In rat brain amoxapine enhances dopamine metabolism: pharmacokinetic variations of the effect.
When rats were given i.p. amoxapine, the drug was biotransformed to 7-hydroxyamoxapine, but not to 8-hydroxyamoxapine. The maximal concentrations of amoxapine and 7-hydroxyamoxapine in the serum and brain were found 30 min after the single injection, and the concentration of the former in the brain was higher than that of the latter. During the chronic treatment the concentration of amoxapine in the brain was much higher than that of 7-hydroxyamoxapine. A single administration of amoxapine increased the brain levels of dihydroxyphenylacetic acid and homovanillic acid. Their highest levels were observed 6 h after the injection. Repeated administration reduced the increases; chronic treatment caused tolerance to the enhancing effects on dopamine (DA) metabolism. Tolerance was observed in both striatum and hippocampus, but not in frontal cortex and hypothalamus. Single or chronic injection did not appear to change the level of DA in the brain. Amoxapine itself could be chiefly responsible for the enhancement of DA metabolism. In addition, the level of 3-methoxy-4-hydroxyphenylethyleneglycol in brain decreased transiently right after the injection of amoxapine, but the norepinephrine level did not seem to change following single or chronic administration of amoxapine.
Kobayashi
A
A
Department of Neuropsychiatry, Aichi Medical College, Japan.
Fujita
K
K
Nakazawa
K
K
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000657:Amoxapine / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004357:Drug Synergism; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D014644:Genetic Variation; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D015102:3,4-Dihydroxyphenylacetic Acid; D008734:Methoxyhydroxyphenylglycol; C041917:7-hydroxyamoxapine; D000657:Amoxapine; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid