Monoamine oxidase-B inhibition: a comparison of in vivo and ex vivo measures of reversible effects.
A behavioural test involving potentiation of the effects of an acute injection of beta-phenylethylamine (10 mg kg-1 i.p.) was used to assess the time-course of type-B MAO inhibition after administration of (--)deprenyl (5 mg kg-1 i.p.) and of MD 240928 (20 mg kg-1 i.p.) respectively. Potentiation of the effects of beta-phenylethylamine was observed 1 h after injection of (-)deprenyl or MD 240928. This effect was still evident 120 h after administration of (-)deprenyl but not 24 h after administration of MD 240928. Comparisons of ex vivo estimates of MAO activity yielded a corresponding time-course for the recovery of this enzyme. The extent of MAO inhibition required for potentiation of the effects of beta-phenylethylamine was inferred from a comparison of the behavioural test results and the ex vivo MAO activity observed after (-)deprenyl administration. These comparisons indicate a significant underestimation of MD 240928-induced MAO inhibition using ex vivo measures. This underestimation is interpreted as evidence for dilution effects in the ex vivo assay of MAO inhibition. The potentiation of effects of beta-phenylethylamine under the present conditions is proposed as a useful and simple test for effects of reversible type-B MAO inhibitors.
Turkish
S
S
Neuropsychiatric Research Unit, University of Saskatchewan, Saskatoon.
Yu
P H
PH
Greenshaw
A J
AJ
D000818:Animals; D004347:Drug Interactions; D066298:In Vitro Techniques; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects*; D010080:Oxazoles / Q000494:pharmacology*; D023303:Oxazolidinones; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012642:Selegiline / Q000494:pharmacology*; D013997:Time Factors
D010080:Oxazoles; D023303:Oxazolidinones; D010627:Phenethylamines; D012642:Selegiline; C029261:phenethylamine; C037871:MD 780236; D008995:Monoamine Oxidase