RT Journal Article
SR Electronic
T1 Differences in modulation of noradrenergic and serotonergic transmission by the alpha-2 adrenoceptor antagonists, mirtazapine, mianserin and idazoxan.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 852
OP 860
VO 277
IS 2
A1 T H de Boer
A1 F Nefkens
A1 A van Helvoirt
A1 A M van Delft
YR 1996
UL http://jpet.aspetjournals.org/content/277/2/852.abstract
AB The effects of three compounds with alpha-2 adrenoceptor antagonistic properties, mirtazapine (Org 3770; Remeron), mianserin and idazoxan, were measured on hippocampal noradrenergic and serotonergic transmission in freely moving rats by using microdialysis. Dihydroxyphenylacetic acid (DOPAC) was measured as a correlate of noradrenergic presynaptic activity. Infusing 1 microM tetrodotoxin decreased extracellular serotonin (5-HT) and DOPAC by 65 and 40%, respectively. 5-Hydroxytryptophan (25 mg/kg s.c.) increased extracellular 5-HT by 500%, whereas 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (0.5 mg/kg s.c.) decreased 5-HT release by 60%. Prazosin decreased 5-HT release to 60% of base-line in agreement with an alpha-1-mediated control of 5-HT transmission, whereas it increased DOPAC release with 80%. Both mirtazapine (2 and 5 mg/kg s.c.) and idazoxan (1 mg/kg s.c.) caused a rapid increase in DOPAC by up to 80%. Mianserin slowly increased DOPAC, reaching a maximal increase of 30 and 60% at 2 and 5 mg/kg s.c., respectively. Only mirtazapine caused a concurrent increase in 5-HT, reaching up to 80% above base-line within 60 min, whereas mianserin and idazoxan failed to change 5-HT levels significantly. Mirtazapine (5 mg/kg s.c.) only slightly affected DOPAC and homovanillic acid levels in the striatum, hardly affected 5-HT release, but clearly increased 5-hydroxyindole acetic acid. Thus, the antidepressants mirtazapine and mianserin markedly differ in their effects on noradrenergic and serotonergic transmission in vivo as measured with microdialysis in freely moving rats. These differences are explained by their different modulatory effects on noradrenergic transmission.