citalopram Celexa
Hormone responses to citalopram in abstinent alcohol dependent subjects.

Gotjen D, Szabo Z, Lee S, Wand G.

Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

BACKGROUND: The integrity of serotonin neurotransmission may be important in reducing risk for alcoholism and in preventing relapse to alcohol dependence. There are several lines of evidence suggesting that alcohol dependent persons have an altered and/or injured serotonin system. The purpose of this study was to examine ACTH, cortisol, and prolactin responses to the selective serotonin reuptake inhibitor (SSRI), citalopram, as a function of personal or family history of alcohol dependence in a group of abstinent alcohol dependent men. METHODS: Twelve healthy, abstinent male participants who met diagnostic criteria for a history of alcohol dependence but not for other Axis I disorders were included in the study (mean years abstinent, 3.5 +/- 3.7; mean years of dependent drinking, 15.2 +/- 6.9). Fourteen healthy volunteers served as control subjects. Controls did not meet the DSM-IV diagnostic criteria for any Axis I disorders and history of drug or alcohol abuse or dependence. All subjects were also characterized by the presence or absence of family history of alcoholism validated by collateral interviews. RESULTS: ACTH responses to citalopram were minimally faster in abstinent alcohol dependent men compared to controls. However, cortisol and prolactin responses to citalopram did not differ by personal or family history of alcohol dependence. There was no correlation between hormone responses and the duration of abstinence from alcohol; between hormone responses and the years of dependent drinking and between hormone responses and NEO Personality Inventory scores. CONCLUSION: By probing the functional capacity of the serotonin system with citalopram, we did not detect physiologically relevant hormone differences between abstinent alcohol dependent men and controls.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12436050&dopt=Abstract citalopram Celexa



citalopram Celexa
[11C]-DASB, a tool for in vivo measurement of SSRI-induced occupancy of the serotonin transporter: PET characterization and evaluation in cats.

Ginovart N, Wilson AA, Meyer JH, Hussey D, Houle S.

PET Centre, Centre for Addiction and Mental Health and University of Toronto, Toronto, Ontario M5T 1R8, Canada. nginovart camhpet.on.ca

The in vivo pharmacological profile of [(11)C]-DASB, a new radioligand developed for in vivo imaging of the serotonin transporter (SERT), was evaluated in the cat brain using positron emission tomography (PET). The in vivo distribution of [(11)C]-DASB binding was consistent with the known distribution of SERT sites in the cat brain in vitro with high uptakes of radioactivity in the midbrain and thalamus, intermediate levels in striatum, and modest to low levels of radioactivity in the neocortex and cerebellum, respectively. [(11)C]-DASB binding potential (BP) values ranged from about 0.2 in the neocortex to 2.2 in the midbrain. Radioligand binding in all brain regions except cerebellum was markedly reduced following pretreatment with fluoxetine and citalopram, but was unaffected by pretreatment with GBR12909, maprotiline, and haloperidol, indicating specificity of [(11)C]-DASB binding to the SERT. Two cats were each examined using PET and [(11)C]-DASB in a longitudinal fashion (from 30 min and up to 24 days) following a single i.v. dose of: 1) fluoxetine, and 2) citalopram at different dosages. Both drugs induced similar degrees of SERT occupancy at 30 min postinjection (approximately 90%). A comparison of citalopram and fluoxetine pharmacokinetics in the same animal and at the same dosage (1 mg/kg) showed that citalopram SERT occupancy and plasma half-lives were 9 times and 14 times shorter, respectively, than those of fluoxetine and norfluoxetine. In addition, studies performed after injection of the monoamine oxidase inhibitor tranylcypromine suggested that high levels of synaptic serotonin may compete with [(11)C]-DASB for binding on the SERT. These studies indicate that [(11)C]-DASB is a suitable PET radioligand for measuring drug occupancy of the SERT in vivo and has potential for monitoring in vivo changes in serotonin levels. Copyright 2002 Wiley-Liss, Inc.

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citalopram Celexa
Pentylenetetrazol-kindling of seizures selectively decreases [3H]-citalopram binding in the CA-3 area of rat hippocampus.

Szyndler J, Wierzba-Bobrowicz T, Maciejak P, Siemiatkowski M, Rok P, Lehner M, Czlonkowska AI, Bidzinski A, Wislowska A, Zienowicz M, Plaznik A.

