s. c. xenograft]. In vivo tumor models including orthotopic, metastatic, and genetically engineered mouse models are also reviewed. The preclinical screening efforts of the European are also included. In 2015 with the rapid development of cancer modeling in zebrafish, great opportunities exist for chemical screens to find anticancer drug since 1970 the European Organisation for Research and Treatment of Cancer and Cancer Research UK, have been collaborating with the NCI in the acquisition and screening of compounds.


2003 ◽  
Vol 466 (1-2) ◽  
pp. 99-111 ◽  
Author(s):  
Wolfgang Löscher ◽  
Heidrun Potschka ◽  
Piotr Wlaź ◽  
Wojciech Danysz ◽  
Christopher G Parsons

Author(s):  
Donald F. Weaver

ABSTRACT:There is still no medical cure for epilepsy. Clinical epileptology is in need of a “paradigm shift” when it comes to the continuing development of therapeutics. An important first step in this conceptual evolution is differentiating between the notions of ictogenesis and epileptogenesis. All traditional therapeutics are anti-ictogenic, not antiepileptogenic. The future of antiepileptic drug development lies in the discovery of antiepileptogenics. Just as aspirin is not the drug of choice for meningitis, an anticonvulsant is not the drug of choice for epilepsy. Drug design for epilepsy needs to discover a penicillin, not more aspirins.


2008 ◽  
Author(s):  
◽  
María Elena del Valle

La epilepsia es un grupo heterogéneo de desordenes neurológicos que afecta al 3% de la población mundial. El 30% de los pacientes epilépticos no consigue controlar sus convulsiones con las drogas antiepilépticas (AEDs) disponibles. Existe por lo tanto la necesidad de buscar nuevas AEDs que sean más eficaces y posean menor toxicidad, siendo los productos naturales una alternativa válida como fuente de nuevas estructuras. Eugenia uniflora L (Mirtaceae) es un arbusto ramificado y globoso, utilizado en la medicina tradicional en Brasil, Paraguay y NO de Argentina, sus nombres más comunes son “pitanga” y “ñangapirí” Las hojas desecadas de Eugenia uniflora fueron secadas y molidas. 250 g del polvo fue extraído sucesivamente con hexano y metanol por maceración en frío y se preparó una infusión y un cocimiento (según FNA VI Ed.) del polvo del material vegetal al 5 % y 10% P/V, respectivamente. Los extractos hexánico, metanólico, la infusión y el cocimiento fueron evaluados de acuerdo al Anticonvulsant Drug Development (ADD). Los extractos fueron evaluados en su actividad anticonvulsiva, frente al MES test y PTZ test. El extracto metanólico fue fraccionado por distintas técnicas cromatográficas y las fracciones fueron analizadas por cromatografía líquida de alta resolución (HPLC-DAD) y cromatografía gaseosa acoplada a espectrometría de masas (CG- MS). El extracto metanólico demostró una actividad anticonvulsiva importante, como así también la fracción obtenida por precipitación que presentó una actividad anticonvulsiva 50% efectiva, dando hasta los 30 minutos 75 % efectividad, aumentando el umbral de las convulsiones clónicas inducidas por la administración de PTZsc. Se lograron identificar cuatro compuestos en la fracción activa de Eugenia uniflora.


2019 ◽  
Vol 24 (45) ◽  
pp. 5354-5366 ◽  
Author(s):  
Ranjith Kumar Kankala ◽  
Shi-Bin Wang ◽  
Ai-Zheng Chen

Current preclinical drug evaluation strategies that are explored to predict the pharmacological parameters, as well as toxicological issues, utilize traditional oversimplified cell cultures and animal models. However, these traditional approaches are time-consuming, and cannot reproduce the functions of the complex biological tissue architectures. On the other hand, the obtained data from animal models cannot be precisely extrapolated to humans because it sometimes results in the distinct safe starting doses for clinical trials due to vast differences in their genomes. To address these limitations, the microengineered, biomimetic organ-on-a-chip platforms fabricated using advanced materials that are interconnected using the microfluidic circuits, can stanchly reiterate or mimic the complex tissue-organ level structures including the cellular architecture and physiology, compartmentalization and interconnectivity of human organ platforms. These innovative and cost-effective systems potentially enable the prediction of the responses toward pharmaceutical compounds and remarkable advances in materials and microfluidics technology, which can rapidly progress the drug development process. In this review, we emphasize the integration of microfluidic models with the 3D simulations from tissue engineering to fabricate organ-on-a-chip platforms, which explicitly fulfill the demand of creating the robust models for preclinical testing of drugs. At first, we give a brief overview of the limitations associated with the current drug development pipeline that includes drug screening methods, in vitro molecular assays, cell culture platforms and in vivo models. Further, we discuss various organ-on-a-chip platforms, highlighting their benefits and performance in the preclinical stages. Next, we aim to emphasize their current applications toward pharmaceutical benefits including the drug screening as well as toxicity testing, and advances in personalized precision medicine as well as potential challenges for their commercialization. We finally recapitulate with the lessons learned and the outlook highlighting the future directions for accelerating the clinical translation of delivery systems.


Sign in / Sign up

Export Citation Format

Share Document