Some neurochemical properties of a new antidepressant, bupropion hydrochloride (Wellbutrin™)
作者:
R. M. Ferris,
H. L. White,
B. R. Cooper,
R. A. Maxwell,
F. L. M. Tang,
O. J. Beaman,
A. Russell,
期刊:
Drug Development Research
(WILEY Available online 1981)
卷期:
Volume 1,
issue 1
页码: 21-35
ISSN:0272-4391
年代: 1981
DOI:10.1002/ddr.430010103
出版商: Wiley Subscription Services, Inc., A Wiley Company
关键词: bupropion;synaptosomes;uptake;release;MAO activity;biogenic amines;tricyclic antidepressants
数据来源: WILEY
摘要:
AbstractBupropion is a novel antidepressant agent. In the present study, an attempt was made to gain some insight into the mechanism of the drug's antidepressant activity. In vitro studies revealed that bupropion was a weak, competitive inhibitor of norepinephrine (NE) uptake into rat hypothalamic synaptosomes and of dopamine (DM) uptake into rat striatal synaptosomes, having IC50 values of 6.5 ± 0.6 × 10−6M and 3.4 ± 0.4 × 10−6M, respectively. At 1 × 10−5M, the drug produced a 20 ± 3% inhibition of serotonin (5‐HT) uptake into rat hypothalamic synaptosomes. The drug was also a weak inhibitor of the ATP‐Mg+2stimulated uptake of NE and DM into synaptic vesicles of whole rat brain, having IC50 values of 3.3 × 10−5M and 6.0 × 10−5M, respectively. Bupropion had no dose‐dependent effect on the spontaneous release of NE, DM, and 5‐HT from these synaptosomal preparations in concentrations as high as 1 × 10−4M. Brain monoamine oxidase (MAO) activity in vitro was not affected by concentrations of the drug ranging from 10−7M to 10−5M. Bupropion was also without effect on brain MAO, 1 hr after i.p. doses in rats as high as 100 mg/kg. The ED50 value for bupropion necessary to inhibit the uptake of3H‐catecholamines by 50% into synaptosomes incubated in the serum from rats treated with the drug was 40 mg/kg i.p., while its ED50 value for antidepressant activity, as judged by the ability of bupropion to reverse the immobile posture of “helpless” rats, was 8 mg/kg i.p. These neurochemical properties of bupropion on uptake of biogenic amines and on MAO activity serve to distinguish it from other antidepressant drugs of t
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