Chronic administration of the antidepressant-antipanic drug phenelzine and its N-acetylated analogue: effects on monoamine oxidase, biogenic amines, and alpha 2-adrenoreceptor function.
Phenelzine (PLZ), a nonselective monoamine oxidase inhibitor, is widely used in psychiatry for the treatment of panic disorder and depression. The effects of chronic (28-day) administration of PLZ (0.05 mmol/kg/day) and its N-acetylated analogue, 1-acetyl-2-(2-phenylethyl) hydrazine (N2-acetylphenelzine; N2AcPLZ; 0.10 mmol/kg/day), on alpha 2-adrenoreceptor function were investigated by use of a behavioral test on days 21 and 22. Rats treated with PLZ or N2AcPLZ displayed a significant attenuation of the suppressant effects of clonidine on spontaneous locomotor activity, compared with controls; these results suggest a reduced sensitivity of alpha 2-adrenoreceptors. By day 28, both PLZ and N2AcPLZ had produced greater than 85% inhibition of monoamine oxidases A and B in the brain, heart, and liver. Both drugs induced significant elevations of whole-brain levels of noradrenaline, 5-hydroxytryptamine, and dopamine, compared with those in controls. The levels of acid metabolites of dopamine and 5-hydroxytryptamine (homovanillic acid, 3,4-dihydroxyphenylacetic acid, and 5-hydroxyindole-3-acetic acid) were significantly reduced in both groups of drug-treated animals.
McKenna
K F
KF
Department of Psychiatry, University of Alberta, Edmonton, Canada.
Baker
G B
GB
Coutts
R T
RT
Greenshaw
A J
AJ
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001679:Biogenic Amines / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008995:Monoamine Oxidase / Q000187:drug effects; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D016584:Panic Disorder / Q000188:drug therapy*; D010624:Phenelzine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012680:Sensitivity and Specificity; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors
D000928:Antidepressive Agents; D001679:Biogenic Amines; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D011942:Receptors, Adrenergic, alpha; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C043198:N-acetylphenelzine; D008995:Monoamine Oxidase; D003000:Clonidine; D010624:Phenelzine; D004298:Dopamine; D006719:Homovanillic Acid