Nisijima K, Shioda K, Yoshino T, Takano K, Kato S
Department of Psychiatry, Jichi Medical School, Kawachi-Gun, Tochigi-Ken, 329-0498, Japan.
Pharmacopsychiatry. 2004 Mar;37(2):57-62. doi: 10.1055/s-2004-815526.
Serotonin (5-HT) syndrome is the most serious side effect of antidepressants. Although several drugs have been used for the treatment of 5-HT syndrome, a universal pharmacotherapy has not been established. NMDA receptor antagonists have been reported to have neuroprotective effects. In the present study, the efficacy of NMDA antagonists, including memantine and MK-801, and potent 5-HT (2A) antagonists, including risperidone and ketanserin, was evaluated in a 5-HT syndrome animal model.
5-Hydroxy-l-tryptophan (100 mg/kg) and clorgyline (2 mg/kg) were administered intraperitoneally in rats to induce 5-HT syndrome. The rectal temperature of the rats was measured, and the noradrenaline (NA) and 5-HT levels in the anterior hypothalamus were measured using a microdialysis technique.
In the group pretreated with saline, the rectal temperature increased to more than 40 degrees C, and all of the animals died within 90 min of the drug's administration. The NA and 5-HT levels in the anterior hypothalamus increased to about 15- and 1100-fold of the pre-administration levels, respectively. Pretreatment with risperidone (0.5 mg/kg) and ketanserin (5 mg/kg) prevented the development of hyperthermia and the increase in the NA level. Memantine (10 mg/kg) and MK-801 (0.5 mg/kg) also prevented the development of hyperthermia and the increase in the NA level. These results suggest that NMDA antagonists, as well as potent 5-HT (2A) antagonists, may be effective drugs for the treatment of 5-HT syndrome.
Since memantine is clinically well tolerated, this drug is a particularly promising therapeutic drug for 5-HT syndrome treatment.
血清素（5-羟色胺，5-HT）综合征是抗抑郁药最严重的副作用。尽管已有多种药物用于治疗5-HT综合征，但尚未确立通用的药物疗法。据报道，N-甲基-D-天冬氨酸（NMDA）受体拮抗剂具有神经保护作用。在本研究中，在5-HT综合征动物模型中评估了包括美金刚和MK-801在内的NMDA拮抗剂以及包括利培酮和酮色林在内的强效5-HT（2A）拮抗剂的疗效。
给大鼠腹腔注射5-羟色氨酸（100mg/kg）和氯吉兰（2mg/kg）以诱导5-HT综合征。测量大鼠的直肠温度，并使用微透析技术测量下丘脑前部的去甲肾上腺素（NA）和5-HT水平。
在生理盐水预处理组中，直肠温度升至40摄氏度以上，所有动物在给药后90分钟内死亡。下丘脑前部的NA和5-HT水平分别升至给药前水平的约15倍和1100倍。利培酮（0.5mg/kg）和酮色林（5mg/kg）预处理可防止体温过高的发展和NA水平的升高。美金刚（10mg/kg）和MK-801（0.5mg/kg）也可防止体温过高的发展和NA水平的升高。这些结果表明，NMDA拮抗剂以及强效5-HT（2A）拮抗剂可能是治疗5-HT综合征的有效药物。
由于美金刚在临床上耐受性良好，该药是治疗5-HT综合征特别有前景的治疗药物。
