Neuropsychotoxicity of abused drugs: potential of dextromethorphan and novel neuroprotective analogs of dextromethorphan with improved safety profiles in terms of abuse and neuroprotective effects.
Drug abuse involving dextromethorphan, an antitussive, has been a social problem in various geographic locations since the 1960s. Ironically, high doses of the drug confer neuroprotective activity with central nervous system and behavioral effects. Accumulating evidence suggests that metabolism to phencyclidine-like dextrorphan is not essential for the neuroprotective activity of dextromethorphan. Here, we review the neuroprotective properties of dextromethorphan and its potential for abuse and the potential neuroprotective effects of the drug's analogs and 3-hydroxymorphinan, a metabolite of dextromethorphan. These compounds may provide a novel therapeutic direction for the treatment of neurodegenerative diseases such as convulsive or parkinsonian-like disorders.
Shin
Eun-Joo
EJ
Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, Korea.
Lee
Phil Ho
PH
Kim
Hyun Ji
HJ
Nabeshima
Toshitaka
T
Kim
Hyoung-Chun
HC
D000818:Animals; D000996:Antitussive Agents / Q000009:adverse effects / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D002545:Brain Ischemia / Q000188:drug therapy; D002490:Central Nervous System / Q000187:drug effects*; D003915:Dextromethorphan / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy; D012640:Seizures / Q000188:drug therapy; D013329:Structure-Activity Relationship; D019966:Substance-Related Disorders / Q000517:prevention & control*
D000996:Antitussive Agents; D018696:Neuroprotective Agents; D003915:Dextromethorphan; C054116:norlevorphanol