citalopram Celexa
Effect of subchronic lithium treatment on citalopram-induced increases in extracellular concentrations of serotonin in the medial prefrontal cortex.

Muraki I, Inoue T, Hashimoto S, Izumi T, Ito K, Koyama T.

Department of Psychiatry, Hokkaido University School of Medicine, Sapporo, Japan. smuraki mtj.biglobe.ne.jp

We investigated the effect of citalopram [a selective serotonin (5-HT) reuptake inhibitor; SSRI] and MKC-242 (a selective 5-HT1A agonist), following treatment with subchronic lithium (p.o., 1 week) on extracellular 5-HT concentrations in the medial prefrontal cortex (mPFC). Acute treatment with citalopram (3 and 30 mg/kg) led to significant increases in extracellular 5-HT concentrations. The subchronic lithium group showed significantly higher basal levels of extracellular 5-HT than normal diet controls. Acute citalopram (3 and 30 mg/kg) treatment together with subchronic lithium treatment showed significant increases in the extracellular 5-HT concentrations, compared with citalopram treatment alone. Acute MKC-242 (1 mg/kg) treatment showed significant decreases in extracellular 5-HT concentrations, in both the normal diet and lithium diet groups to the same extent. The addition of lithium did not change the effect of the 5-HT1A agonist on extracellular 5-HT concentrations. This study suggests that lithium augmentation of the antidepressant effect of SSRI is mediated by the additional increases in extracellular 5-HT concentrations following the co-administrations of lithium and SSRI.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11208912&dopt=Abstract citalopram Celexa



citalopram Celexa
Pharmacological characterisation of the decrease in 5-HT synthesis in the mouse brain evoked by the selective serotonin re-uptake inhibitor citalopram.

Stenfors C, Yu H, Ross SB.

AstraZeneca R&D Sodertalje, Bioscience, Sweden.

The selective serotonin re-uptake inhibitor (SSRI) citalopram decreases the synthesis of 5-hydroxytryptamine (5-HT) in the mouse brain in vivo. The underlying mechanism was studied by recording the accumulation of 5-hydroxytryptophan (5-HTP) in hypothalamus and hippocampus after inhibition of the aromatic amino acid decarboxylase activity with m-hydroxybenzylhydrazine (NSD 1015). Depletion of 5-HT with reserpine markedly reduced the citalopram-induced decrease of 5-HTP but not that evoked by the 5-HT1A receptor agonist 8-OH-DPAT, which indicates that the presence of endogenous 5-HT is necessary for full effect of citalopram. In contrast to the almost complete antagonism of the decrease in 5-HT synthesis induced by 8-OH-DPAT, the 5-HT1A receptor antagonist WAY-100,635 only slightly affected the citalopram-evoked decrease in 5-HT synthesis. Likewise, the 5-HT1B receptor antagonists NAS-181 and GR127935 only slightly antagonised the citalopram effect although they strongly inhibited the decrease in 5-HT synthesis induced by the 5-HT1B receptor agonist anpirtoline. Combined treatment with 5-HT1A and 5-HT1B receptor antagonists did not produce any additive antagonistic effect on the citalopram-induced decrease in 5-HT synthesis. The 5-HT2A/2C receptor antagonist ketanserin, the 5-HT3 receptor antagonist ondansetron and the 5-HT4 receptor antagonist RS-39604 had no effect on the citalopram-induced decrease in 5-HT synthesis. The same was found for several other non-selective 5-HT receptor antagonists, e.g. cyproheptadine, dihydroergotamine, methiothepin, methysergide, metergoline and mianserin. It is concluded that the citalopram-induced decrease in 5-HT synthesis differs in sensitivity from that mediated by 5-HT1A or 5-HT1B receptor agonists and citalopram also seems to require endogenous 5-HT for its full effect.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11218075&dopt=Abstract citalopram Celexa



citalopram Celexa
Liquid-phase microextraction and capillary electrophoresis of citalopram, an antidepressant drug.

Halvorsen TG, Pedersen-Bjergaard S, Rasmussen KE.

School of Pharmacy, University of Oslo, Norway. t.g.halvorsen farmasi.uio.no

A newly developed disposable device for liquid-phase microextraction (LPME) was evaluated for the capillary electrophoresis (CE) of the antidepressant drug citalopram (CIT) and its main metabolite N-desmethylcitalopram (DCIT) in human plasma. CIT and DCIT were extracted from 1 ml plasma samples through hexyl ether immobilised in the pores of a porous polypropylene hollow fibre and into 25 microl of 20 mM phosphate buffer (pH 2.75) present inside the hollow fibre (acceptor phase). Prior to extraction, the samples were made strongly alkaline in order to promote LPME of the basic drugs. Owing to the high ratio between the volumes of sample and acceptor phase, and owing to high partition coefficients, CIT and DCIT were enriched by a factor of 25 to 30. In addition, sample clean-up occurred during LPME since salts, proteins and the majority of endogenic substances were unable to penetrate the hexyl ether layer. Since the extracts were aqueous, they were injected directly into the CE instrument. Limits of quantification (S/N= 10) for CIT and DCIT in plasma were 16.5 ng/ml and 18 ng/ml respectively, while the limits of detection (S/N=3) were 5 ng/ml and 5.5 ng/ml respectively. This enabled CIT (and DCIT) to be analysed within the therapeutic range by LPME-CE and detection limits were comparable with previously reported HPLC methods.

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citalopram Celexa
Effect of serotonin reuptake inhibitor on syndrome development in obese hyperglycemic mice (Umea ob/ob).

Thrybom T, Rooth P, Lindstrom P.

Department of Integrative Medical Biology, Umea University, Sweden.

These experiments tested the effect of 10 to 30 mg, citalopram/kg body weight on food intake, weight increase, and blood glucose levels in young obese hyperglycemic mice (Umea ob/ob). A leptin defect in ob/ob mice results in hyperphagia, hyperglycemia, and increased body weight compared with normal mice. Citalopram had no effect on weight increase in ob/ob mice aged 3 to 10 weeks, when the weight increase is most rapid. Citalopram reduced the weight increase at the age 10 to 19 weeks. Food intake reaches a maximum at age 7 to 10 weeks and then decreases. The reduction was more rapid in citalopram-treated mice. The weight of feces paralleled the food intake. Citalopram treatment had no effect on serum insulin levels in 15-week-old mice. Blood sugar values in fed mice reached a peak at age 7 weeks (21.7 +/- 1.7 mmol/L in controls and 22.3 +/- 1 mmol/L in citalopram-treated mice). After that, blood sugar values decreased. The decrease was more pronounced in citalopram-treated mice (P < .01 compared with controls). Blood glucose levels were lower at ages 12 to 15 weeks in female ob/ob control mice (13.6 +/- 2.5 mmol/L v 19.0 +/- 0.6 mmol/L in male control mice; P < .05). The effect of citalopram was the same in male and female mice. There was a close correlation between accumulated food intake and blood glucose values in individual animals. At age 3 to 10 weeks, ob/ob mice have a high beta-cell proliferation rate, and they have large islets of Langerhans. This was not affected by citalopram treatment. Our findings show that the serotonergic system plays a role as a regulator of food intake over shorter periods, and this is also true in the absence of leptin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11229420&dopt=Abstract citalopram Celexa



citalopram Celexa
Acute and chronic effects of citalopram on postsynaptic 5-hydroxytryptamine(1A) receptor-mediated feedback: a microdialysis study in the amygdala.

Bosker FJ, Cremers TI, Jongsma ME, Westerink BH, Wikstrom HV, den Boer JA.

Department of Psychiatry, Academic Hospital Groningen, the Netherlands. f.bosker acggn.azg.nl

Microdialysis was used to assess the involvement of postsynaptic 5-hydroxytryptamine(1A) (5-HT(1A)) receptors in the regulation of extracellular 5-HT in the amygdala. Local infusion of the 5-HT(1A) receptor agonist flesinoxan (0.3, 1, 3 microM) for 30 min into the amygdala maximally decreased 5-HT to 50% of basal level. Systemic administration of citalopram (10 micromol/kg) increased 5-HT to 175% of basal level. Local infusion of 1 microM of the 5-HT(1A) receptor antagonist WAY 100.635 into the amygdala augmented the effect of citalopram to more than 500% of basal 5-HT level. 5-HT(1A) receptor responsiveness after chronic citalopram treatment was determined in two ways. First, by local infusion of 1 microM flesinoxan for 30 min into the amygdala, which showed a significant 63% reduction in response (area under the concentration-time curve; AUC) for the citalopram group compared to the saline group. Second, by systemic administration of citalopram (10 micromol/kg), which increased 5-HT to 350% of basal level. The effect was larger than in untreated animals, but more important, local infusion of 1 microM WAY 100.635 into the amygdala now failed to augment the effect of citalopram. Both the flesinoxan and WAY 100.635 data suggest an involvement of postsynaptic 5-HT(1A) receptor-mediated feedback in the amygdala, which diminishes following chronic citalopram treatment.

