セロトニン機能からみたうつ病の病態及び抗うつ薬の作用機序に関する研究

从5-羟色胺功能角度研究抑郁症病理及抗抑郁药作用机制

• 批准号: 06670974
• 负责人: 石郷岡 純
• 金额: $ 1.02万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670974/
• 关键词: 抗うつ薬; セロトニン; 血小板; 取り込み部位; 親和性

1.対象薬となる抗うつ薬としてduloxetineを選択し、正常被検者8人を用い血小板セロトニン(5HT)取り込み機構に対する効果を検討した。2.Duloxetine 20mgを朝1回、連続7日間服用後のin vitroの3H-5HT取り込み阻害パターンは競合阻害のまま変わりはなかった。3.同様に、連続7日間服用の前後で、in vitroにおける3H-5HT取り込み阻害、3H-paroxetin結合阻害のKm,Vmax値に変化はみられなかった。4.Duloxetine服用中のex vivoにおける3H-5HT取り込み阻害能は、duloxetineの血中濃度より推定される値より、常に数倍の高値を示していた。5.洗浄血小板浮遊液を用い、in vitroの3H-5HT取り込み阻害能に対する薬物洗浄の効果を補助実験として行ったが、duloxetine,paroxetineについてはその効果は認められなかったが、trazodoneでは認められた。6.Duloxetine 20mg連続7日間服用では、血小板膜上の5HT取り込み部位の変化はおこらないと考えられる。7.Ex vivoにおける5HT取り込み阻害能の持続的高値は、duloxetineの血中濃度が低下した後もその薬理効果が持続するためと考えられる。8.5HT取り込み部位に対する親和性の高いduloxetine,paroxetineでは薬物洗浄の効果はなく、親和性の低いtrazodoneでは効果があったことから、親和性の高い薬物ほど5HT取り込み部位に対する結合が持続しやすいことが示唆される。9.抗うつ薬の用法、用量を決定する際には、薬物動態だけでなく、標的作用部位への親和性も考慮に入れる必要があると考えられる。

1. For example, 8 normal recipients were selected for anti-duloxetine test, and 8 normal recipients were treated with platelet scavenging assay (5HT). After using the 2.Duloxetine 20mg for 7 days, in vitro the 3H-5HT to pick up the block and close the block to stop the damage. 3. The same treatment, 7 days of contact before and after medication, in vitro testing 3H-5HT to remove the damage, 3H-paroxetin combined to block the impact of Km,Vmax treatment to improve the quality of the drug. In the course of taking 4.Duloxetine, ex vivo was taken, 3H-5HT was taken, duloxetine was taken, the degree of blood was presumed to be high, and several times higher than normal. 5. The platelet floatation solution was used, the in vitro 3H-5HT was used to prevent the damage, the product was washed, the duloxetine,paroxetine was used, the platelet floatation solution was used, the platelet floatation solution was used, and trazodone was used. After 7 days of 6.Duloxetine 20mg connection, the drug was taken, and the 5HT was removed on the platelet membrane. The results of 7.Ex vivo 5HT test showed that the blood temperature of the patients was low, and that of the duloxetine patients was low. 8.5HT samples were collected from different parts and parts of the body. The results showed that there was no significant difference between the two groups. The results showed that there was no significant difference between the two groups. The results showed that there was no significant difference between the two groups (8.5HT). The results showed that there was no significant difference between the two groups. The results showed that there was no significant difference between the two groups. The results showed that there was no significant difference between the two groups. The results showed that there was no significant difference between the two parts of 8.5HT. 9. The usage and dosage of anti-drug determine whether it is necessary to determine the content of the drug, the content of the product, the site of action, and the sex test.