Article(id=1308455896300942299, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1308455539181114200, articleNumber=null, orderNo=null, doi=10.16438/j.0513-4870.2025-0496, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1745856000000, receivedDateStr=2025-04-29, revisedDate=1747584000000, revisedDateStr=2025-05-19, acceptedDate=null, acceptedDateStr=null, onlineDate=1789889795613, onlineDateStr=2026-09-20, pubDate=1752249600000, pubDateStr=2025-07-12, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1789889795613, onlineIssueDateStr=2026-09-20, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1789889795613, creator=13701087609, updateTime=1789889795613, updator=13701087609, issue=Issue{id=1308455539181114200, tenantId=1146029695717560320, journalId=1189982191388893191, year='2025', volume='60', issue='7', pageStart='1965', pageEnd='2374', issueExtLink='null', onlineDate='null', pubDate='1752249600000', pubDateStr='2025-07-12', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1789889710469, creator='13701087609', updateTime=1789895523604, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1308479921307807825, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1308455539181114200, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1308479921307807826, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1308455539181114200, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=2237, endPage=2245, ext={EN=ArticleExt(id=1308455896506463196, articleId=1308455896300942299, tenantId=1146029695717560320, journalId=1189982191388893191, language=EN, title=Tandospirone ameliorates fentanyl-induced respiratory depression and potentiates analgesic and sedative effects, columnId=1190335348761793317, journalTitle=Acta Pharmaceutica Sinica, columnName=Original Articles, runingTitle=null, highlight=null, articleAbstract=

To evaluate the effect of tandospirone (TS) on fentanyl (FEN)-induced respiratory depression and its impact on fentanyl's analgesic and sedative effects, a rat model of respiratory depression was established using FEN. After drug administration, respiratory frequency (F), tidal volume (TV), expiratory volume (EV), and enhanced pause (PENH) were measured using plethysmography. Blood oxygen saturation (SaO₂) was measured using a non-invasive pulse meter. The acetic acid writhing test, hot-plate test, and spontaneous activity test were used to evaluate the number of writhes, reaction time, and locomotor activity in mice. The righting reflex test was used to measure the loss rate and immobility time in rats [this experiment was approved by the Institute of Military Medicine Experimental Animal Management and Utilization Committee (approval number: IACUC-2023-001C)]. Compared with the respiratory depression model group (FEN 160 μg·kg^-1), the changes of F, TV, EV, PENH, SaO₂ in rats at the same time points after pre-treatment and treatment of different doses of TS were improved. TS (2 mg·kg^-1) and TS+FEN groups reduced the number of writhing movements, total distance of spontaneous activity and increased the maximmal possible effect (MPE), indicating that TS has its own analgesic and sedative effect and enhances the analgesic and sedative effect of FEN. The increase in the median effective concentration (EC₅₀) of loss of the righting reflex (LORR) and the reduction in immobilization time confirm that preconditioning with TS has a protective effect against FEN poisoning. In conclusion, TS ameliorates FEN-induced respiratory depression, and it possesses inherent sedative and analgesic effects. When co-administered with FEN, TS can enhance the analgesic and sedative effects of FEN. TS could serve as a non-opioid medication to improve opioid-induced respiratory depression and warrants further development and research.

