Does meperidine have a unique anti-shivering mechanism?
Finally, we return to the intriguing question: which pharmacological properties of meperidine mediate its anti-shivering action? Meperidine is the only member of the opioid family that has clinically important local anesthetic activity in the dose range normally used for analgesia and is unique among currently used opioids in being effective as a sole agent for spinal anesthesia (323). However, local anesthetic action does not appear to mediate the drug’s anti-shivering action in humans since a clinical dose of intravenous lidocaine does not prevent shivering (324) or reduce the shivering threshold (325). Analgesic concentrations of meperidine produce considerable inhibition of 5-HT reuptake (326). Meperidine, in combination with a MAO inhibitor, can consequently cause fatal hyperthermia that is presumably due to the accumulation of brain 5-HT (327). The 50% inhibitory concentration (IC50) of meperidine for 5-HT reuptake is 490 nM, but more than 100,000 for morphine (328). Moreover, me
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