Nihon yakurigaku zasshi. Folia pharmacologica Japonica
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Nippon Yakurigaku Zasshi · Sep 2004
Review[Dexmedetomidine hydrochloride (Precedex), a new sedative in intensive care, its pharmacological characteristics and clinical study result].
Dexmedetomidine hydrochloride (Precedex) is a potent and highly selective central alpha(2)-adrenoreceptor agonist. In a test of affinity to receptors in rat brain cortex, this drug showed a high affinity and selectivity to the alpha(2)-adrenoreceptor. This drug induced a dose-dependent decrease in activity, loss of righting reflex, an increase in sedation score, and a dose-dependent prolongation of the latent time of escape from pain in various animal models. ⋯ Similarly, with analgesic action, the ratio of patients who did not require additional morphine medication during intubation was taken as the effective rate. The effective rate for the drug group was significantly high (87.3%; placebo group, 75.0%). The main adverse events observed in the drug group were hypertension and hypotension.
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Nippon Yakurigaku Zasshi · Dec 2003
ReviewTyrosine kinase inhibitor as a therapeutic drug for chronic myelogenous leukemia and gastrointestinal stromal tumor.
The Philadelphia chromosome found in leukemia cells of chronic myelogenous leukemia (CML) patients is produced by translocation between chromosomes 9 and 22, resulting in expression of a chimera protein of Bcr and Abl kinase in the cytoplasm. Bcr-Abl kinase attracted oncology researchers as a molecular target for CML therapy, and a variety of small Abl kinase inhibitors were synthesized. STI571 (imatinib mesylate) was produced by modification of 2-phenylaminopyrimidine, a core structure of protein kinase C inhibitor, to improve selectivity, stability, solubility, and bioavailability. ⋯ Certain point mutations in the ATP binding site were found to be a cause of resistance to STI571 in both Bcr-Abl and c-Kit kinases. Therefore, it would be better to make a precise therapeutic strategy with STI571 based on the gene analysis data. It is also expected that it will be possible to design an inhibitor to overcome such resistance by using the structural information on the mutants.
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Nippon Yakurigaku Zasshi · Feb 2003
Review[Preclinical and clinical profile of imatinib mesilate, a potent protein-tyrosine kinase inhibitor for CML therapy].
Imatinib mesilate (Glivec) is a protein-tyrosine kinase inhibitor that potently inhibits the Bcr-Abl tyrosine kinase as well as the receptors for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-Kit, at in vitro and cellular kinase assay levels. Since Bcr-Abl tyrosine kinase plays a key role in chronic myelogenous leukemia (CML) patients, treatment with imatinib mesilate that potently inhibits Bcr-Abl tyrosine kinase could be a promising therapeutic approach to CML. ⋯ Moreover, in vivo data indicated that imatinib mesilate suppress growth and formation of bcr-abl-positive tumors in mice. As the profile expected from the preclinical studies, imatinib mesilate showed impressive hematological and cytogenic responses in the clinical trials, including interferon-alpha-resistant or intolerant patients.
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Nippon Yakurigaku Zasshi · May 2002
Review[Pharmacological and clinical profile of the free radical scavenger edaravone as a neuroprotective agent].
The involvement of oxygen radical species has been implicated in ischemic and post-ischemic brain cell damage. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one; M. W. 174.20, MCI-186, Radicut Injection) has an inhibitory effect on lipid peroxidation by scavenging free radicals and prevents vascular endothelial cell injury. ⋯ Edaravone improved the core neurological deficits, impaired activities of daily living, and disability, without serious safety problems. Edaravone was approved in Japan for the treatment of acute brain infarction within 24 h after onset in April, 2001. We hope that edaravone represents a promising neuroprotective agent that can contribute to the treatment of acute ischemic stroke.