Lack of neuroprotective effect of sigma receptor ligands in the neurotoxicity of p-chloroamphetamine in rat brain.
We studied the mechanism of antagonism of p-chloroamphetamine-induced neurotoxicity by dextromethorphan. The pretreatment with potent and selective sigma receptor ligands, 4-phenyl-4-(1-phenylbutyl)piperidine (4-PPBP) and N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100), did not alter the reduction of 5-hydroxytryptamine and 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in the cerebral cortex by repeated administration of p-chloroamphetamine. These results suggest that sigma receptors might not play a significant role in the antagonism of p-chloroamphetamine-induced neurotoxicity by dextromethorphan.
Narita
N
N
Division of Cortical Function Disorder, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan.
Hashimoto
K
K
Iyo
M
M
Minabe
Y
Y
Yamazaki
K
K
D000818:Animals; D000840:Anisoles / Q000494:pharmacology; D000996:Antitussive Agents / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003915:Dextromethorphan / Q000494:pharmacology; D006220:Haloperidol / Q000031:analogs & derivatives / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008024:Ligands; D008297:Male; D011437:Propylamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000633:toxicity*; D010133:p-Chloroamphetamine / Q000037:antagonists & inhibitors / Q000633:toxicity*
D000840:Anisoles; D000996:Antitussive Agents; D008024:Ligands; D011437:Propylamines; D017480:Receptors, sigma; D018490:Serotonin Agents; C094850:4-phenyl-1-(4-phenylbutyl)piperidine; C083832:N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D010133:p-Chloroamphetamine; D003915:Dextromethorphan; D006220:Haloperidol