The alpha 2-adrenoceptor antagonist Org 3770 enhances serotonin transmission in vivo.
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.
De Boer
T
T
Department of Neuropharmacology, N.V. Organon, Oss, Netherlands.
Nefkens
F
F
Van Helvoirt
A
A
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007279:Injections, Subcutaneous; D008297:Male; D008803:Mianserin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D017551:Microdialysis; D000078785:Mirtazapine; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D000929:Antidepressive Agents, Tricyclic; D015102:3,4-Dihydroxyphenylacetic Acid; D008803:Mianserin; D012701:Serotonin; D000078785:Mirtazapine