, authors=Ming-zhi HUANG^{1, 2}, Zheng YONG^{2, *}, Rui-bin SU^{1, 2, *}, authorsList=Ming-zhi HUANG, Zheng YONG, Rui-bin SU, authorCompany=null, correspAuthors=Zheng YONG, Rui-bin SU, authorNote=null, correspAuthorsNote=null, copyrightStatement=Copyright ©2025 Acta Pharmaceutica Sinica. All rights reserved., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1308455899673162735, articleId=1308455896300942299, tenantId=1146029695717560320, journalId=1189982191388893191, language=CN, title=坦度螺酮改善芬太尼致呼吸抑制并增强镇痛镇静作用的研究, columnId=1190335348896011050, journalTitle=药学学报, columnName=研究论文, runingTitle=null, highlight=null, articleAbstract=

评价坦度螺酮(tandospirone, TS) 对芬太尼(fentanyl, FEN) 致呼吸抑制的改善作用及对其镇痛镇静效应影响。以芬太尼建立大鼠呼吸抑制模型, 检测呼吸频率(respiratory frequency, F)、潮气量(tidal volume, TV)、呼气量(expired volume, EV)、气道阻力(enhanced pause, PENH) 与检测血氧饱和度(oxygen saturation, SaO₂); 选择醋酸扭体、热板和自发活动模型检测小鼠扭体次数、反应时间及运动距离; 翻正反射实验检测大鼠消失率及制动时间(本实验获得军事医学研究院实验动物管理与使用委员会批准, 批准号: IACUC-2023-001C)。结果显示与呼吸抑制模型组比较, 坦度螺酮预防及治疗给药显著改善F值、TV值、EV值、PENH值变化幅度与SaO₂的降低, 表明TS改善FEN致呼吸抑制。TS单用及与FEN联用后显著减少扭体次数与运动总距离, 增加最大镇痛百分率(maximmal possible effect, MPE), 表明TS本身镇痛镇静并增加FEN的镇痛镇静作用; 翻正反射消失半数有效量(median effect concentration, EC₅₀) 增加和制动时间减少, 进一步证实TS预处理对FEN中毒具有较明显的保护效应。以上结论表明, 坦度螺酮能有效改善芬太尼所致呼吸抑制, 其本身具有镇静镇痛作用, 与芬太尼联用可以增强芬太尼的镇痛镇静作用, 作为非阿片类药物改善阿片类药物致呼吸抑制值得进一步开发研究。

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Exp Dermatol, 2022, 31: 600-607., articleTitle=null, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1308498302702813768, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, xref=1, ext=[AuthorCompanyExt(id=1308498302715396681, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, companyId=1308498302702813768, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=¹Nanjing University of Chinese Medicine, Nanjing 210023, China), AuthorCompanyExt(id=1308498302723785290, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, companyId=1308498302702813768, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=¹南京中医药大学, 江苏 南京 210023)]), AuthorCompany(id=1308498302828642891, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, xref=2, ext=[AuthorCompanyExt(id=1308498302837031500, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, companyId=1308498302828642891, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=²Academy of Military Medical Sciences, Beijing 100850, China), AuthorCompanyExt(id=1308498302841225805, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, companyId=1308498302828642891, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=²军事医学研究院, 北京 100850)])], figs=[ArticleFig(id=1308498307148776042, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, language=EN, label=null, caption=null, figureFileSmall=Mbl2gUhyoJVZMaDWyXDo0g==, figureFileBig=R7BglYLQREiQq+x4E0hW4Q==, tableContent=null), ArticleFig(id=1308498307438183019, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, language=CN, label=Fig.1, caption=Pre-treatment with TS attenuates FEN-induced respiratory depression with WBP recordings in rats. A-D: Effect of TS on F/TV/EV/PENH of FEN-induced respiratory depression. The F/TV/EV/PENH of each rat was measured for 20 minutes as baseline, the rats were administered intravenous TS (0.5, 1.0, 2.0 or 4.0 mg·kg^-1) and monitored continuously for 60 min after FEN injection (160 µg·kg^-1). n = 5, $ \stackrel{-}{x} $ ± s. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001 vs FEN group. TS: Tandospirone; FEN: Fentanyl; WBP: Whole-body plethysmographic; F: Respiratory frequency; TV: Tidal volume; EV: Expired volume; PENH: Enhanced pause, figureFileSmall=Mbl2gUhyoJVZMaDWyXDo0g==, figureFileBig=R7BglYLQREiQq+x4E0hW4Q==, tableContent=null), ArticleFig(id=1308498309082350188, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, language=EN, label=null, caption=null, figureFileSmall=K0ds42aMBELn/pGGwiTiDA==, figureFileBig=NUmB3foaAVULryi3PbkvKQ==, tableContent=null), ArticleFig(id=1308498309145264749, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, language=CN, label=Fig.2, caption=Treatment with TS attenuates FEN-induced respiratory depression with WBP recordings in rats. A-D: Effect of TS on F/TV/EV/PENH of FEN-induced respiratory depression. The F/TV/EV/PENH of each rat was measured for 20 minutes as baseline, the rats were administered intravenous FEN (160 µg·kg^-1) and monitored continuously for 60 min after TS (0.5, 1.0, 2.0 or 4.0 mg·kg^-1). n = 5, $ \stackrel{-}{x} $ ± s. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001 vs FEN group, figureFileSmall=K0ds42aMBELn/pGGwiTiDA==, figureFileBig=NUmB3foaAVULryi3PbkvKQ==, tableContent=null), ArticleFig(id=1308498309216567918, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, language=EN, label=null, caption=null, figureFileSmall=imh5U8l1oxSLJknOKV+bWg==, figureFileBig=Rm14gva9f0q5cqZ7KmM3wQ==, tableContent=null), ArticleFig(id=1308498309279482479, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, language=CN, label=Fig.3, caption=Pharmacodynamic ability of TS to ameliorate FEN-induced respiratory depression. Pre-treatment with TS attenuated the FEN-induced reduction of SaO₂ in rats. A: The rats were administered intravenous TS (0.5, 1.0, 2.0 or 4.0 mg·kg^-1) and monitored continuously for 60 min at 5-minute intervals after FEN (80 µg·kg^-1); B: The area under the curve for each experimental group. n = 6, $ \stackrel{-}{x} $ ± s. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001, ^****P < 0.000 1. SaO₂: Oxygen saturation, figureFileSmall=imh5U8l1oxSLJknOKV+bWg==, figureFileBig=Rm14gva9f0q5cqZ7KmM3wQ==, tableContent=null), ArticleFig(id=1308498309367562864, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, language=EN, label=null, caption=null, figureFileSmall=0F8NIow54uykUDrCQJkYvA==, figureFileBig=8mf7bdNKS0R2k1uVDeq7ZQ==, tableContent=null), ArticleFig(id=1308498309434671729, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, language=CN, label=Fig.4, caption=Pharmacodynamic ability of TS to ameliorate FEN-induced respiratory depression. Treatment with TS attenuated the FEN-induced reduction of SaO₂ in rats. A: The rats were administered intravenous FEN (80 µg·kg^-1) and monitored continuously for 60 min at 5-minute intervals after TS (0.5, 1.0, 2.0 or 4.0 mg·kg^-1); B: The area under the curve for each experimental group. n = 6, $ \stackrel{-}{x} $ ± s. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001, ^****P < 0.000 1, figureFileSmall=0F8NIow54uykUDrCQJkYvA==, figureFileBig=8mf7bdNKS0R2k1uVDeq7ZQ==, tableContent=null), ArticleFig(id=1308498309535335026, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, language=EN, label=null, caption=null, figureFileSmall=BrqI6IhU4xyR2ZnFJQNDhQ==, figureFileBig=t4naf5YMnXi95HrN9dNJ4A==, tableContent=null), ArticleFig(id=1308498309598249587, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, language=CN, label=Fig.5, caption=Comparison of the effects of TS (2.0 mg·kg^-1) and FEN (5, 10, 15 μg·kg^-1) on the acetic acid-induced nociceptive responses in the acetic acid-induced-writhing test as assessed by its extended 15-minute behavioural evaluation. A-C: The data obtained from the evaluation of the effects of administration on the writhing test following 0.6% acetic acid; D: The inhibition rates for each group. TS (2.0 mg·kg^-1) and FEN (5, 10, 15 μg·kg^-1) each