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citalopram Celexa
Following long-term training with citalopram, both mirtazapine and mianserin block its discriminative stimulus properties in rats.

Dekeyne A, Iob L, Millan MJ.

Institut de Recherches Servier, Centre de Recherches de Croissy, Psychopharmacology Department, Croissy-sur-Seine, Paris, France. anne.dekeyne fr.netgrs.com

RATIONALE: The discriminative stimulus (DS) properties of the selective serotonin (5-HT) uptake inhibitor (SSRI), citalopram, are mediated by 5-HT2C receptors. Interestingly, the "atypical" antidepressants, mianserin and mirtazapine, behave as antagonists at 5-HT2C receptors. OBJECTIVE: Herein, we evaluated the influence of mianserin and mirtazapine upon the DS effects of citalopram. METHODS: In a two-lever drug discrimination procedure, rats initially trained to discriminate citalopram (2.5 mg/kg, i.p.) from saline were retrained with a lower dose of citalopram (0.63 mg/kg, i.p.). Subsequently, generalization and antagonist studies were conducted with mianserin and mirtazapine. RESULTS: Both dose-dependently blocked, but did not generalize to, the DS properties of citalopram without markedly disrupting response rates. Their effective dose50s were 0.1 and 1.4 mg/kg, s.c., respectively. CONCLUSION: These observations are consistent with a role of 5-HT2C receptors in mediation of the interoceptive properties of SSRIs and suggest that the DS effects of citalopram are not related to its "antidepressant" properties per se. Finally, they underline the distinctive nature of mirtazapine and mianserin as compared to antidepressant agents which interact with 5-HT uptake sites.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11271412&dopt=Abstract citalopram Celexa



citalopram Celexa
Differential effects of fluoxetine and citalopram treatments on serotonin 5-HT(2C) receptor occupancy in rat brain.

Palvimaki EP, Kuoppamaki M, Syvalahti E, Hietala J.

Department of Pharmacology and Clinical Pharmacology, Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland.

Ex vivo receptor occupancy measurements were performed in order to study the effects of the serotonin reuptake inhibitors fluoxetine and citalopram on serotonin 5-HT(2C) receptors. To determine the degree of 5-HT(2C) receptor occupancy, [(3)H]mesulergine binding in brain sections containing rat choroid plexus was measured at various time-points after drug injection. For comparison, [(3)H]ketanserin binding to frontal cortex 5-HT(2A) receptors was measured. Fluoxetine treatments (10 and 20 mg/kg) resulted in 5-HT(2C) receptor occupancy of up to 25 and 43%, respectively. Fluoxetine (20 mg/kg) caused a persistent effect: at the 24 h time-point, 23% of 5-HT(2C) receptors were still occupied. Citalopram treatment did not result in marked 5-HT(2C) receptor occupancy. Neither drug caused significant 5-HT(2A) receptor occupancy. In conclusion, the results demonstrate pharmacodynamic differences between fluoxetine and citalopram at the level of 5-HT(2C) receptors. These findings provide evidence that direct occupancy of 5-HT(2C) receptors may contribute to the mechanism of action of fluoxetine.

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citalopram Celexa
Costs and outcomes of use of amitriptyline, citalopram and fluoxetine in major depression: exploratory study.

Hosak L, Tuma I, Hanus H, Straka L.

Department of Psychiatry, Charles University in Prague, Faculty of Medicine in Hradec Kralove. hosak lfhk.cuni.cz

BACKGROUND: The increasing cost of pharmaceuticals in the Czech Republic has led to the restriction on prescriptions of expensive new antidepressants. The aim of the study was to compare the costs and outcomes of using amitriptyline, citalopram and fluoxetine in the treatment of major depression. METHODS: Ninety patients (69 women) with a mean age of 44.5 years (S.D. = 14.3) suffering from major depression were treated with amitriptyline (N = 31), citalopram (N = 29) and fluoxetine (N = 30). Direct medical costs and effectiveness (indicated by the number of hospitalization-free days) were assessed in a prospective, open, intent-to-treat study. RESULTS: Neither cost nor effectiveness were significantly different among the treatment groups. CONCLUSION: Amitriptyline treatment is not less expensive nor more effective than citalopram or fluoxetine therapies. There is no advantage in restricting patients from treatment with SSRIs, which have fewer adverse effects and a decreased risk of a lethal overdosage in comparison with tricyclic antidepressants.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11294131&dopt=Abstract citalopram Celexa