Citalopram — Pharmacological profile of a specific serotonin uptake inhibitor with antidepressant activity

Serotonin Reuptake Inhibition by Citalopram in Rat Strains Differing for Their Emotionality

“…Although such an in vitro potency (17-25 nM) was almost similar to that reported in cortical synaptosomes (K i ϭ 11.2 nM) (Wong et al 1991), it was one range lower than that reported using whole brain (K i ϭ 1.5 nM) (Hyttel 1982) or hypothalamus (K i ϭ 2.6 nM) (Thomas et al 1987) synaptosomes, a difference that is likely to be accounted for by strain, region and/or [ 3 H]5-HT reuptake preparation differences. Of note was the observation that 1 M citalopram did not fully block [ 3 H]5-HT reuptake in hippocampus or striatum.…”

“…Of note was the observation that 1 M citalopram did not fully block [ 3 H]5-HT reuptake in hippocampus or striatum. Actually, the observation that as much as 12-16% (hippocampus) or 23-25% (striatum) of [ 3 H]5-HT reuptake was resistant to citalopram could be linked to previous ones, obtained by means of chronoamperometry and microdialysis, and which indicated that a significant amount of hippocampal and striatal 5-HT may respectively undergo reuptake by noradrenergic (Daws et al 1998) and dopaminergic (De Deurwaerdère et al 1996) transporters, targets for which citalopram shows weak affinity (K i ϭ 5.75 and 36.61 M, respectively) (Hyttel 1982). Whatever the nature of that citalopram-resistant portion, our results show that the three rat strains differed neither with respect to the SSRI property of citalopram (as indicated by the respective K i s) nor with respect to that citalopram-resistant portion (as indicated by the respective lower plateau levels).…”

“…With regard to the aforementioned findings, this study examined whether rat strains differing with respect to some dimensions of their emotionality (specifically, anxiety and locomotor reactivity) displayed trait variability in: (i) the effectiveness of the 5-HT reuptake system; and/or (ii) the ability of citalopram, the most selective and amongst the most potent 5-HT reuptake inhibitor(s) (Hyttel 1982(Hyttel , 1994 to block that system. To this end, we chose the SHRs, LEW, and WKY inbred strains since SHRs (which derive from WKY rats) (Okamoto and Aoki 1963) display low anxiety but high activity, whereas LEW rats are anxious and normoactive, and WKY rats are anxious and hypoactive (Gentsch et al 1987;Paré 1989;Ramos et al 1997).…”

5-HT1A/1B Receptor-Mediated Effects of the Selective Serotonin Reuptake Inhibitor, Citalopram, on Sleep: Studies in 5-HT1A and 5-HT1B Knockout Mice

“…We analyzed the effects of citalopram, the most selective SSRI currently available (Hyttel, 1982;Milne and Goa, 1991), on sleep-wakefulness cycles in 5-HT 1A and 5-HT 1B knockout mice and their wild-type counterparts. In addition, we investigated whether pharmacological blockade of either 5-HT 1A or 5-HT 1B receptors with selective antagonists could prevent the effects of citalopram on sleep in the mouse.…”

5-HT1B Receptors: A Novel Target for Lithium Possible Involvement in Mood Disorders

“…A major one is interaction with its inactivating process, particularly the synaptosomal reuptake system, which is the target for classical antidepressant drugs as specific serotonin reuptake inhibitors (SSRIs) (Hyttel 1982;Owen et al 1997), and other ways consist in altering the activity of presynaptic 5-HT autoreceptors; that is, 5-HT 1A and 5-HT 1B receptor subtypes. 5-HT 1A autoreceptors are localized on the soma and dendrites of the 5-HT neurons and control their firing; whereas, 5-HT 1B autoreceptors are localized on neuron terminals, where they are especially dedicated to the auto control of the release of 5-HT (Hoyer et al 1994).…”