Effect of acute and chronic cholinesterase inhibition on biogenic amines in rat brain.
The effects of five cholinesterase inhibitors on forebrain monoamine and their metabolite levels, and on forebrain and plasma cholinesterase (ChE) activity in rat were studied in acute and chronic conditions. Acute tetrahydroaminoacridine (THA) dosing caused lower brain (68%) and higher plasma (90%) ChE inhibition than the other drugs studied and increased levels of brain dihydroxyphenylacetic acid (DOPAC) (236%), homovanillic acid (HVA) (197%) and 5-hydroxyindoleacetic acid (5-HIAA) (130%). Acute physostigmine (PHY) administration caused a 215% increase in brain DOPAC content. Despite high brain ChE inhibition induced by metrifonate (MTF), dichlorvos (DDVP) or naled no changes in brain noradrenaline (NA), dopamine (DA) or serotonin (5-HT) occurred due to treatment with the study drugs in the acute study. In the chronic 10-day study THA or PHY caused no substantial ChE inhibition in brain when measured 18 hours after the last dose, whereas MTF induced 74% ChE inhibition. Long-term treatment with THA or MTF caused no changes in monoamine levels, but PHY treatment resulted in slightly increased 5-HT values. These results suggest that MTF, DDVP and naled seem to act solely by cholinergic mechanisms. However, the central neuropharmacological mechanism of action of THA and PHY may involve changes in cholinergic as well as dopaminergic and serotoninergic systems.
Soininen
H
H
Department of Psychiatry, Southern Illinois University School of Medicine, Springfield 62794-9230.
Unni
L
L
Shillcutt
S
S
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D002802:Cholinesterases / Q000097:blood / Q000378:metabolism; D004006:Dichlorvos / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004334:Drug Administration Schedule; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012701:Serotonin / Q000378:metabolism; D013619:Tacrine / Q000494:pharmacology; D014236:Trichlorfon / Q000494:pharmacology
D001679:Biogenic Amines; D002800:Cholinesterase Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D013619:Tacrine; D006897:Hydroxyindoleacetic Acid; D004006:Dichlorvos; D010830:Physostigmine; D014236:Trichlorfon; D002802:Cholinesterases; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid