citalopram escitalopram Lexapro
Citalopram as an inhibitor of voluntary ethanol intake in the male rat.

Hedlund L, Wahlstrom G.

Department of Pharmacology, Umea University, Sweden.

Psychological dependence was induced in rats by a 1-year intermittent exposure to intoxicating doses of ethanol, and recorded by the rat's ability to later take the same dose of ethanol independent of the offered concentration. Citalopram (10 or 40 mg/kg/day) was given for 3 weeks with ethanol available only the first and the last day; 10 mg/kg had no effect. On the first treatment day 40 mg/kg decreased ethanol intake. On the last treatment day 40 mg/kg had no effect. The following week the ethanol intake was higher than before the treatment in the 40 mg/kg group. During the four posttreatment weeks the ethanol intake of the 40 mg/kg group dropped significantly. Citalopram was retested 18 weeks after the first treatment during 1 week, with continuous access to ethanol; 10 mg/kg had no effect and 40 mg/kg decreased ethanol intake at day 1, reaching a minimum in day 3. A tolerance to this effect was seen at the end of the week. Thus, in this model an acute dose of citalopram can decrease ethanol intake, but tolerance to this effect develops when citalopram is given both with and without access to ethanol.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9818981&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Analysis of the enantiomers of citalopram and its demethylated metabolites using chiral liquid chromatography.

Kosel M, Eap CB, Amey M, Baumann P.

Unite de Biochimie et Psychopharmacologie Clinique, Departement Universitaire de Psychiatrie Adulte, Prilly-Lausanne, Switzerland.

A procedure using a chirobiotic V column is presented which allows separation of the enantiomers of citalopram and its two N-demethylated metabolites, and of the internal standard, alprenolol, in human plasma. Citalopram, demethylcitalopram and didemethylcitalopram, as well as the internal standard, were recovered from plasma by liquid-liquid extraction. The limits of quantification were found to be 5 ng/ml for each enantiomer of citalopram and demethylcitalopram, and 7.5 ng/ml for each enantiomer of didemethylcitalopram. Inter- and intra-day coefficients of variation varied from 2.4% to 8.6% for S- and R-citalopram, from 2.9% to 7.4% for S- and R-demethylcitalopram, and from 5.6% to 12.4% for S- and R- didemethylcitalopram. No interference was observed from endogenous compounds following the extraction of plasma samples from 10 different patients treated with citalopram. This method allows accurate quantification for each enantiomer and is, therefore, well suited for pharmacokinetic and drug interaction investigations. The presented method replaces a previously described highly sensitive and selective high-performance liquid chromatography procedure using an acetylated 3-cyclobond column which, because of manufactural problems, is no longer usable for the separation of the enantiomers of citalopram and its demethylated metabolites.

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citalopram escitalopram Lexapro
Acute and chronic citalopram treatment differently modulates rat exploratory behavior in the exploration box test: no evidence for increased anxiety or changes in the [3H]raclopride binding.

Matto V, Allikmets L.

Department of Pharmacology, University of Tartu, Estonia. vallo ut.ee

The effect of acute and chronic desipramine (10 mg/kg) and citalopram (10 mg/kg) treatment on rat exploratory behavior in the recently developed exploration box test was studied on 5 consecutive days. Acute desipramine but not citalopram treatment decreased the time spent exploring, the number of line crossings, rears, investigative approaches, entries into the large arena, and sum of exploratory events. After 3 weeks of pretreatment, both desipramine and citalopram attenuated rat exploratory behavior, whereas the number of entries into the large arena was unchanged. In the open field test, acute desipramine or citalopram treatment (5, 10, 15 mg/kg) attenuated rat exploratory behavior in a dose-dependent manner. In the subsequent rota-rod test, neither desipramine nor citalopram treatment (0-20 mg/kg) impaired motor performance capacity. In an additional experiment, [3H]raclopride binding was unchanged after single as well as 3 weeks of desipramine or citalopram treatment in the rat brain neostriatum. Our experiments demonstrate that acute citalopram treatment in the open field test and chronic citalopram treatment in the exploration box test attenuate rat exploratory behavior, but these effects may not be implicated with enhanced anxiety or changed dopamine D2 receptor characteristics.

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citalopram escitalopram Lexapro
Citalopram elicits a discriminative stimulus in rats at a dose selectively increasing extracellular levels of serotonin vs. dopamine and noradrenaline.

Millan MJ, Gobert A, Girardon S, Dekeyne A.

Department of Psychopharmacology, Institut de Recherches Servier, Croissy-sur-Seine, Paris, France.