Department of Experimental and Clinical Pharmacology, Medical University, 26/28 Krakowskie Przedmiescie Street, 00-927 Warsaw, Poland.

The present study was aimed at determining the changes in the 5-HT transporter activity, in different brain structures after pentylenetetrazol induced kindling of seizures. We examined [3H]-citalopram binding in the rat brain structures, and the neurodegenerative effects in the hippocampal formation using autoradiographic and immunohistochemical methods. A statistically significant and selective reduction in the binding of [3H]-citalopram was found in the CA3 field of the hippocampus (P=0.009), and a similar tendency, close to the significance level, in the dentate gyrus (P=0.05). This effect was accompanied by a loss of neurons and activation of microglia in the hippocampal formation. The present data suggest the important role for CA3- serotonergic innervation in pentylenetetrazol induced kindling of seizures.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12457739&dopt=Abstract citalopram Celexa



citalopram Celexa
Citalopram for the treatment of adolescent anxiety disorders: a pilot study.

Prince JB, Bostic JQ, Monuteaux M, Brown K, Place S.

Department of Child Psychiatry, Harvard Medical School, Boston, Mass, USA. Jprince partners.org

Charts of 17 adolescent patients treated naturalistically with citalopram for various anxiety disorders were reviewed. Patients were retrospectively assessed using the Clinical Global Impression (CGI)-Severity scale at the beginning and end of treatment. Eighty-two percent (14/17) of patients were rated as much or very much improved on the CGI-Improvement scale after treatment with citalopram. Patients were treated for an average of 156-/+85.1 days at a mean dose of 32.3-/+18.5 mg/day of citalopram. Fifty-three percent (9/17) of this sample had previous exposure to alternative selective serotonin reuptake inhibitors, and 89% (8/9) of those patients responded positively to citalopram. Citalopram appeared well tolerated, with only one patient discontinuing treatment due to side effects. In this naturalistic setting, citalopram appeared to be a well-tolerated and effective treatment for a range of anxiety disorders in adolescents.

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citalopram Celexa
Chronic citalopram treatment induces time-dependent changes in the expression and DNA-binding activity of transcription factor AP-2 in rat brain.

Berggard C, Damberg M, Oreland L.

Department of Neuroscience, Unit of Pharmacology, Uppsala University, PO Box 593 BMC, SE-751 24, Uppsala, Sweden.

Imbalances in the midbrain monoaminergic systems have been implicated to play a role in neuropsychiatric conditions. Several genes in these systems have binding sites for transcription factor activating protein-2 (AP-2) in their regulatory regions. Thus, AP-2 may be a factor controlling the expression of genes in the monoaminergic systems important for maintaining normal psychiatric functions. The present study indicates that subchronic treatment with the antidepressant citalopram induces time-dependent changes in DNA-binding activity and levels of transcription factor AP-2 in rat whole brain. Rats were treated with citalopram (10 mg/kg) for 1, 3, 7 and 21 days. Animals treated for 7 days had significantly decreased DNA-binding activity and levels of AP-2 alpha and AP-2 beta isoforms when compared to saline-treated animals. There was no observed difference between citalopram- and saline-treated animals after 21 days. Elucidation of the molecular mechanisms underlying mental disorders is important for future drug development, where transcription factors might be important drug targets.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12480117&dopt=Abstract citalopram Celexa



citalopram Celexa
Local, but not systemic, administration of serotonergic antidepressants decreases hippocampal nitric oxide synthase activity.

Wegener G, Volke V, Harvey BH, Rosenberg R.

