1994 Fiscal Year Final Research Report Summary
Chemical and Pharmacological Studies on Cardiotonic and Sedative Effects of Musk
| Project/Area Number |
04557098
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
KIKUCHI Tohru Toyama Medical and Pharmaceutical University, Research Institute for Wakan-Yaku, Professor, 和漢薬研究所, 教授 (40025680)
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| Co-Investigator(Kenkyū-buntansha) |
TEZUKA Yasuhiro Toyama Medical and Pharmaceutical University, Research Institute for Wakan-Yaku,, 和漢薬研究所, 助手 (70236975)
KIMURA Ikuko Toyama Medical and Pharmaceutical University, Faculty of Pharmaceutical Sciences, 薬学部, 助教授 (70019131)
KIMURA Masayasu Toyama Medical and Pharmaceutical University, Faculty of Pharmaceutical Sciences, 薬学部, 教授 (60019099)
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| Project Period (FY) |
1992 – 1994
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| Keywords | Musk / Cardiotonic Effect / Musclide-A1 / Musclide-A2 / Musclide-B / Synthesis / Protein kinase C activation / Sedative Effect |
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| Research Abstract |
1.Chemical Study on Cardiotonic Effect of Musk
Asymmetric syntheses of the cardiotonic activators, musclides-A1, -A2, and-B,which were isolated from the water soluble fraction of the musk extract, were achieved from valine or leucine through carbon chain elongation by Witting reaction followed by conversion of functional groups. All stereoisomers of musclides were also sy nthesized according to the similar procedure. By comparing their spectral data with those of natural ones, the structures of musclide-A2 and musclide-B were revised.
2.Pharmacological Study on Cardiotonic Effect of Musk
Among the musclides obtained, (2R,5S) -musclide-A1 showed the most effective cardiotonic action (isoproterenol-potenciating activity). Also musclide-A1 showed an activation effect towards protein kinase C from guinea-pig ventricular muscle and rat ventricular muscle. the activation mechanism of musclide-A1 was similar to that of 1,2-diacylglycerol. It should be noted that musclide-A1 activates specifically the protein kinase C from ventricular muscle, but not that from brain.
3.Studies on Sedative Effect of Musk
The ether extract of musk showed a sedative effect. It was separated by a combination of silica gel column chromatography and praparative TLC procedures, and muscone, cholesterol, and dehydroepiandrosterone were identified.
Studies on musk from the breeded musk deer
Musk from the breeded musk deer was extracted with ether. GC and TLC study of the ether extract showed similar profiles to those of natural musk, but it showed a significant difference in the relative amounts of the constituents. The biological activity of the ether extract is now under examination.
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