citalopram escitalopram Lexapro
Steady-state pharmacokinetics of the enantiomers of citalopram and its metabolites in humans.

Sidhu J, Priskorn M, Poulsen M, Segonzac A, Grollier G, Larsen F.

Department of Pharmacokinetics/Dynamics, H. Lundbeck A/S, Copenhagen, Denmark.

The steady-state pharmacokinetics in serum and urine of the enantiomers of citalopram and its metabolites, demethylcitalopram (DCT) and didemethylcitalopram (DDCT), were investigated after multiple doses of rac-citalopram for 21 consecutive days (40 mg per day) to healthy human subjects who were extensive metabolisers of sparteine and mephenytoin. Comparable pharmacokinetic variability was noted for (+)-(S)-, (-)-(R)- and rac-citalopram. Enantiomeric (S/R) serum concentration ratios for citalopram were always less than unity and were constant during the steady-state dosing interval. A modest, but statistically significant, stereoselectivity in the disposition of citalopram and its two main metabolites was observed. Serum levels of the (+)-(S)-enantiomers of citalopram, DCT, and DDCT throughout the steady-state dosing interval investigated were 37 +/- 6%, 42 +/- 3% and 32 +/- 3%, respectively, of their total racemic serum concentrations. The (+)-(S)-enantiomers of citalopram, DCT, and DDCT were eliminated faster than their antipodes. For (-)-(R)- and (+)-(S)-citalopram, respectively, the serum t1/2 averaged 47 +/- 11 and 35 +/- 4 h and AUCss averaged 4,193 +/- 1,118 h.nmol/l and 2,562 +/- 1,190 h.nmol/l. The observed enantiospecificities were apparently more related to clearance, rather than to distributional mechanisms.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9366029&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Solid-phase extraction with end-capped C2 columns for the routine measurement of racemic citalopram and metabolites in plasma by high-performance liquid chromatography.

Carlsson B, Norlander B.

Department of Clinical Pharmacology, Faculty of Health Sciences, Linkoping University, Sweden.

An assay based on solid-phase extraction followed by high-performance liquid chromatography (HPLC) was developed for the measurement of citalopram and its main metabolites desmethylcitalopram and didesmethylcitalopram. The best extraction procedure was performed with end-capped C2 column utilising secondary silanol interactions to obtain clean extract. The HPLC analysis was done on a phenyl column with a mobile phase without any amine additives. Fluorescence detection gave a limit of detection of 0.8 nmol/l plasma for the compounds analysed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9449577&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
High-performance liquid chromatography method for analyzing citalopram and desmethylcitalopram from human serum.

Akerman KK, Jolkkonen J, Huttunen H, Penttila I.

Department of Clinical Chemistry, Kuopio University Hospital, Finland.

This report describes a sensitive and specific method for analyzing a serotonin reuptake blocker, citalopram, and its active metabolite, desmethylcitalopram, in human serum. For high-performance liquid chromatography (HPLC) analysis, samples and standards are prepared with ASPEC automatic sample preparator using 100 mg Bond-Elut C-18 solid-phase extraction columns. The method is an isocratic HPLC method with a mobile phase of acetonitrile:methanol:50 mM dipotassium hydrogenphosphate, pH 4.7 (40:100). Detection is performed with diode array detector at 220 nm and the peak purity analyses at 210 to 365 nm. The intraassay coefficient of variation ranges from 3.7% to 7.3%, and the interassay coefficient of variation ranges from 6.9% to 9.9% at therapeutic drug concentrations. The detection limit is 15 nmol/l. The method is suitable for therapeutic drug monitoring in a clinical laboratory. A clear correlation, r = 0.72 (y = 0.36x + 17.94), between citalopram and its metabolite levels is observed in routine therapeutic drug monitoring service. A linear correlation between serum concentration and daily dose of citalopram in patient groups is also observed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9485550&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Apomorphine-induced aggressiveness and [3H]citalopram binding after antidepressant treatment in rats.

Matto V, Allikmets L, Skrebuhhova T.

Department of Pharmacology, University of Tartu, Estonia.

The effects of acute and repeated administration of antidepressive drugs on apomorphine-induced aggressive behavior and [3H]citalopram binding were studied. In acute behavioral experiments with apomorphine pretreated (1.0 mg/kg, once daily) animals, desipramine (10 mg/kg) and clomipramine (10 mg/kg) enhanced, buspirone (2.5 and 5.0 mg/kg) completely blocked, but fluoxetine, amitriptyline, imipramine (10 mg/kg), and citalopram (10 and 20 mg/kg) had no effect on the intensity of aggressive behavior. Repeated concomitant apomorphine (1.0 mg/kg) and citalopram (10 mg/kg) administration reduced the affinity (Kd) of the 5-HT transporter binding sites in three brain regions. This finding was confirmed by an additional experiment as the effect of citalopram treatment. Repeated apomorphine (1.0 mg/kg) or apomorphine (1.0 mg/kg) plus desipramine (10 mg/kg) treatment had no unidirectional effect on Kd, the maximal number of apparent binding sties (Bmax) was unchanged in all experiments. Our study indicates that the 5-HT reuptake blockade has no major influence on the apomorphine-induced aggressive behavior, but the 5-HT1A receptor subtype may be involved in the mediation of the aggressive behavior in this paradigm.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9512081&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Basal and stimulated extracellular serotonin concentration in the brain of rats with altered serotonin uptake.

