Brain microdialysis in rats: a technique to reveal competition in vivo between endogenous dopamine and moclobemide, a RIMA antidepressant.
In this study, the effect of the interaction between the short-acting reserpine-like dopamine (DA) releaser Ro 4-1284 (1 mg/kg IP) and the reversible inhibitors of monoamine oxidase type A (MAO-A), moclobemide (Aurorix) and Ro 41-1049 (20 mg/kg IP, each), on the outflow of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) was investigated by rat transstriatal microdialysis. The injection of Ro 4-1284 after MAO-A inhibitors produced a marked increase of DA concentrations corresponding to a bell-shaped change in DOPAC outflow. This effect was more pronounced in rats treated with moclobemide than with Ro 41-1049. These data support the view that the increment of the endogenous substrate DA might displace moclobemide more rapidly than Ro 41-1049 from MAO-A active sites. The microdialysis method is proposed as a more reliable in vivo technique to investigate the degree of reversibility of the reversible MAO-A inhibitors.
Colzi
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A
Pharmaceutical Research Department (PRPN), F. Hoffmann-La Roche Ltd, Basel, Switzerland.
d'Agostini
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F
Cesura
A M
AM
Da Prada
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M
D012369:2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy- / Q000494:pharmacology; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D020912:Moclobemide; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013844:Thiazoles / Q000494:pharmacology
D001549:Benzamides; D008996:Monoamine Oxidase Inhibitors; D013844:Thiazoles; D015102:3,4-Dihydroxyphenylacetic Acid; D012369:2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy-; C063456:Ro 41-1049; D008995:Monoamine Oxidase; D020912:Moclobemide; D004298:Dopamine