Institute for Basic Psychiatric Research, Department of Biological Psychiatry, Skovagervej 2, DK-8240 Risskov, Denmark. wegener dadlnet.dk

Nitric oxide (NO) is an unconventional transmitter molecule in the nervous system, synthesized by nitric oxide synthase (NOS) following activation of the N-methyl-D-aspartate (NMDA) receptor. Several in vivo studies have demonstrated that NO modulates the extracellular levels of various neurotransmitters in the central nervous system, while serotonin (5-HT) re-uptake may be influenced by the NO pathway. Moreover, inhibitors of NOS exhibit antidepressant-like and anxiolytic-like properties in various animal models. Therefore, the aims of the present study were to clarify the involvement of distinct antidepressants acting on the serotonin re-uptake site in the regulation of the activity of hippocampal NOS in vitro, in vivo and ex vivo. We found that citalopram, paroxetine, imipramine and N(G)-nitro-L-arginine dose dependently decreased the hippocampal NOS activity in vitro. Moreover, local administration of citalopram, paroxetine, tianeptine, imipramine and N(G)-nitro-L-arginine significantly decreased the hippocampal NOS activity in vivo at a concentration significantly lower than in vitro. No effect on NOS activity following retrodialysis with 5-HT was observed. Acute (5 mg/kg, s.c.) and chronic (3 weeks, 20 mg/kg/24 h) systemic administration of citalopram did not influence NOS activity ex vivo. The effects on NOS represent a response to structurally dissimilar serotonergic antidepressants. However, since these data reflect effects on basal NOS activity, we believe that serotonergic antidepressants do not directly affect NOS at dosages used clinically, but the findings may reflect a secondary action of antidepressants on the glutamate NMDA receptor following their primary inhibitory action at the 5-HT transporter.

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citalopram Celexa
Tricyclic antidepressants prevent the differentiation of monocytes into macrophage-like cells in vitro.

Ying G, Karlsson H, DePierre JW, Nassberger L.

Department of Biochemistry, Unit for Biochemical Toxicology, Stockholm University, Stockholm, Sweden.

The investigation was designed to determine whether the two tricyclic antidepressant agents (TCAs) clomipramine and imipramine and the selective reuptake inhibitor citalopram affect differentiation of human monocytes to macrophage-like cells (MAC-LCs). We established primary adherent cultures of peripheral blood monocytes and monitored their morphology, capacity for phagocytosis and antigen expression during transformation to MAC-LCs. As expected, maturation of monocytes to MACs is accompanied by changes in morphology, elevated expression of the antigens CD16 and CD51 and an increase in the percentage of phagocytic cells. Treatment of cells with the TCAs clomipramine (40 micromol/L) or imipramine (100 micromol/L) and with citalopram (100 micromol/L), for 11 days resulted in the following observations: (1) monocytes treated with TCAs never developed the morphology characteristic of the MAC-LCs; (2) TCAs reduced the percentage of phagocytic cells; (3) TCAs had little influence on the expression of CD14, CD16, CD51, and HLA-DR. However, when added after monocyte differentiation into MAC-LCs, citalopram and clomipramine no longer reduced the percentage of phagocytic cells and these effects were not simply due to irreversible cytotoxicity. Thus clomipramine, imipramine, and citalopram inhibit differentiation of human monocytes into MAC-LCs in vitro, but in a reversible manner.

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citalopram Celexa
Simultaneous quantification of citalopram, clozapine, fluoxetine, norfluoxetine, maprotiline, desmethylmaprotiline and trazodone in human serum by HPLC analysis.

Waschgler R, Hubmann MR, Conca A, Moll W, Konig P.

Medical Central Laboratory, Feldkirch, Austria. rwaschgler mzl.at

We describe an analytical procedure for the simultaneous quantification of citalopram (seropram), clozapine (leponex), fluoxetine (fluctine), norfluoxetine, maprotiline (ludiomil), desmethylmaprotiline and trazodone (trittico) in human serum within a period of 11.5 minutes using reversed phase HPLC. After 2 liquid/liquid extractions in the sample preparation phase, the drugs and metabolites were separated on a C18 column using a mobile phase consisting of acetonitrile/buffer (30/70, v:v) at 70 degrees C, a flow rate of 1.5 m/min and haloperidol as internal standard. Absorption and native fluorescence signals of the eluted compounds were detected simultaneously at 260 nm and 227/300 nm (excitation/emission), respectively. The calibration ranges for citalopram, clozapine, fluoxetine, norfluoxetine, maprotiline, and desmethylmaprotiline ranged from 50-400 microg/l and for trazodone from 50-3,200 microg/l. The CVs varied between 0.6% and 5.5% (within-run) and between 3.2% and 7.1% (between-run). Recoveries were > 90% for all pharmaceuticals. We noticed no interferences from several commonly used drugs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12503813&dopt=Abstract citalopram Celexa