Effects of JL 3, a putative antidepressant, on rat noradrenergic and serotonergic systems

J Liégeois; V Seutin; J Scuvée-Moreau; A Dresse; J Bruhwyler; J Géczy; J Delarge; J Damas

doi:10.1016/s0014-2999(99)00777-3

Effects of JL 3, a putative antidepressant, on rat noradrenergic and serotonergic systems

Eur J Pharmacol. 1999 Dec 15;386(2-3):211-6. doi: 10.1016/s0014-2999(99)00777-3.

Authors

J Liégeois¹, V Seutin, J Scuvée-Moreau, A Dresse, J Bruhwyler, J Géczy, J Delarge, J Damas

Affiliation

¹ Laboratory of Medicinal Chemistry, University of Liège, 1 avenue de l'Hôpital (B36), B-4000, Liège, Belgium. jf.liegeois@ulg.ac.be

PMID: 10618472
DOI: 10.1016/s0014-2999(99)00777-3

Abstract

Using in vitro electrophysiological procedures, we confirm the inhibitory effect of 10-(4-methylpiperazin-1-yl)pyrido[4,3-b][1, 4]benzothiazepine (JL 3), on dorsal raphe serotonergic (IC(50)=14 microM) and noradrenergic neurons (IC(50)=4.5 microM). The effect on dorsal raphe neurons was reduced by N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl- cyclohexanecarboxamide (WAY-100635), suggesting the importance of 5-HT(1A) receptor stimulation. Yohimbine, and ritanserin, to a lesser extent, blocked the inhibitory effect of JL 3 on locus coeruleus neurons indicating that alpha(2)-adrenoceptors and 5-HT(2A) receptors may be implicated in the effects. Because of its negligible alpha(2)-adrenoceptor affinity, the effect of JL 3 on locus coeruleus neurons, would have to be indirect. JL 3 may interfere with the norepinephrine transporter site (IC(50)=0.34 microM). JL 3 tended to reinforce the hypertensive effect of norepinephrine, while it strongly inhibited the hypertensive effect of tyramine, further indicating an interaction at the norepinephrine transporter site level.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenergic Uptake Inhibitors / pharmacology
Animals
Antidepressive Agents / pharmacology*
Drug Interactions
In Vitro Techniques
Locus Coeruleus / drug effects
Locus Coeruleus / metabolism
Male
Neurons / drug effects*
Neurons / metabolism
Norepinephrine / pharmacology
Raphe Nuclei / drug effects
Raphe Nuclei / metabolism
Rats
Rats, Wistar
Receptors, Adrenergic / metabolism*
Receptors, Serotonin / metabolism*
Thiazepines / pharmacology*
Tyramine / pharmacology

Substances

Adrenergic Uptake Inhibitors
Antidepressive Agents
Receptors, Adrenergic
Receptors, Serotonin
Thiazepines
10-(4-methylpiperazin-1-yl)pyrido(4,3-b)(1,4)benzothiazepine
Norepinephrine
Tyramine