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Mild hypothermia (ie, 34 C) may prove therapeutic for patients with stroke, but it usually provokes shivering. We tested the hypothesis that the combination of buspirone (a serotonin 1A partial agonist) and meperidine synergistically reduces the shivering threshold (triggering tympanic membrane temperature) to at least 34 C while producing little sedation or respiratory depression. Eight volunteers each participated on four randomly-assigned days: 1) large-dose oral buspirone (60 mg); 2) large-dose IV meperidine (target plasma concentration of 0.8 μg/mL); 3) the combination of buspirone (30 mg) and meperidine (0.4 μg/mL); and 4) a control day without drugs. Core hypothermia was induced by infusion of lactated Ringer’s solution at 4 C. The control shivering threshold was 35.7 C±0.2 C. The threshold was 35.0 C±0.8 C during large-dose buspirone and 33.4 C±0.3 C during large-dose meperidine. The threshold …