citalopram escitalopram Lexapro
Relationship between clinical effects, serum drug concentration, and concurrent drug interactions in depressed patients treated with citalopram, fluoxetine, clomipramine, paroxetine or venlafaxine.

Charlier C, Pinto E, Ansseau M, Plomteux G.

University of Liege, Toxicology Laboratory, CHU Sart Tilman, B-4000 Liege, Belgium.

The relationship between clinical effects and plasma concentrations of citalopram, fluoxetine, clomipramine, paroxetine and venlafaxine was studied in 119 cases of major depression. Clinical effects were evaluated using the Clinical Global Impression (CGI) improvement scale. Antidepressants were quantified by a separative chromatographic methodology. Plasma concentrations in responder patients were compared with the plasma concentrations proposed in literature as effective values. We found that the usual therapeutic window is convenient for citalopram and clomipramine, but could be reduced for fluoxetine and increased for venlafaxine and paroxetine. Concurrent drug interactions were also evaluated and clomipramine or citalopram plasma levels were found to be influenced by the presence of associated drugs. A larger study is needed, taking into account not only plasma concentrations and clinical effects, but also some pharmacokinetic data, especially the metabolic activity characterising the patient, and the presence or not of associated drugs. Copyright 2000 John Wiley & Sons, Ltd.

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citalopram escitalopram Lexapro
Partial 5-HT1A receptor agonist properties of (-)pindolol in combination with citalopram on serotonergic dorsal raphe cell firing in vivo.

Arborelius L, Linner L, Wallsten C, Ahlenius S, Svensson TH.

Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden. Lotta.Arborelius fyfa.ki.se

RATIONALE: Pindolol has been reported to shorten the onset of antidepressant action of selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) as well as to increase their efficacy. It has been postulated that pindolol enhances the antidepressant effect of SSRIs by blocking somatodendritic 5-HT1A autoreceptors, thus antagonizing the SSRI-induced feedback inhibition of midbrain 5-HT cell firing. A recent study, however, found that pindolol suppresses the firing rate of central 5-HT cells, suggesting that the compound possesses agonistic activity at 5-HT1A autoreceptors. OBJECTIVES: The purpose of the present study was to investigate if acute administration of (-)pindolol antagonizes the decrease in firing rate of dorsal raphe 5-HT cells produced by acute treatment with the SSRI citalopram. METHODS: Extracellular recordings of single 5-HT neurons in the dorsal raphe nucleus in anaesthetized rats. RESULTS: Administration of 0.25 or 3.0 mg/kg (IV) (-)pindolol alone decreased the firing rate of a majority of the 5-HT cells studied, an effect that was reversed by the 5-HT1A receptor antagonist WAY 100635 (0.1 mg/kg, IV). Neither 0.25 nor 3.0 mg/kg (-)pindolol reversed the citalopram (0.1-0.2 mg/kg. IV)-induced suppression of 5-HT cell activity, but produced a further decrease in firing rate. In contrast, WAY100635 (0.1 mg/kg) completely reversed this effect of citalopram. Yet, pretreatment with 3.0, but not 0.25 mg/kg (-)pindolol significantly attenuated the acute inhibitory effect of citalopram on serotonergic cell firing. CONCLUSIONS: The present findings support the previous notion that (-)pindolol possesses prominent agonistic activity at somatodendritic 5-HT1A autoreceptors, but also indicate that it may possess a weak antagonistic action at these receptors.

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citalopram escitalopram Lexapro
Endogenous serotonin enhances the release of dopamine in the striatum only when nigro-striatal dopaminergic transmission is activated.

Lucas G, De Deurwaerdere P, Porras G, Spampinato U.

Laboratoire de Neuropsychobiologie des Desadaptations, UMR-CNRS 5541, Universite Victor Segalen Bordeaux 2, Boite Postale 31, 146, rue Leo Saignat, 33076 Bordeaux Cedex, France.

In this study, we use in vivo microdialysis to investigate the influence of endogenous serotonin (5-HT) on striatal dopamine (DA) and 5-hydroxyidoleacetic acid (5-HIAA) efflux in both basal and activated conditions. The selective serotonin reuptake inhibitors citalopram and fluoxetine were used to mobilize endogenous 5-HT.In halothane-anaesthetized rats, citalopram (5 mg/kg, i.p.), administered either alone or in combination with the 5-HT(1A) receptor antagonist WAY 100635 (0.1 mg/kg, s.c.), while reducing striatal 5-HIAA outflow (-25 and -15%, respectively), had no effect on basal DA output. When locally applied into the striatum, citalopram had no effect at 1 microM concentration, but enhanced DA release after its perfusion at 25 and 100 mircroM concentrations (+27% and +67%, respectively). However, the injection of the neurotoxin 5,7-dihydroxytryptamine into the dorsal raphe nucleus, which markedly depleted 5-HT in the striatum, failed to modify the effect of 25 microM citalopram.In freely-moving rats, the intrastriatal infusion of citalopram or fluoxetine (1 microM each), had no effect on its own, but significantly enhanced the increase in DA outflow induced by the subcutaneous administration of 0.01 mg/kg haloperidol (+31% and +30% for citalopram and fluoxetine, respectively).These findings indicate that, in the striatum, endogenous 5-HT has no influence on DA release under basal conditions, but positively modulates DA outflow when nigro-striatal DA transmission is activated.

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citalopram escitalopram Lexapro
Inhibition of 5-hydroxytryptamine reuptake by the antidepressant citalopram in the locus coeruleus modulates the rat brain noradrenergic transmission in vivo.

