Tandospirone prevents anesthetic-induced respiratory depression through 5-HT1A receptor activation in rats
Abstract Respiratory depression is a side effect of anesthetics. Treatment with specific antagonists or respiratory stimulants can reverse respiratory depression caused by anesthetics; however, they also interfere with the sedative effects of anesthetics. Previous studies have suggested that tandosp...
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Nature Portfolio
2025-01-01
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| author | Meng-ran Song Ming-zhi Huang Wei-jie Tao Zheng Yong Rui-bin Su |
| author_facet | Meng-ran Song Ming-zhi Huang Wei-jie Tao Zheng Yong Rui-bin Su |
| author_sort | Meng-ran Song |
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| description | Abstract Respiratory depression is a side effect of anesthetics. Treatment with specific antagonists or respiratory stimulants can reverse respiratory depression caused by anesthetics; however, they also interfere with the sedative effects of anesthetics. Previous studies have suggested that tandospirone may ameliorate respiratory depression without affecting the sedative effects of anesthetics. Therefore, we evaluated whether tandospirone (0.1–8 mg/kg) ameliorates respiratory depression in a rat model under anesthesia. The protein kinase A redistribution method was used to determine whether tandospirone activates α2a/2c and µ receptors. The effects of tandospirone (10 µM) on α1β2γ2 and α4β2δ GABA receptor current modulation were explored by two-electrode voltage clamping. Prophylactic tandospirone administration reduced respiratory depression caused by anesthetics in rats. Tandospirone (0.1–8 mg/kg) increased SaO2 in rats treated with fentanyl (80 µg/kg) or midazolam (80 mg/kg) (P < 0.05). The ability of tandospirone to prevent respiratory depression was inhibited by the 5-hydroxytryptamine (5-HT)1 A receptor antagonist WAY100635 (1 mg/kg) (P < 0.05). Co-administration of tandospirone with dexmedetomidine or fentanyl did not affect α2a/2c or µ receptors activation. Tandospirone (10 µM) did not affect α1β2γ2 and α4β2δ GABA receptor modulation (P < 0.05). Overall, tandospirone ameliorated respiratory depression caused by anesthetics in rats through 5-HT1A receptor activation. |
| format | Article |
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| institution | Kabale University |
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| spelling | doaj-art-f0beb24be6e34dea8876ba564ea029942025-01-05T12:22:33ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-024-84440-xTandospirone prevents anesthetic-induced respiratory depression through 5-HT1A receptor activation in ratsMeng-ran Song0Ming-zhi Huang1Wei-jie Tao2Zheng Yong3Rui-bin Su4Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and ToxicologyBeijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and ToxicologyBeijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and ToxicologyBeijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and ToxicologyBeijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and ToxicologyAbstract Respiratory depression is a side effect of anesthetics. Treatment with specific antagonists or respiratory stimulants can reverse respiratory depression caused by anesthetics; however, they also interfere with the sedative effects of anesthetics. Previous studies have suggested that tandospirone may ameliorate respiratory depression without affecting the sedative effects of anesthetics. Therefore, we evaluated whether tandospirone (0.1–8 mg/kg) ameliorates respiratory depression in a rat model under anesthesia. The protein kinase A redistribution method was used to determine whether tandospirone activates α2a/2c and µ receptors. The effects of tandospirone (10 µM) on α1β2γ2 and α4β2δ GABA receptor current modulation were explored by two-electrode voltage clamping. Prophylactic tandospirone administration reduced respiratory depression caused by anesthetics in rats. Tandospirone (0.1–8 mg/kg) increased SaO2 in rats treated with fentanyl (80 µg/kg) or midazolam (80 mg/kg) (P < 0.05). The ability of tandospirone to prevent respiratory depression was inhibited by the 5-hydroxytryptamine (5-HT)1 A receptor antagonist WAY100635 (1 mg/kg) (P < 0.05). Co-administration of tandospirone with dexmedetomidine or fentanyl did not affect α2a/2c or µ receptors activation. Tandospirone (10 µM) did not affect α1β2γ2 and α4β2δ GABA receptor modulation (P < 0.05). Overall, tandospirone ameliorated respiratory depression caused by anesthetics in rats through 5-HT1A receptor activation.https://doi.org/10.1038/s41598-024-84440-x5-HT1ATandospironeRespiratory depressionFentanylMidazolamDexmedetomidine |
| spellingShingle | Meng-ran Song Ming-zhi Huang Wei-jie Tao Zheng Yong Rui-bin Su Tandospirone prevents anesthetic-induced respiratory depression through 5-HT1A receptor activation in rats Scientific Reports 5-HT1A Tandospirone Respiratory depression Fentanyl Midazolam Dexmedetomidine |
| title | Tandospirone prevents anesthetic-induced respiratory depression through 5-HT1A receptor activation in rats |
| title_full | Tandospirone prevents anesthetic-induced respiratory depression through 5-HT1A receptor activation in rats |
| title_fullStr | Tandospirone prevents anesthetic-induced respiratory depression through 5-HT1A receptor activation in rats |
| title_full_unstemmed | Tandospirone prevents anesthetic-induced respiratory depression through 5-HT1A receptor activation in rats |
| title_short | Tandospirone prevents anesthetic-induced respiratory depression through 5-HT1A receptor activation in rats |
| title_sort | tandospirone prevents anesthetic induced respiratory depression through 5 ht1a receptor activation in rats |
| topic | 5-HT1A Tandospirone Respiratory depression Fentanyl Midazolam Dexmedetomidine |
| url | https://doi.org/10.1038/s41598-024-84440-x |
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