Ketamine is an old drug with new clinical uses beyond anesthesia and pain relief, including treatment for asthma, epilepsy, depression, bipolar disorder, and addiction to alcohol and heroin. It works mainly as a noncompetitive blocker of the NMDA receptor, though its full mechanism is complex. Low doses and short-term use are generally safe and cause few side effects. However, ketamine is also a powerful psychostimulant and has become a commonly abused drug over the past decade.
Ketamine and a ketamine-magnesium sulfate combination lower body temperature in rats through serotonergic and adrenergic mechanisms, but not through GABAA receptors. Giving yohimbine, an α2-adrenergic blocker, deepened ketamine-induced hypothermia at doses of 0.5 and 1 mg/kg, while only the highest dose (3 mg/kg) enhanced the combination's effect. Methysergide, a serotonin blocker, had opposite effects depending on dose: 1 mg/kg worsened ketamine hypothermia, whereas 0.5 mg/kg reduced the combination's cooling effect. Bicuculline, a GABAA antagonist, did not change hypothermia from either treatment. These findings clarify neurotransmitter pathways involved in NMDA antagonist-related thermoregulation.