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Published on: September 23, 2015
The alpha 2-adrenoceptor antagonist Org 3770 enhances serotonin transmission in vivo
T De Boer1, F Nefkens, A Van Helvoirt
1Department of Neuropharmacology, N.V. Organon, Oss, Netherlands.
Abstract:
The antidepressant properties of Org 3770 (1,2,3,4,10,14b-hexahydro-2-methylpyrazino[2,1-a]pyrido[2,3- c][2]benzazepine) may be mediated via blockade of auto and hetero alpha 2-adrenoceptors. On-line microdialysis studies in freely moving rats showed Org 3770 (2 mg/kg s.c.) to increase hippocampal 5-HT (5-hydroxytryptamine) and dihydroxyphenyl acetic acid (DOPAC)--a measure of noradrenergic activity--by approximately 80%. The increase in DOPAC is probably caused by blockade of alpha 2-autoreceptors on noradrenergic terminals. Indirect alpha 1-adrenoceptor-mediated enhancement of 5-HT cell firing and direct blockade of inhibitory alpha 2-heteroreceptors located on 5-HT terminals are held responsible for the increase in extracellular 5-HT.
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