Romero L, Jernej B, Bel N, Cicin-Sain L, Cortes R, Artigas F.

Department of Neurochemistry, Instituto de Investigaciones Biomedicas de Barcelona, CSIC, Spain.

We examined the relationship between the density of serotonergic (5-hydroxytryptamine [5-HT]) uptake sites and extracellular 5-HT concentration in the rat brain using microdialysis with two different models, lesions with 5,7-dihydroxytryptamine (50 microg in the dorsal raphe nucleus (DRN) 15 days before) and sublines of rats genetically selected displaying extreme values of platelet 5-HT uptake. Compared to controls, lesioned rats had a reduced cortical concentration of 5-hydroxyindoles (45%), unchanged basal extracellular 5-HT in the DRN and ventral hippocampus (VHPC), and reduced basal 5-hydroxyindoleacetic acid (5-HIAA) concentrations (46%, DRN; 22%, VHPC). Yet the perfusion of 100 mmol/L KCl or 1 micromol/L citalopram elevated dialysate 5-HT significantly more in the DRN and VHPC of controls. In genetically selected rats, platelet 5-HT content and uptake were highly correlated (r2 = 0.9145). Baseline dialysate 5-HT (VHPC) was not different between high and low 5-HT rats and from normal Wistar rats. However, KCl or citalopram perfusion increased dialysate 5-HT significantly more in high 5-HT than in low 5-HT rats, and the former displayed a greater in vivo tissue 5-HT recovery. Significant but small differences in the same direction were noted in [3H]citalopram binding in several brain areas, as measured autoradiographically. Thus, basal extracellular 5-HT (but not 5-HIAA) concentrations are largely independent on the density of serotonergic innervation and associated changes in uptake sites. However, marked differences emerge during axonal depolarization or reuptake blockade. The significance of these findings for the treatment of mood disorders in patients with neurological disorders is discussed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9517840&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Adaptation of cortical NMDA receptors by chronic treatment with specific serotonin reuptake inhibitors.

Nowak G, Legutko B, Skolnick P, Popik P.

Institute of Pharmacology, Polish Academy of Sciences, Smetna, Krakow.

Glycine displaces [3H]CGP-39653 ([3H]D,L-(E)-2-amino-4-propyl-5-phosphono-3-pentenoic acid) binding to the glutamate recognition site with both high and low affinity. We reported previously that chronic treatment with antidepressants reduced the proportion of high to low affinity sites, or, even eliminated the high affinity sites in case of citalopram. Here, we compared the effects of citalopram with another serotonin specific reuptake inhibitor, fluoxetine on this measure. Chronic administration of citalopram or fluoxetine eliminated high affinity glycine-displaceable [3H]CGP-39653 binding to the mouse cortex in 78 and 56% of animals, respectively, indicating that selective serotonin reuptake inhibitors produce qualitatively similar adaptive changes at NMDA receptors, that differ from other antidepressants in this neurochemical measure.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9548410&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Selective serotonin reuptake inhibitors potentiate 8-OH-DPAT-induced stimulus control in the pigeon.

Wolff MC, Leander JD.

Lilly Research Laboratories, Eli Lilly, Lilly Corporate Center, Indianapolis, IN 46285, USA.

The effects of two selective serotonin reuptake inhibitors, fluoxetine and citalopram, and a nonselective monoamine reuptake inhibitor, imipramine, were characterized in pigeons that had been trained to discriminate 0.64 mg/kg of 8-hydroxy-(2-di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), a 5-HT1A receptor agonist, from saline. Neither fluoxetine, citalopram, nor imipramine generalized to the 8-OH-DPAT-induced stimulus cue. However, when administered in addition to 8-OH-DPAT, both fluoxetine (10 mg/kg) and citalopram (10 mg/kg) lowered the ED50 for generalization of 8-OH-DPAT from 0.16 mg/kg (8-OH-DPAT by itself) to 0.05 mg/kg (fluoxetine + 8-OH-DPAT) and 0.06 mg/kg (citalopram + 8-OH-DPAT). Under similar conditions, imipramine (1 mg/kg) had no effect on the generalization curve for 8-OH-DPAT. The data support the hypothesis that activation of the 5-HT1A receptor may be relevant to the mechanism of action of serotonin reuptake inhibitors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9593591&dopt=Abstract citalopram escitalopram Lexapro