Prenatal effects of acute harmaline exposure on fetal brain biogenic amine metabolism.
Harmaline, a known type A monoamine oxidase (MAO) inhibitor in adult brain of various species was found to elevate whole brain levels of dopamine and serotonin (5-HT) in rat fetuses of mothers injected 2-4 h before Caesarean delivery. Similar stimulatory effects were observed for the norepinephrine metabolite 3-methoxy-4-hydroxy-phenylglycol (MHPG), however, no significant effect was obtained for norepinephrine. The dopamine metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) and the 5-HT metabolite 5-hydroxyindole acetic acid (5-HIAA) were decreased with the same treatment. These results imply that harmaline or one of its metabolites may cross the placental barrier to affect the fetal brain system not merely as a type A MAO inhibitor (i.e., relatively 5-HT-specific), but possibly also as a stimulatory agent for aldehyde reductase or catechol-O-methyltransferase (COMT) or alternately as an agent inhibiting the conjugation, efflux, or turnover of biogenic amine metabolites such as MHPG.
Okonmah
A D
AD
College of Pharmacy, Florida A & M University Clinical Research Unit, Miami.
Brown
J W
JW
Blyden
G T
GT
Soliman
K F
KF
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000470:Alkaloids / Q000633:toxicity*; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006246:Harmaline / Q000633:toxicity*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000470:Alkaloids; D001679:Biogenic Amines; D015102:3,4-Dihydroxyphenylacetic Acid; D006897:Hydroxyindoleacetic Acid; D006246:Harmaline; D002394:Catechol O-Methyltransferase; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid