Song Meng-Ran, Huang Ming-Zhi, Tao Wei-Jie, Yong Zheng, Su Rui-Bin
Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Taiping Road 27, Beijing, 100850, China.
School of Pharmacy, Henan University, Kaifeng, 475004, China.
Sci Rep. 2025 Jan 3;15(1):653. doi: 10.1038/s41598-024-84440-x.
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 α and µ receptors. The effects of tandospirone (10 µM) on αβγ and αβδ 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 SaO 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) receptor antagonist WAY100635 (1 mg/kg) (P < 0.05). Co-administration of tandospirone with dexmedetomidine or fentanyl did not affect α or µ receptors activation. Tandospirone (10 µM) did not affect αβγ and αβδ GABA receptor modulation (P < 0.05). Overall, tandospirone ameliorated respiratory depression caused by anesthetics in rats through 5-HT receptor activation.
呼吸抑制是麻醉剂的一种副作用。使用特定拮抗剂或呼吸兴奋剂进行治疗可逆转由麻醉剂引起的呼吸抑制；然而，它们也会干扰麻醉剂的镇静作用。先前的研究表明，坦度螺酮可能改善呼吸抑制而不影响麻醉剂的镇静作用。因此，我们评估了坦度螺酮（0.1 - 8毫克/千克）是否能改善大鼠麻醉模型中的呼吸抑制。采用蛋白激酶A重新分布方法来确定坦度螺酮是否激活α和μ受体。通过双电极电压钳法探究了坦度螺酮（10微摩尔）对αβγ和αβδGABA受体电流调制的影响。预防性给予坦度螺酮可减轻大鼠由麻醉剂引起的呼吸抑制。坦度螺酮（0.1 - 8毫克/千克）可提高接受芬太尼（80微克/千克）或咪达唑仑（80毫克/千克）治疗的大鼠的血氧饱和度（P < 0.05）。5-羟色胺（5-HT）受体拮抗剂WAY100635（1毫克/千克）抑制了坦度螺酮预防呼吸抑制的能力（P < 0.05）。坦度螺酮与右美托咪定或芬太尼联合使用不影响α或μ受体的激活。坦度螺酮（10微摩尔）不影响αβγ和αβδGABA受体的调制（P < 0.05）。总体而言，坦度螺酮通过激活5-HT受体改善了大鼠由麻醉剂引起的呼吸抑制。
