Dibenzoazepine analogues: the electrophysiological properties of JL3, a potential atypical antidepressant.
JL3, 10-(4-methylpiperazin-1-yl)pyrido[4,3-b][1,4]benzothiazepine, has potent antidepressant-like activity in Porsolt's test in mice. Therefore, its influence on the electrical activity of central monoaminergic neurons was investigated in rats anaesthetized with chloral hydrate. JL3 induced a marked decrease of the firing rate of dorsal raphe serotonergic neurons (ID50 = 3.87 +/- 0.57 mg kg-1) and of locus coeruleus noradrenergic neurons (ID50 = 2.63 +/- 0.35 mg kg-1). The drug did not modify the electrical activity of A10 dopaminergic neurons. JL3 does not block amine uptake but it has affinity for 5-HT1A and 5-HT2 receptors. It is speculated that serotonergic mechanisms could play a role in the electrophysiological effects of JL3.
Liégeois
J F
JF
Laboratory of Medicinal Chemistry, University of Liège, Belgium.
Scuvée-Moreau
J
J
Giesbers
I
I
Damas
J
J
Bruhwyler
J
J
Géczy
J
J
Delarge
J
J
Dresse
A
A
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006801:Humans; D008125:Locus Coeruleus / Q000187:drug effects; D011903:Raphe Nuclei / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013841:Thiazepines / Q000494:pharmacology*
D000928:Antidepressive Agents; D013841:Thiazepines; C103197:10-(4-methylpiperazin-1-yl)pyrido(4,3-b)(1,4)benzothiazepine