A major metabolite of bupropion reverses motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets

TY - JOUR

T1 - A major metabolite of bupropion reverses motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets

AU - Hansard, Matthew J.

AU - Jackson, Michael J.

AU - Smith, Lance A.

AU - Rose, Sarah

AU - Jenner, Peter

PY - 2011/6

Y1 - 2011/6

N2 - The atypical antidepressant, bupropion, causes a partial reversal of motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- treated primates. However, its monoamine uptake blocking actions are believed to be mediated by the major metabolites, racemic (-)-(2R,3R)-2-(3-chlorophenyl-3,5,5-trimethyl-2-morphinol) (R, R-hydroxybupropion) and (+)-(2S,3S)-2-(3-chlorophenyl-3,5,5-trimethyl-2-morphinol) (S,S-hydroxybupropion). Therefore, we have evaluated the ability of enantiomers to improve locomotor activity and motor disability in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets. Bupropion produced a little increase in locomotor activity and a more pronounced improvement in motor disability. The S,S-hydroxybupropion, but not the R,R-hydroxybupropion, enantiomer dose-dependently increased both locomotor activity and reversed motor disability. Combined administration of S,S-hydroxybupropion and R, R-hydroxybupropion at the same dose (analogous to the racemate) again improved motor function and to the same extent as produced by S, S-hydroxybupropion alone. The data suggest that the S,S-enantiomer of hydroxybupropion may possess potential antiparkinsonian activity. Behavioural Pharmacology 22: 269-274 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

AB - The atypical antidepressant, bupropion, causes a partial reversal of motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- treated primates. However, its monoamine uptake blocking actions are believed to be mediated by the major metabolites, racemic (-)-(2R,3R)-2-(3-chlorophenyl-3,5,5-trimethyl-2-morphinol) (R, R-hydroxybupropion) and (+)-(2S,3S)-2-(3-chlorophenyl-3,5,5-trimethyl-2-morphinol) (S,S-hydroxybupropion). Therefore, we have evaluated the ability of enantiomers to improve locomotor activity and motor disability in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets. Bupropion produced a little increase in locomotor activity and a more pronounced improvement in motor disability. The S,S-hydroxybupropion, but not the R,R-hydroxybupropion, enantiomer dose-dependently increased both locomotor activity and reversed motor disability. Combined administration of S,S-hydroxybupropion and R, R-hydroxybupropion at the same dose (analogous to the racemate) again improved motor function and to the same extent as produced by S, S-hydroxybupropion alone. The data suggest that the S,S-enantiomer of hydroxybupropion may possess potential antiparkinsonian activity. Behavioural Pharmacology 22: 269-274 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

U2 - 10.1097/FBP.0b013e328345ca37

DO - 10.1097/FBP.0b013e328345ca37

M3 - Article

VL - 22

SP - 269

EP - 274

JO - Behavioural Pharmacology

JF - Behavioural Pharmacology

IS - 3

ER -