The neuropharmacological profile of N-methyl-N-propargyl-2-aminotetralin: a potent monoamine oxidase inhibitor.
N-methyl-N-propargyl-2-aminotetralin (N-0425), a semi rigid analogue of deprenyl was found to be a potent inhibitor of monoamine oxidase type-A and -B. The MAO inhibitory potency was determined in in-vitro, ex-vivo and in-vivo experiments for racemic N-0425 and for both enantiomers, and compared with deprenyl. Racemic N-0425 and (-)N-0425 were found to inactivate both MAO-A and -B to about the same extent in rat brain homogenates, whereas (+)N-0425 was 10 times more potent in inhibiting MAO-B than MAO-A under in-vitro conditions. The latter compound was almost 3 times less active than (-)deprenyl with respect to inactivation of MAO-B. In ex-vivo experiments it was shown that (+/-)- and (+)N-0425 inhibited rat striatal MAO-B activity almost completely 2 h after a dose of 0.01 mmol/kg ip, whereas both compounds produced a much less rapid inactivation of type-A MAO, which was about 65% after 23 h. No potentiation of the tyramine induced increase in systolic blood pressure was found in normotensive rats following doses up to 0.01 mmol/kg ip of racemic N-0425, but a potentiation was observed after a higher dose of 0.04 mmol/kg. Levels of dopamine and noradrenaline were both increased in rat frontal cortex after the administration of N-0425, which can be interpreted as a reflection of MAO inactivation.(ABSTRACT TRUNCATED AT 250 WORDS)
Hazelhoff
B
B
De Vries
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JB
Dijkstra
D
D
de Jong
W
W
Horn
A S
AS
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D003010:Clorgyline / Q000494:pharmacology; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D009647:Normetanephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014439:Tyramine / Q000494:pharmacology
D001679:Biogenic Amines; D008996:Monoamine Oxidase Inhibitors; D009281:Naphthalenes; D013764:Tetrahydronaphthalenes; D009647:Normetanephrine; D015102:3,4-Dihydroxyphenylacetic Acid; D006897:Hydroxyindoleacetic Acid; C046824:N-methyl-N-propargyl-2-aminotetralin; D003010:Clorgyline; D009638:Norepinephrine; D006719:Homovanillic Acid; D014439:Tyramine