Tandospirone Prevents Anesthetic-Induced Respiratory Depression through 5-HT1A Receptor Activation in Rats
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Background: Respiratory depression is a side effect of anesthetics such as fentanyl, dexmedetomidine, and midazolam. Clinical treatment with specific antagonists or respiratory stimulants interferes with the sedative effects of anesthetics; therefore, drugs that ameliorate respiratory depression without affecting the sedative effects of anesthetics are needed. Previous studies have suggested that tandospirone may be one such candidate. Therefore, we performed pharmacological studies in rats to evaluate this issue. Methods: The pharmacodynamic ability of tandospirone to ameliorate respiratory depression and its effects on arterial oxygen saturation (SaO 2 ) were evaluated in a rat model under anesthesia. The protein kinase A redistribution method was used to determine whether tandospirone activated α 2a/2c and μ receptors. The effects of tandospirone on current modulation of α 1 β 2 γ 2 and α 4 β 2 δ gamma amino-butyric acid (GABA) receptors were explored using the two-electrode voltage clamp technique. Results: Prophylactic administration of tandospirone reduced respiratory depression caused by fentanyl, dexmedetomidine, and midazolam in rats. Tandospirone increased SaO 2 in rats treated with fentanyl or midazolam. The ability of tandospirone to prevent respiratory depression was completely inhibited by the 5-hydroxytryptamine (5-HT) 1A receptor antagonist WAY100635. Co-administration of tandospirone with dexmedetomidine or fentanyl did not affect the activation of α 2a/2c or μ receptors by dexmedetomidine or fentanyl. Tandospirone did not affect the modulation of α 1 β 2 γ 2 and α 4 β 2 δ GABA receptors by midazolam. Conclusion: Tandospirone ameliorates respiratory depression caused by anesthetics in rats through 5-HT 1A receptor activation. Future studies should validate these findings and evaluate whether tandospirone has clinical application value for ameliorating respiratory depression in patients receiving anesthetics.
