Renal protective effect of sinorphan, an enkephalinase inhibitor

脑啡肽酶抑制剂华诺芬的肾保护作用

• 批准号: 07457559
• 负责人: FUJIMURA Akio.MD.PhD.
• 金额: $ 3.2万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457559/
• 关键词: atrial natriuretic peptide; enkephalinase inhibitor; sinorphan; cyclosporine; renal protection; 免疫抑制薬; 腎障害

Nephrotoxixity is the most bothersome adverse effect of cyclosporine A (CyA), an immunosuppressive agent, and can result in irreversible renal damage. The agent is widely used for the treatment of patients with organ transplant. Therefore, it is important that the drug-induced nephrotoxicity be prevented.In these studies, the effects of sinorphan, an enkephalinase inhibitor, on CyA-induced adverse events including nephrotoxicity and its immunosuppressive action were examined.The following results were obtained ;1)Sinorphan protects against the CyA-induced renal damage.2)Sinorphan prevents the elevation of blood pressure, probably by inhibition of enhanced endothelin production by CyA.3)Sinorphan does not influence the imunosuppressive action fo CyA.4)Sinorphan does not alter the CyA concentration in blood.These results that sinorphan prevents the CyA-induced adverse events without changing the pharmacologic effecfts of CyA.

肾毒性是免疫抑制剂环孢素A（CyA）最令人烦恼的副作用，可导致不可逆的肾损伤。该药剂广泛用于治疗器官移植患者。因此，预防药物引起的肾毒性是很重要的。在这些研究中，检查了脑啡肽酶抑制剂sinorphan对CyA引起的不良事件（包括肾毒性）的影响及其免疫抑制作用。1）Sinorphan对CyA诱导的肾脏损害具有保护作用。2）Sinorphan可防止血压升高，Sinorphan对CyA的免疫抑制作用无影响。4）Sinorphan不改变CyA的血药浓度，表明Sinorphan能预防CyA引起的不良反应，而不改变CyA的药理作用。

项目成果

A.Fujimra, et al.: "Protection against aminoglycoside-induced nephrotoxicity by sinorphan, an enkephalinase inhibitor."

A.Fujimra 等人：“脑啡肽酶抑制剂华诺芬可防止氨基糖苷类诱导的肾毒性。”

Fujimura A: "Preventive effect of sinorphan, an enkephalinase inhibitor, on cyclosporin-induced nephrotoxicity." Can J Physiol Pharmcol. 72. 854 (1994)

Fujimura A：“sinorphan（一种脑啡肽酶抑制剂）对环孢菌素诱导的肾毒性的预防作用。”

Y Takede, et al.: "Prevention of cyclosporine-induced hypertension by chronic treatment with neutral endopeptidase inhibitor in rats."

Y Takede 等人：“通过对大鼠进行中性肽链内切酶抑制剂的长期治疗来预防环孢素诱发的高血压。”

Fujimura A: "Protedtion against aminoglycoside-induced nephrotoxicity by sinorphan, an enkephalinase inhibitor." J Pharmacol Exp Ther. (in press).

Fujimura A：“通过脑啡肽酶抑制剂华诺芬来预防氨基糖甙类药物引起的肾毒性。”

A.Fujimura, et al.: "Effect of sinorphan, an enkephalinase inhibitor, on amikacin-induced nephrotoxicity."

A.Fujimura 等人：“脑啡肽酶抑制剂华诺啡对阿米卡星诱导的肾毒性的影响”。