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J Pharmacol Sci. 2016 Oct;132(2):166-170. doi: 10.1016/j.jphs.2016.10.001. Epub 2016 Oct 8.

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

Author information

1
Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea.
2
Department of Anatomy, College of Medicine, Chung-Ang University, Seoul 06974, Republic of Korea.
3
Department of Neuroscience, College of Medicine, Korea University, Seoul 02841, Republic of Korea.
4
Department of Neurobiology, School of Medicine, Kangwon National University, Chunchon 24341, Republic of Korea.
5
Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 06974, Republic of Korea.
6
School of Veterinary Medicine, Kangwon National University, Chunchon 24341, Republic of Korea.
7
Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
8
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.
9
Advanced Diagnostic System Research Laboratory, Fujita Health University Graduate School of Health Science, Aichi 470-1192, Japan.
10
Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea. Electronic address: kimhc@kangwon.ac.kr.

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.

KEYWORDS:

Administration route; High-dose dextromethorphan; Myelinoid bodies with mitochondrial dysfunction

PMID:
27802908
DOI:
10.1016/j.jphs.2016.10.001
[Indexed for MEDLINE]
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