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Memantine, an NMDA antagonist, prevents the development of hyperthermia in an animal model for serotonin syndrome.
Pharmacopsychiatry 2004; 37(2):57-62P

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

Since memantine is clinically well tolerated, this drug is a particularly promising therapeutic drug for 5-HT syndrome treatment.

Authors+Show Affiliations

Department of Psychiatry, Jichi Medical School, Kawachi-Gun, Tochigi-Ken, 329-0498, Japan. psychiat@jichi.ac.jp

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15048612

Citation

Nisijima, K, et al. "Memantine, an NMDA Antagonist, Prevents the Development of Hyperthermia in an Animal Model for Serotonin Syndrome." Pharmacopsychiatry, vol. 37, no. 2, 2004, pp. 57-62.
Nisijima K, Shioda K, Yoshino T, et al. Memantine, an NMDA antagonist, prevents the development of hyperthermia in an animal model for serotonin syndrome. Pharmacopsychiatry. 2004;37(2):57-62.
Nisijima, K., Shioda, K., Yoshino, T., Takano, K., & Kato, S. (2004). Memantine, an NMDA antagonist, prevents the development of hyperthermia in an animal model for serotonin syndrome. Pharmacopsychiatry, 37(2), pp. 57-62.
Nisijima K, et al. Memantine, an NMDA Antagonist, Prevents the Development of Hyperthermia in an Animal Model for Serotonin Syndrome. Pharmacopsychiatry. 2004;37(2):57-62. PubMed PMID: 15048612.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Memantine, an NMDA antagonist, prevents the development of hyperthermia in an animal model for serotonin syndrome. AU - Nisijima,K, AU - Shioda,K, AU - Yoshino,T, AU - Takano,K, AU - Kato,S, PY - 2004/3/30/pubmed PY - 2004/8/3/medline PY - 2004/3/30/entrez SP - 57 EP - 62 JF - Pharmacopsychiatry JO - Pharmacopsychiatry VL - 37 IS - 2 N2 - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Since memantine is clinically well tolerated, this drug is a particularly promising therapeutic drug for 5-HT syndrome treatment. SN - 0176-3679 UR - https://www.unboundmedicine.com/medline/citation/15048612/Memantine_an_NMDA_antagonist_prevents_the_development_of_hyperthermia_in_an_animal_model_for_serotonin_syndrome_ L2 - http://www.thieme-connect.com/DOI/DOI?10.1055/s-2004-815526 DB - PRIME DP - Unbound Medicine ER -