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Volume 114, Issue 2
Displaying 1-3 of 3 articles from this issue
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Makoto HOSONO1999 Volume 114 Issue 2 Pages 83-88
Published: 1999
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSColforsin daropate hydrochloride (COL) is a water-soluble forskolin derivative for the treatment of acute heart failure. COL, like forskolin, stimulated adenylate cyclase (AC) directly and produced pharmacologic activities accompanied by the increase in cellular cAMP. COL was different from forskolin in water-solubility, duration of action, BBB permeability, oral activity and AC-subtype selectivity. COL was a inodilator with positive inotropic and vasodilator effects and was effective on a β-receptor desensitized-heart model in which the effects of β-agonists and PDE inhibitors were attenuated. COL improved cardiac function in some heart failure models. In the clinical studies, COL improved hemodynamics, subjective and objective symptoms of heart failure patients, and was also effective in the catecholamine-resistaiit heart failure patients. COL is a first clinically available adenylate cyclase activator. Further information from the post-marketing-surveillance will provide information that will enable more adequate usage of this drug.View full abstractDownload PDF (6376K) -
Kenji ONODERA, Shuichi MIYAZAKI1999 Volume 114 Issue 2 Pages 89-106
Published: 1999
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSHistamine H3 receptors exist in the presynapse of histaminergic nerve terminals, and they regulate the synthesis and release of histamine. A high density of histamine H3 receptors is observed in the cerebral cortex, the amygdala, the striatum, the hippocampus, the thalamus and the hypothalamus. In this review, we describe signal transduction mechanisms of histamine H3 receptors and discuss the structure-activity relationship of histamine H3-receptor ligands, including new compounds that possess high selectivities and affinities. Possible roles of histamine H3 receptors on neurobehavioral disorders such as Alzheimer's disease, Down syndrome, attention deficit hyperactive disease, epilepsy, stress, anxiety, Parkinson's disease, etc. were also described. Recent pharmacological studies revealed that BP2.94, a histamine H3 receptor agonist, has anti-inflammatory and analgesic action. BP2.94 may be useful for the treatment of migraine and is now in clinical trial. Histamine H3 receptor antagonists such as GT2016 and FUB181 may provide clinical candidates for the treatment of dementia, attention deficit hyperactive disorder and epilepsy.View full abstractDownload PDF (20862K) -
Hiroaki SANO, Hideo UTSUMI1999 Volume 114 Issue 2 Pages 107-114
Published: 1999
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSIt was proven that in vivo free radicals roles in various physiological phenomena and many diseases such as inflammation, ischemic disease, digestive problems and neurodegeneration, thus making measurements of free radicals very important for determining the mechanisms of these diseases. Spin trapping method using ESR, salicylic acid methods using high performance liquid chromatography and chemiluminescent methods are reported for ex vivo and in situ measurements. And, among these techniques, in vivo ESR is the most powerful for performing non-invasive measurements in animals. In in vivo ESR, exogenous nitroxyl radicals are administered to animal and then by measuring the signal change, the radical reaction can be indirectly determined. The signal decay rate is enhanced by oxidative stress, and this enhanced signal decay is suppressed by giving radical scavengers, etc. By analyzing the enhancement of this attenuation in detail, it is possible to specify the type of radical or the location at which the free radicals are produced. Such non-invasive techniques to measure free radicals like the present in vivo ESR technique should provide considerable information for elucidating the mechanisms of diseases.View full abstractDownload PDF (8178K)
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