The Experts below are selected from a list of 26898 Experts worldwide ranked by ideXlab platform
Connie Sanchez - One of the best experts on this subject based on the ideXlab platform.
-
EsCitalopram versus Citalopram: the surprising role of the R-enantiomer
Psychopharmacology, 2004Co-Authors: Connie Sanchez, Elin Heldbo Reines, Klaus Peter Bogeso, Bjarke Ebert, Claus BraestrupAbstract:Rationale Citalopram is a racemate consisting of a 1:1 mixture of the R (−)- and S (+)-enantiomers. Non-clinical studies show that the serotonin reuptake inhibitory activity of Citalopram is attributable to the S -enantiomer, esCitalopram. A series of recent non-clinical and clinical studies comparing esCitalopram and Citalopram to placebo found that equivalent doses of these two drugs, i. e. containing the same amount of the S -enantiomer, showed better effect for esCitalopram. These results suggested that the R -Citalopram in Citalopram inhibits the effect of the S -enantiomer. Objective To review the pharmacological and non-clinical literature that describes the inhibition of esCitalopram by R -Citalopram, as well as the implications of this inhibition for the clinical efficacy of esCitalopram compared to Citalopram. Methods The information in this review was gathered from published articles and abstracts. Results In appropriate neurochemical, functional, and behavioural non-clinical experiments, esCitalopram shows greater efficacy and faster onset of action than comparable doses of Citalopram. The lower efficacy of Citalopram in these studies is apparently due to the inhibition of the effect of the S -enantiomer by the R -enantiomer, possibly via an allosteric interaction with the serotonin transporter. Data from randomised clinical trials consistently show better efficacy with esCitalopram than with Citalopram, including higher rates of response and remission, and faster time to symptom relief. Conclusion The R -enantiomer present in Citalopram counteracts the activity of the S -enantiomer, thereby providing a possible basis for the pharmacological and clinical differences observed between Citalopram and esCitalopram.
-
esCitalopram versus Citalopram the surprising role of the r enantiomer
Psychopharmacology, 2004Co-Authors: Connie Sanchez, Elin Heldbo Reines, Klaus Peter Bogeso, Bjarke Ebert, Claus BraestrupAbstract:Rationale Citalopram is a racemate consisting of a 1:1 mixture of the R(−)- and S(+)-enantiomers. Non-clinical studies show that the serotonin reuptake inhibitory activity of Citalopram is attributable to the S-enantiomer, esCitalopram. A series of recent non-clinical and clinical studies comparing esCitalopram and Citalopram to placebo found that equivalent doses of these two drugs, i.e. containing the same amount of the S-enantiomer, showed better effect for esCitalopram. These results suggested that the R-Citalopram in Citalopram inhibits the effect of the S-enantiomer.
-
the r enantiomer of Citalopram counteracts esCitalopram induced increase in extracellular 5 ht in the frontal cortex of freely moving rats
Neuropharmacology, 2003Co-Authors: Arne Mork, M Kreilgaard, Connie SanchezAbstract:Abstract The selective serotonin (5-HT) reuptake inhibitor, Citalopram, is a racemic mixture of an S(+)- and R(−)-enantiomer, esCitalopram and R-Citalopram, respectively. The present study compares the effects of esCitalopram, R-Citalopram and Citalopram on extracellular levels of 5-HT in the frontal cortex of freely moving rats. In addition, co-injection of esCitalopram and R-Citalopram (ratios 1:2 and 1:4) were assessed. In some experiments esCitalopram and R-Citalopram were infused into the frontal cortex by reverse microdialysis. Finally, the extracellular level of esCitalopram in the frontal cortex was studied after administration of esCitalopram alone or in combination with R-Citalopram. EsCitalopram (1.0–3.9 mg/kg, s.c.) produced a greater maximal increase in extracellular 5-HT than Citalopram (2.0–8.0 mg/kg, s.c.). R-Citalopram (15.6 mg/kg s.c.) did not affect the 5-HT levels. When co-injected, R-Citalopram counteracted the esCitalopram-induced increase in extracellular 5-HT levels. Local infusion of the two enantiomers into the frontal cortex produced a similar inhibitory response. R-Citalopram did not influence the extracellular levels of esCitalopram and therefore does not exert its effect via a pharmacokinetic interaction with esCitalopram. In conclusion, the 5-HT-reuptake inhibitory activity of Citalopram resides in esCitalopram, and the R-enantiomer counteracts this effect. This observation would predict an improved clinical profile of esCitalopram compared to Citalopram.
