Effects of chronic oral administration of L-deprenyl in the dog.
Dogs were administered capsules containing L-deprenyl daily over 3 weeks at dose levels of 0, 0.1, 0.5, and 1.0 mg/kg. Spontaneous behavior was measured using a canine open field test, and was not significantly affected by L-deprenyl. Plasma levels of amphetamine showed a clear dose-dependent elevation 2 h and was not significantly affected by L-deprenyl. Plasma levels of amphetamine showed a clear dose-dependent elevation 2 h following treatment, but were markedly lower after 24 h, and were undetectable 5 days following the last treatment. Plasma levels of phenylethylamine were increased, but were highly variable. Animals sacrificed 1 day following the last treatment showed a dose-dependent inhibition of monoamine oxidase B in the brain, liver, and kidney, whereas monoamine oxidase A was unaffected in these tissues. L-Deprenyl also caused an increase in phenylethylamine in the striatum and hypothalamus, but not in the neocortex. Brain levels of DA, DOPAC, 3-MT, HVA, 5-HT, and 5-HIAA were unaffected. The pharmacological profile for the dog is distinct from that of other species in that long-term treatment did not produce any significant inhibition of MAO-A activity. The absence of an effect on biogenic amines or metabolites suggests that the metabolism of dopamine is mediated at least in part through pathways other than MAO-B in the normal adult dog.
Milgram
N W
NW
Life Sciences Division, University of Toronto, Scarborough, Ontario, Canada.
Ivy
G O
GO
Murphy
M P
MP
Head
E
E
Wu
P H
PH
Ruehl
W W
WW
Yu
P H
PH
Durden
D A
DA
Davis
B A
BA
Boulton
A A
AA
D000661:Amphetamine / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D004285:Dogs; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008995:Monoamine Oxidase / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D010627:Phenethylamines / Q000097:blood / Q000493:pharmacokinetics; D012642:Selegiline / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism
D010627:Phenethylamines; D012642:Selegiline; D012701:Serotonin; D000661:Amphetamine; D008995:Monoamine Oxidase; D004298:Dopamine