PHARMACOLOGICAL PROPERTIES OF 403U76, A NEW CHEMICAL CLASS OF 5-HYDROXYTRYPTAMINE-REUPTAKE AND NORADRENALINE-REUPTAKE INHIBITOR

被引：38

作者：

FERRIS, RM ^{[1
]}

BRIEADDY, L ^{[1
]}

MEHTA, N ^{[1
]}

HOLLINGSWORTH, E ^{[1
]}

RIGDON, G ^{[1
]}

WANG, C ^{[1
]}

SOROKO, F ^{[1
]}

WASTILA, W ^{[1
]}

COOPER, B ^{[1
]}

机构：

[1] WELLCOME RES LABS,ORGAN CHEM,RES TRIANGLE PK,NC 27709

来源：

JOURNAL OF PHARMACY AND PHARMACOLOGY | 1995年 / 47卷 / 09期

关键词：

D O I：

10.1111/j.2042-7158.1995.tb06740.x

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

403U76 (5-chloro-[[2-[(dimethylamino)methyl]phenyl]thio]benzene-methanol hydrochloride) is a potent, competitive, inhibitor of 5-hydroxytryptamine (5-HT) and noradenaline reuptake into rat brain synaptosomes. Inhibition of 5-HT uptake in-vivo by 403U76 was demonstrated by potentiation of the behavioural effects of 5-hydroxytryptophan in rats and mice and blockade of p-induced depletion of 5-HT in rats. The firing of 5-HT-ergic dorsal raphe neurons in rats was decreased after intravenous administration of low doses of 403U76 as would be predicted for a 5-HT uptake inhibitor. 403U76 antagonized tetrabenazine-induced sedation, an effect associated with inhibitors of noradrenaline uptake, but not with inhibitors of 5-HT uptake. Thus 403U76 affects noradrenergic as well as 5-HT-ergic neurotransmission in-vivo. Potential anxlolytic activity was indicated by reductions in isolation-induced vocalizations in neonates after 403U76 treatment. Low intravenous doses of 403U76 were well tolerated and had no sustained cardiovascular effects. There were no deleterious behavioural side-effects at active doses. Effects observed on isolated tissues or transmitter receptors occurred only at very high concentrations and were pharmacologically unimportant. Thus 403U76 can be considered a potential antidepressant/anxiolytic agent that is a potent, selective inhibitor of 5-HT and noradrenaline reuptake.

引用

页码：775 / 781

页数：7

共 29 条

[1] LYSERGIC-ACID DIETHYLAMIDE AND SEROTONIN - DIRECT ACTION ON SEROTONIN-CONTAINING NEURONS IN RAT-BRAIN [J].