[High throughput pharmacology for drug discovery].
High Throughput Screening (HTS) now plays an important role in the discovery of new lead compounds for novel therapeutic targets. The advantage of HTS over the conventional method, now termed as Low Throughput Screening (LTS), is that valuable compounds can be selected rapidly from a large number of samples with minimal human involvement. In spite of the growing awareness of HTS, the importance of the LTS in the drug discovery and development is still not changed. Advances in pharmacogenomics will also provide us many pharmacological targets, and thus increase the number of compounds that should be assayed by HTS and LTS. In this review, we will first describe the outline of HTS. We will next describe new approaches to develop and brush up the LTS: 1) screening method of drugs acting on ion channels by voltage-sensitive fluorescent dye, 2) functional assay method using reconstituted smooth muscle fiber, and 3) organ culture method as a useful model of vascular proliferative disease. These approaches, which work cooperatively with HTS, will contribute greatly to the development of new drugs.
Ozaki
H
H
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan. aozaki@mail.ecc.u-tokyo.ac.jp
Imaizumi
Y
Y
Oishi
K
K
Kohama
K
K
D000818:Animals; D001322:Autoanalysis; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D023281:Genomics; D006801:Humans; D007473:Ion Channels; D009130:Muscle, Smooth; D020411:Oligonucleotide Array Sequence Analysis; D009924:Organ Culture Techniques; D010597:Pharmacogenetics; D012371:Robotics; D013678:Technology, Pharmaceutical / Q000379:methods*
D007473:Ion Channels