Citalopram (2.5 mg/kg, i.p.) increased (+145-+180%) extracellular levels of serotonin (5-hydroxytryptamine, 5-HT) in the frontal cortex, nucleus accumbens and striatum of freely-moving rats, whereas dopamine and noradrenaline were unaffected. At this dose, employing a two-lever, food-reinforced, drug discrimination procedure, citalopram generated reliable recognition and fully (> 80%) generalized to itself with an Effective Dose50 (ED50) of 0.1 mg/kg, s.c. Two further selective 5-HT reuptake inhibitors, sertraline and paroxetine, fully generalized with ED50s of 0.01 and 0.04 mg/kg, s.c., respectively. In contrast, the anxiolytic, diazepam (0.63), and the antipsychotic, clozapine (2.5), did not (< or = 20%) generalize. In conclusion, the selective 5-HT reuptake inhibitor, citalopram, elicits a pharmacologically-specific discriminative stimulus in rats at a dose selectively elevating extracellular concentrations of 5-HT.

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citalopram escitalopram Lexapro
Repeated citalopram treatment but not stress exposure attenuates hypothalamic-pituitary-adrenocortical axis response to acute citalopram injection.

Moncek F, Duncko R, Jezova D.

Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, 83306 Bratislava, Slovakia.

Many experimental, clinical and epidemiological studies have shown a direct connection between exposure to stress or adverse life events and disease, but little is known about the effect of stress on the action of drugs. The aim of this study was to test the hypothesis that previous exposure to stress changes the action of the antidepressant drug citalopram (10 mg/kg, i.p.) on hypothalamic-pituitary-adrenocortical (HPA) axis function, gene expression of selected neuropeptides and serotonin reuptake. Three different stress models were used, which included immobilization, restraint and unpredictable stress stimuli. Samples of plasma for hormone measurement were taken from conscious cannulated animals. Changes in corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC) gene expression in the paraventricular nucleus of the hypothalamus and the anterior pituitary, respectively, and the ability of citalopram to inhibit serotonin reuptake were investigated. The exposure to three different stress models did not influence citalopram action on individual parameters of HPA axis and on serotonin reuptake. On the other hand, repeated administration of the drug led to significant attenuation of ACTH and CRH mRNA responses. The present results allow to suggest that the stressors used did not influence serotonergic neurotransmission to the extent that would modify HPA axis response to citalopram challenge. Activation of HPA axis by acute citalopram treatment was found to be accompanied by increased CRH gene expression in the hypothalamus. Repeated administration of the drug led to the development of tolerance to activation of central and peripheral components of HPA axis, but not to serotonin reuptake inhibition.

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citalopram escitalopram Lexapro
A Markov process analysis comparing the cost effectiveness of maintenance therapy with citalopram versus standard therapy in major depression.

Nuijten MJ, Hardens M, Souetre E.

Benefit Research Group, Leiden, The Netherlands.

The objective of this study was to demonstrate the cost effectiveness of long term maintenance treatment with citalopram versus standard therapy (defined as short term antidepressant treatment) in patients with major depression in Germany. We chose doxepin, amitriptyline and trimipramine as standard therapy because these drugs are the leading antidepressants in that country. A Markov process analysis was used to model health status and economic outcomes as they accrued over a 1-year follow-up period. The main outcome measures were time without depression, direct costs and indirect costs (work days lost). All costs were in 1993 Deutsche marks. The clinical data were obtained from the published literature and US clinical practice guidelines; the associated unit costs of the medical resources used were derived from official German tariff lists. The results show that, compared with standard therapy, long-term maintenance treatment with citalopram is associated with a mean increase in time without depression of 7.9% (8.2 vs 7.6 months). The total costs of maintenance treatment with citalopram were substantially lower than with standard therapy (DM7985 vs DM11,948 per patient per year. In addition, both the direct and indirect costs of maintenance treatment with citalopram (DM3764 vs DM4221 per patient, respectively) were lower than with standard therapy (DM4577 vs DM7371 per patient, respectively). In conclusion, the study demonstrates that one year's maintenance treatment with citalopram is both more effective and less costly than standard therapy in the treatment of patients with major depression.

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citalopram escitalopram Lexapro
[Experimental model of depression: neurochemical changes and the effects of imipramine and citalopram]

[Article in Russian]

Kudriavtseva NN, Bakshtanovskaia IV, Madorskaia IA, Popova NK, Marona-Lewicka D, Vetulani I.

A study was made of the influence of the antidepressants imipramine and citalopram (10 mg/kg, chronic administration, i.p.) on the depression-like condition in submissive male rats. The above condition developed under the effect of chronic emotional stress because of successive experience of defeat in social confrontations (Kudryavtseva, Bakshtanovskaya, 1988). Imipramine rather than citalopram exerted a remarkable antidepressive effect recorded by the Porsolt's test. Measurements of the content of serotonin, dopamine and noradrenaline in brain structures have demonstrated changes in the serotoninergic and catecholaminergic systems in males with the depressive symptomatology in relation to intact animals. It should be mentioned that at different stages of pathological process formation, the role of certain structures and mediator systems underwent definite changes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1319631&dopt=Abstract citalopram escitalopram Lexapro