reduced the number of twists. Pre-treatment with TS (2.0 mg·kg^-1) enhanced the FEN-induced reduction of the number of twists in mice. n = 10, $ \stackrel{-}{x} $ ± s. ^*P < 0.05, ^**P < 0.01, ^****P < 0.000 1, figureFileSmall=BrqI6IhU4xyR2ZnFJQNDhQ==, figureFileBig=t4naf5YMnXi95HrN9dNJ4A==, tableContent=null), ArticleFig(id=1308498309665358452, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, language=EN, label=null, caption=null, figureFileSmall=0c6vl4uNZVZSNzl/bZ2IIA==, figureFileBig=EOrx5WFGARLqcOEkYyhh7g==, tableContent=null), ArticleFig(id=1308498309724078709, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, language=CN, label=Fig.6, caption=The analgesic effects of TS (2.0 mg·kg^-1), FEN, and TS + FEN in the hot-plate test. A: The reaction times before and after drug administration; B: The MPE (%) for each group. n = 10, $ \stackrel{-}{x} $ ± s. ^*P < 0.05, ^**P < 0.01. MPE: Maximmal possible effect, figureFileSmall=0c6vl4uNZVZSNzl/bZ2IIA==, figureFileBig=EOrx5WFGARLqcOEkYyhh7g==, tableContent=null), ArticleFig(id=1308498309791187574, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, language=EN, label=null, caption=null, figureFileSmall=tJ90VyQoK1AzIR58h/zTeQ==, figureFileBig=iQIoQJ7AC63GRB7vdgCTMA==, tableContent=null), ArticleFig(id=1308498309862490743, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, language=CN, label=Fig.7, caption=Comparison of the effects of TS (2.0 mg·kg^-1) and FEN (5, 10, 15 μg·kg^-1) on spontaneous activity by its extended 60-minute behavioural evaluation. A-C: The total distance traveled by mice under different dosing conditions in the spontaneous activity test. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001, ^****P < 0.000 1; D: The time-sharing distance of each dose experimental group. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001, ^****P < 0.000 1 vs vehicle group. FEN (10, 15 μg·kg^-1) reduced the total distance (B, C). Pre-treatment with TS (2.0 mg·kg^-1) enhanced the FEN-induced reduction of the total distance in mice. n = 10, $ \stackrel{-}{x} $ ± s, figureFileSmall=tJ90VyQoK1AzIR58h/zTeQ==, figureFileBig=iQIoQJ7AC63GRB7vdgCTMA==, tableContent=null), ArticleFig(id=1308498309921211000, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, language=EN, label=null, caption=null, figureFileSmall=Ge7zGvUcBGHkSiGmLURogQ==, figureFileBig=1sx5l0JwY7mnoxHPtxYBOw==, tableContent=null), ArticleFig(id=1308498309979931257, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, language=CN, label=Fig.8, caption=Examples of movement trajectories for groups, figureFileSmall=Ge7zGvUcBGHkSiGmLURogQ==, figureFileBig=1sx5l0JwY7mnoxHPtxYBOw==, tableContent=null), ArticleFig(id=1308498310034457210, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, language=EN, label=null, caption=null, figureFileSmall=6jITjYRMdAkfmeeZ/i4U2A==, figureFileBig=soWXw26LFh+YhwkduCFKgA==, tableContent=null), ArticleFig(id=1308498310093177467, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308455896300942299, language=CN, label=Fig.9, caption=Comparison of the effects of TS and FEN on the disappearance rate and immobility time of the LORR. A: The disappearance rate of FEN group (10.0, 12.5, 15.0, 17.5 and 20.0 μg·kg^-1); B: The curve of nonlinear fitting for the disappearance rate of the FEN group; C: The disappearance rate of TS+FEN group (12.5, 15.0, 17.5, 20.0 and 25.0 μg·kg^-1); D: The curve of nonlinear fitting of FEN dosage after TS pretreatment; E: The immobility time following the LORR for FEN (80.0 μg·kg^-1) and TS (2.0 mg·kg^-1) + FEN. n = 5, $ \stackrel{-}{x} $ ± s. ^*P < 0.05. 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