Mateo Y, Ruiz-Ortega JA, Pineda J, Ugedo L, Meana JJ.

Department of Pharmacology, University of the Basque Country, E-48940 Leioa, Bizkaia, Spain.

The in vivo effect of the serotonin (5-HT) reuptake inhibitor antidepressant citalopram, administered in the locus coeruleus (LC), on noradrenergic transmission was evaluated in the rat brain. In dual-probe microdialysis assays, citalopram (0.1-100 microM), in a concentration-dependent manner, increased extracellular noradrenaline (NA) in the LC and simultaneously decreased extracellular NA in the cingulate cortex (Cg). These effects of citalopram were abolished by pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (400 mg/kg, i.p.). When the alpha(2)-adrenoceptor antagonist RS79948 (1 microM) was perfused in the LC, local citalopram increased NA dialysate in the LC but no longer modified NA dialysate in the Cg. In electrophysiological experiments, the administration of citalopram (100 microM) in the LC by reversal dialysis, decreased the firing rate of LC neurones. The results demonstrate in vivo that local administration of citalopram in the LC leads to a decreased release of NA in the Cg. This modulation seems to be the result of an increase in NA concentration in the LC and the subsequent inhibition of LC neurones via alpha(2)-adrenoceptors. The effects of citalopram are dependent on the presence of endogenous 5-HT in the LC.

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citalopram escitalopram Lexapro
The use of citalopram in resistant cataplexy.

Thirumalai SS, Shubin RA.

Huntington Hospital Sleep Disorders Center, 100 West California Boulevard, CA 91107, Pasadena, USA

Background: Cataplexy is a disabling component of the narcolepsy tetrad that is sometimes resistant to standard treatment.Case reports: Three of our patients with narcolepsy, including one who had post-traumatic narcolepsy, suffered from intractable cataplexy with failure of treatment with established drugs due to unacceptable side-effects.Results: We explored the use of citalopram (Celexa), the newest and most specific of the serotonin reuptake inhibitors, and were successful in treating cataplexy without significant side-effects. Stimulant drugs remained necessary for controlling symptoms of excessive drowsiness.Conclusions: Citalopram was effective in relieving the symptoms of resistant cataplexy in out patients.

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citalopram escitalopram Lexapro
Which neuroreceptors mediate the subjective effects of MDMA in humans? A summary of mechanistic studies.

Liechti ME, Vollenweider FX.

Clinical Research Unit, University Hospital of Psychiatry, Zurich, Switzerland.

In preclinical studies, 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') has been shown to release serotonin (5-HT), dopamine and norepinephrine. However, the role of these neurotransmitters and their corresponding receptor sites in mediating the subjective effects of MDMA has not yet been studied in humans. Therefore, we investigated the effects of three different neuroreceptor pretreatments on the subjective, cardiovascular and adverse effects of MDMA (1.5 mg/kg orally) in 44 healthy human volunteers. Pretreatments were: the selective serotonin reuptake inhibitor citalopram (40 mg intravenously) in 16 subjects, the 5-HT(2) antagonist ketanserin (50 mg orally) in 14 subjects, and the D(2) antagonist haloperidol (1.4 mg intravenously) in 14 subjects. Each of these studies used a double-blind placebo-controlled within-subject design and all subjects were examined under placebo, pretreatment, MDMA and pretreatment plus MDMA conditions. Citalopram markedly reduced most of the subjective effects of MDMA, including positive mood, increased extraversion and self-confidence. Cardiovascular and adverse effects of MDMA were also attenuated by citalopram. Haloperidol selectively reduced MDMA-induced positive mood but had no effect on other subjective effects of MDMA or the cardiovascular or adverse responses to MDMA. Ketanserin selectively reduced MDMA-induced perceptual changes and emotional excitation. These results indicate that the overall psychological effects of MDMA largely depend on carrier-mediated 5-HT release, while the more stimulant-like euphoric mood effects of MDMA appear to relate, at least in part, to dopamine D(2) receptor stimulation. The mild hallucinogen-like perceptual effects of MDMA appear to be due to serotonergic 5-HT(2) receptor stimulation. Copyright 2001 John Wiley & Sons, Ltd.

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citalopram escitalopram Lexapro
Effects of repeated fluoxetine and citalopram administration on cytokine release in C57BL/6 mice.

Kubera M, Simbirtsev A, Mathison R, Maes M.

Department of Endocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland.

This study examines the effects of repeated administration of the selective serotonin reuptake inhibitors (SSRIs), fluoxetine and citalopram (10 mg/kg, i.p.), on immunoreactivity in C57BL/6 mice. Immune functions were evaluated by the ability of splenocytes to reduce a tetrazolium salt to formazan (MTT test), to proliferate, and to produce cytokines, including interleukin (IL)-1, IL-2, IL-4, IL-6, IL-10 and interferon gamma (IFN gamma). Citalopram administered for 1, 2 and 4 weeks stimulates the proliferative activity of splenocytes and suppresses their ability to secrete the anti-inflammatory cytokine IL-4. Fluoxetine administration for 1 and 2 weeks, but not 4 weeks, stimulates the proliferative activity of splenocytes, whereas a 4-week administration of fluoxetine suppresses the secretion of IL-4. Four weeks of prolonged administration of citalopram and fluoxetine induces a significant increase in the production of IL-6 and IL-10, a cytokine with immunosuppressive and anti-inflammatory activities. The results show that, in C57BL/6 mice, the immunomodulatory effects of SSRIs depend on the SSRI used and the duration of administration.

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