-
esCitalopram the s enantiomer of Citalopram is a selective serotonin reuptake inhibitor with potent effects in animal models predictive of antidepressant and anxiolytic activities
Psychopharmacology, 2003Co-Authors: Connie Sanchez, P B F Bergqvist, Lise T Brennum, S Gupta, Sandra Hogg, Anna Kirstine Larsen, O WiborgAbstract:Objective The pharmacological profile of esCitalopram, the S-(+)-enantiomer of Citalopram, was studied and compared with Citalopram and the R-(−)-enantiomer, R-Citalopram.
-
esCitalopram s enantiomer of Citalopram clinical efficacy and onset of action predicted from a rat model
Pharmacology & Toxicology, 2001Co-Authors: Stuart A Montgomery, Elin Heldbo Reines, Connie Sanchez, Henrik Loft, Mariusz PappAbstract:EsCitalopram is the active S-enantiomer of Citalopram. In a chronic mild stress model of depression in rats, treatments with both esCitalopram and Citalopram were effective; however, a faster time to onset of efficacy compared to vehicle treatment was observed for esCitalopram-treated (5 mg/kg/day) than for Citalopram-treated (10 mg/kg/day) rats at Week 1. To study the predictability of this observation in the clinic, we analysed 4-week data from an 8-week, double-blind, randomised, placebo-controlled, flexible-dose study that compared esCitalopram and Citalopram to placebo in primary care patients with major depressive disorder (baseline Montgomery and Asberg Depression Rating Scale (MADRS) scores > or =22 and < or =40). Since the flexible dosing started after Week 4, analysis of 4-week data ensured that the patients received fixed doses of 10 mg/day esCitalopram (155 patients), 20 mg/day Citalopram (160 patients), or placebo (154 patients). The efficacy analysis showed a significantly superior therapeutic effect for esCitalopram versus placebo from Week 1 onwards (observed cases) with an adjusted mean change in MADRS at Week 4 (last observation carried forward) of 2.7 points (P=0.002). By comparison, 20 mg/day Citalopram did not demonstrate a statistically significant effect compared to placebo. EsCitalopram was well tolerated with an adverse event profile similar to that of Citalopram. The preclinical observation that esCitalopram possesses a faster time to onset of efficacy than Citalopram was also seen in primary care patients with major depressive disorder. Thus, esCitalopram is efficacious in depression and the effect occurs earlier than for Citalopram.
Jules C Hancox - One of the best experts on this subject based on the ideXlab platform.
-
inhibitory actions of the selective serotonin re uptake inhibitor Citalopram on herg and ventricular l type calcium currents
FEBS Letters, 2002Co-Authors: Harry J Witchel, Vijay K Pabbathi, Giovanna Hofmann, Ashok A Paul, Jules C HancoxAbstract:Abstract Using whole-cell patch clamp recording of heterologous HERG-mediated currents in transfected mammalian cells, we observed that the selective serotonin re-uptake inhibitor Citalopram blocks HERG with an IC 50 of 3.97 μM. This is slightly less potent than fluoxetine in our system (IC 50 of 1.50 μM). In isolated guinea pig ventricular cardiomyocytes Citalopram inhibited L-type calcium current ( I Ca,L ). The voltage dependence of I Ca,L inactivation in the presence of 100 μM Citalopram was shifted significantly leftward. As a result, the I Ca,L ‘window’ in Citalopram was found to be (a) smaller and (b) leftward-shifted compared to control. The effects of Citalopram on both calcium current amplitude and the I Ca,L ‘window’ may help to explain Citalopram’s good cardiac safety profile, given its propensity to block HERG at excessive dosages.
