[Effects of 4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (MCI-2016) on monamine metabolism in the brain].
Effects of MCI-2016 on the uptake, contents and turnover rate of monoamines were studied in the rat brain. MCI-2016 exhibited more potent inhibitory effect on the noradrenaline (NA) uptake than on dopamine (DA) and serotonin (5-HT) uptake. Especially, the inhibitory effect of MCI-2016 on the NA uptake in the hypothalamus was comparable to that of imipramine with the IC50 value of 4 X 10(-8) M. The levels of NA and its metabolite, MHPG-SO4, in the whole brain were significantly increased by 30 mg/kg, i.p. of MCI-2016. The peak effects were reached between two to 4 hrs after administration. The increase in 5-HT contents at the cortex were also observed by MCI-2016 (30 mg/kg, i.p.), with little changes in 5-HIAA contents. The levels of DA, HVA and DOPAC in the whole brain were not significantly influenced by MCI-2016. The turnover rate of NA was facilitated by 61.1% by 15 mg/kg, i.p. of MCI-2016. DA and 5-HT turnover rates were little affected by the same dosage of MCI-2016. In the case of imipramine (15 mg/kg, i.p.), however, it didn't increase the NA turnover, and in addition, it inhibited the 5-HT turnover. The increase in NA turnover rate induced by MCI-2016 was antagonized by 54.5% by 30 mg/kg, i.p. of atropine. Physostigmine (1 mg/kg, i.p.) also increased NA turnover rate which was also partially (62.6%) inhibited by atropine. These results may suggest that the effects of MCI-2016 on noradrenergic mechanisms were qualitatively different from those of tricyclic antidepressants. In addition, the results with atropine on the turnover rate may in part suggest a possible participation of the cholinergic mechanism on the turnover increasing effect of MCI-2016.
D000818:Animals; D000928:Antidepressive Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D001559:Benzhydryl Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D009638:Norepinephrine / Q000378:metabolism*; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism
D000928:Antidepressive Agents; D001559:Benzhydryl Compounds; D012701:Serotonin; D001285:Atropine; D010830:Physostigmine; D004298:Dopamine; D009638:Norepinephrine; C031906:bifemelane