High-dose dextromethorphan produces myelinoid bodies in the hippocampus of rats.

Abstract

Dextromethorphan (DM) administered at supra-antitussive doses produce psychotoxic and neurotoxic effects in humans. We administered DM (80 mg/kg) to rats intraperitoneally to determine the ultrastructural change induced by DM, because intraperitoneal route is sensitive for the behavioral responses. Treatment with DM resulted in mitochondrial dysfunction and formation of myelinoid bodies in the hippocampus. MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate] attenuated DM-induced cytosolic oxidative burdens. However, neither MK-801 nor naloxone affected DM-induced mitochondrial dysfunction and formation of myelinoid bodies, indicating that the neurotoxic mechanism needs to be further elucidated. Therefore, the spectrum of toxicological effects associated with DM need to be reassessed.

• Authors: Hai-Quyen Tran, Yoon Hee Chung, Eun-Joo Shin, Won Ki Kim, Jae-Chul Lee, Ji Hoon Jeong, Myung Bok Wie, Choon-Gon Jang, Kiyofumi Yamada, Toshitaka Nabeshima, Hyoung-Chun Kim
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 132 Issue 2 Pg. 166-170 (Oct 2016) ISSN: 1347-8648 [Electronic] Japan
• PMID: 27802908 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Chemical References

• Antitussive Agents
• Dextromethorphan

Topics

• Animals
• Antitussive Agents (administration & dosage, toxicity)
• Cytosol (drug effects, pathology, ultrastructure)
• Dextromethorphan (administration & dosage, toxicity)
• Hippocampus (drug effects, pathology, ultrastructure)
• Injections, Intraperitoneal
• Mitochondria (drug effects, pathology, ultrastructure)
• Myelin Sheath (pathology, ultrastructure)
• Rats