High-dose dextromethorphan produces myelinoid bodies in the hippocampus of rats.
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.
Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea.
Hai-Quyen
HQ
Tran
Department of Anatomy, College of Medicine, Chung-Ang University, Seoul 06974, Republic of Korea.
Yoon Hee
YH
Chung
Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea.
Eun-Joo
EJ
Shin
Department of Neuroscience, College of Medicine, Korea University, Seoul 02841, Republic of Korea.
Won Ki
WK
Kim
Department of Neurobiology, School of Medicine, Kangwon National University, Chunchon 24341, Republic of Korea.
Jae-Chul
JC
Lee
Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 06974, Republic of Korea.
Ji Hoon
JH
Jeong
School of Veterinary Medicine, Kangwon National University, Chunchon 24341, Republic of Korea.
Myung Bok
MB
Wie
Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
Choon-Gon
CG
Jang
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.
Kiyofumi
K
Yamada
Advanced Diagnostic System Research Laboratory, Fujita Health University Graduate School of Health Science, Aichi 470-1192, Japan.
Toshitaka
T
Nabeshima
Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea. Electronic address: kimhc@kangwon.ac.kr.
Hyoung-Chun
HC
Kim
D000818:Animals; D000996:Antitussive Agents / Q000008:administration & dosage / Q000633:toxicity*; D003600:Cytosol / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D003915:Dextromethorphan / Q000008:administration & dosage / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure*; D007274:Injections, Intraperitoneal; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D009186:Myelin Sheath / Q000473:pathology / Q000648:ultrastructure*; D051381:Rats
D000996:Antitussive Agents; D003915:Dextromethorphan
Administration route; High-dose dextromethorphan; Myelinoid bodies with mitochondrial dysfunction