C. Monaca Charley - One of the best experts on this subject based on the ideXlab platform.
-
The acute inhibition of rapid eye movement sleep by Citalopram may impair spatial learning and passive avoidance in mice
Journal of Neural Transmission, 2013Co-Authors: A. Bridoux, C. Laloux, P. Derambure, R. Bordet, C. Monaca CharleyAbstract:Rapid eye movement (REM) sleep is known to be essential for memory. Hence, REM sleep deprivation impairs memory processes. The frequently prescribed selective serotonin reuptake inhibitors (SSRIs) are known to cause REM sleep deprivation and to impair cognitive performance in humans and rodents. We suggested that impaired memory processes by Citalopram in C57/BL6 mice could be explained by the acute inhibition of REM sleep. We hypothesized that those acute Citalopram 5 and 10 mg/kg injections induced REM sleep deprivation, altered cognitive performance in passive avoidance, impaired spatial memory compared to controls. Three experiments have been realized: (1) mice received successively physiological saline, injection of Citalopram 5 and 10 mg/kg and were recorded by polysomnographic recording after each injection. (2) Cognitive performance was evaluated in the passive avoidance with two groups of mice. One group received Citalopram before training and one, after training. (3) Spatial learning was evaluated with another group of animals in the Y-maze test. At 5 and 10 mg/kg, Citalopram delayed REM sleep onset and decreased REM sleep amounts (vs. controls). The same doses were administrated in the passive avoidance test and have significantly shortened latency to enter the dark compartment. In the Y-maze, Citalopram-treated mice showed a decreased percentage of time spent in the novel arm in contrast to the two other arms compared with controls. We showed that Citalopram impaired cognitive performance in behavioral tasks. Those impairments could be linked to REM sleep deprivation induced by Citalopram although causal relationship needs to be investigated in further studies.
O Wiborg - One of the best experts on this subject based on the ideXlab platform.
-
esCitalopram the s enantiomer of Citalopram is a selective serotonin reuptake inhibitor with potent effects in animal models predictive of antidepressant and anxiolytic activities
Psychopharmacology, 2003Co-Authors: Connie Sanchez, P B F Bergqvist, Lise T Brennum, S Gupta, Sandra Hogg, Anna Kirstine Larsen, O WiborgAbstract:Objective The pharmacological profile of esCitalopram, the S-(+)-enantiomer of Citalopram, was studied and compared with Citalopram and the R-(−)-enantiomer, R-Citalopram.
Jan Tack - One of the best experts on this subject based on the ideXlab platform.
-
influence of Citalopram a selective serotonin reuptake inhibitor on oesophageal hypersensitivity a double blind placebo controlled study
Alimentary Pharmacology & Therapeutics, 2006Co-Authors: Dorine Broekaert, Benjamin Fischler, Daniel Sifrim, Jozef Janssens, Jan TackAbstract:Summary Background Tricyclic antidepressants, which have multiple pharmacological influences, have a therapeutic effect in non-cardiac chest pain, but selective serotonin reuptake inhibitors have a single pharmacological effect. Aim To evaluate the acute effect of Citalopram on oesophageal hypersensitivity. Methods On two separate occasions, 10 healthy subjects (seven men, mean age 25 years) with established oesophageal hypersensitivity, underwent oesophageal manometry with evaluation of mechanical and chemical sensitivity. Subjects received placebo or Citalopram 20 mg i.v. in a randomized, crossover, double-blind fashion. Results Citalopram did not alter oesophageal motility. Citalopram significantly increased the threshold inducing first perception (4.6 ± 0.3 vs. 6.7 ± 0.4 mL, P < 0.005) and discomfort (8.6 ± 0.4 vs. 9.9 ± 0.6 mL, P < 0.01) during balloon distention. It also significantly prolonged the acid perfusion time to induce perception of heartburn (6.0 ± 0.9 vs. 10.7 ± 0.6 min, P < 0.005) and discomfort (12.2 ± 0.8 vs. 16.7 ± 0.7 mL, P < 0.001). Seven subjects experienced a retrosternal sensation during edrophonium provocation with placebo, and this was reduced to two of 10 after Citalopram (P = 0.02). Conclusions Acute administration of Citalopram significantly lowers chemical and mechanical oesophageal sensitivity in oesophageal hypersensitivity, without altering the motility.