[The role of type 2 serotonin receptors, 5-HT2A and 5-HT2C, in depressive disorders: effect of medifoxamine].
The serotonin (5-HT) is implicated in many centrally-regulated functions and has shown to be involved in affective disorders, such as depression and anxiety disorders. Recent progress in pharmacology and molecular neurobiology have confirmed the concept of the heterogeneity of 5-HT receptors and permitted reformulation of new hypothesis concerning antidepressant mechanisms of action, in particular those concerning serotoninergic receptors. Up to date, among the 5-HT defined sites, only 13 have been cloned, and several subfamilies have been described. Particularly, the 5-HT1 family containing receptors: 5-HT1A, 5-HT1B/1D, 5-HT1E and 5-HT1F. The 5-HT2 family includes receptors that stimulate phospholipase C: 5-HT2A (previously termed 5-HT2), 5-HT2B and 5-HT2C (previously termed 5-HT1C). Concerning 5-HT2 family, it is possible that some 5-HT binding drugs properties initially attributed to 5-HT2A receptors, might well be mediated by 5-HT2C receptors. Recently, medifoxamine (Cledial) activities on 5-HT systems have been shown. In particular, these activities are related on 5-HT2C and/or 5-HT2A binding sites. Results indicate that, in vitro, medifoxamine affinities (Ki) are near to 1 microM, for both 5-HT2C and 5-HT2A sites (ratio = 1.42). On the other hand, m-CPP, an 5-HT2C agonist, considered as a reference compound, has the same affinities that medifoxamine, but a higher one for 5-HT2A (ratio = 3.42). In animals models considered as predictive for psychotropic activity in human, we investigate in rat the impact of medifoxamine on 5-HT2C receptors, using Learned-Helplessness model (LH) and the social interaction test.(ABSTRACT TRUNCATED AT 250 WORDS)
Martin
P
P
AMC Research Group, Hôpital Robert Debré, Paris.
Lemonnier
F
F
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005021:Ethylamines / Q000494:pharmacology*; D006380:Helplessness, Learned; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D012919:Social Behavior
D000928:Antidepressive Agents; D005021:Ethylamines; D011985:Receptors, Serotonin; C034065:medifoxamine; D007099:Imipramine
Intérêt des récepteurs sérotoninergiques de type 2, 5-HT2A et 5-HT2C, dans les troubles dépressifs: action de la médifoxamine.