Effects of DM-9384, a pyrrolidone derivative, on ischemia-induced changes in the central monoamine systems.
Alterations in brain tissue levels of monoamines and monoamine metabolites were studied in gerbils 60 min after cerebral ischemia induced by 10 min carotid ligation after pretreatment with the antiischemic drug DM-9384 (1, 3, 10, 30 mg/kg, PO). The DA levels decreased in striatum after the ischemia, while cortical and hippocampal DA levels increased. The DOPAC levels increased in cortex, but were essentially unaffected in other regions. The HVA levels increased in all forebrain regions studied. NA levels decreased in hippocampus and superior colliculus, while a general increase in MHPG levels was seen. Decreases in 5-HT levels were seen in all forebrain regions except cortex. The 10 mg/kg and 30 mg/kg doses of DM-9384 counteracted the decrease in striatal 5-HT and hypothalamic MHPG/NA ratio, respectively. Thus pretreatment with DM-9384 exerted minor protective effects on the alterations induced in monoamine systems by transient forebrain ischemia.
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
J
J
Luthman
E
E
Lindqvist
E
E
Dell'Anna
H
H
Kojima
T
T
Shiotani
H
H
Tachizawa
L
L
Olson
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D002545:Brain Ischemia / Q000378:metabolism*; D002491:Central Nervous System Agents / Q000494:pharmacology*; D005849:Gerbillinae; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism
D015306:Biogenic Monoamines; D002491:Central Nervous System Agents; D011760:Pyrrolidinones; D015102:3,4-Dihydroxyphenylacetic Acid; C058876:nefiracetam; D012701:Serotonin; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D006719:Homovanillic Acid