citalopram escitalopram Lexapro
(-)-Pindolol, but not buspirone, potentiates the citalopram-induced rise in extracellular 5-hydroxytryptamine.

Hjorth S.

Department of Pharmacology, University of Goteborg, Sweden. stephan.hjorth pharm.gu.se

Recent open clinical studies suggest that pindolol and buspirone may enhance the efficacy and/or shorten the latency to antidepressant action of selective serotonin reuptake inhibitors (SSRI) in unipolar major depressive disorder. The present investigation addressed the possibility that these agents share the ability to enhance the extracellular 5-hydroxytryptamine (5-HT)-elevating response to the SSRI citalopram. For the purpose, in vivo microdialysis in the rat ventral hippocampus was employed. (-)-Pindolol (8 mg/kg s.c.) augmented the citalopram (5 mg/kg s.c.)-induced rise of extracellular 5-HT levels, whereas buspirone (5 mg/kg s.c.) failed to do so. This effect of (-)-pindolol probably reflects its ability to block 5-HT1A autoreceptors, thereby abating the citalopram-induced indirect activation of these sites (secondary to the inhibition of 5-HT reuptake and elevation of extracellular 5-HT in the midbrain raphe). The lack of effect of buspirone in this model indicates that the clinically observed antidepressant augmentation action of buspirone is not mediated indirectly, via enhanced extracellular levels of 5-HT.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8813565&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Efficacy of citalopram as a monotherapy or as an adjunctive treatment to estrogen therapy for perimenopausal and postmenopausal women with depression and vasomotor symptoms.

Soares CN, Poitras JR, Prouty J, Alexander AB, Shifren JL, Cohen LS.

Perinatal and Reproductive Psychiatry Clinical Research Program, Massachusetts General Hospital and the Department of Psychiatry, Harvard Medical School, Boston, 02114, USA. csoares partners.org

BACKGROUND: Women frequently report depressive and vasomotor symptoms during the menopausal transition. Hormone therapy has been shown to improve some of these symptoms, although its safety as a long-term treatment has been questioned. It is still unclear whether the use of antidepressants alone may alleviate menopause-related mood and vasomotor symptoms or enhance the response observed with short-term use of estrogen therapy. METHOD: Perimenopausal and postmenopausal women with depressive disorders (DSM-IV criteria) and menopause-related symptoms received treatment with 20 to 60 mg/day of citalopram alone (N = 22) or adjunctive to estrogen therapy (N = 13). Adjunctive treatment was offered to subjects who had failed to show remission of depression after 4 weeks with estrogen therapy (estradiol [E(2)]) alone. Depressive symptoms, menopause-related symptoms, and global clinical improvement were assessed at baseline and at endpoint of adjunctive treatment (8 weeks) or citalopram monotherapy (12 weeks). Remission of depression was defined as a score of < 10 on the Montgomery-Asberg Depression Rating Scale and a score of < or = 2 on the Clinical Global Impressions scale at endpoint. Data were collected from November 2000 to February 2002. RESULTS: Twelve women (92.3%) concluded the 8-week adjunctive treatment; 11 subjects (91.6%) achieved full remission of depression. Symptoms that had persisted after an initial 4-week treatment with E(2) alone (e.g., tension, anxiousness, tiredness, and difficulty in concentrating) improved significantly (p <.05). Fifteen subjects concluded the treatment with citalopram monotherapy; 13 subjects (86.6%) showed full remission of depression. Anxiety and other somatic complaints had significant improvement (p <.05), while there was a trend toward improvement in vasomotor symptoms in those receiving monotherapy (p =.06). CONCLUSION: Citalopram alone is an efficacious treatment for perimenopausal and postmenopausal women with depression. Citalopram also appears to be efficacious as an adjunctive treatment for depressed subjects who remain symptomatic after treatment with E(2) (i.e., E(2) nonremitters). The role of citalopram monotherapy for the management of vasomotor symptoms warrants further investigation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12716252&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Chronic citalopram and fluoxetine treatments upregulate 5-HT2c receptors in the rat choroid plexus.

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

Department of Pharmacology, University of Turku, Finland.

The effects of chronic (for 14 days) citalopram and fluoxetine treatments with three doses (2.5, 10, and 20 mg/kg) and withdrawal times (24 hours, 68 hours, and 14 days) on 5-HT2C (formerly 5-HT1C) receptors in the rat brain choroid plexus were studied with quantitative receptor autoradiography in two separate experiments. Chronic citalopram treatment caused a consistent and dose-related increase in the density of 5-HT2C receptors (up to 90%). This effect was slightly more pronounced when measured with an antagonist ligand ([3H]mesulergine) than with an agonist ligand [(+/-)-1-(2,5-dimethoxy-4-[125I]iodophenyl)-2-aminopropane ([125I]DOI)]. The upregulation was most evident 24 hours after the last dose and disappeared thereafter rather rapidly. Chronic fluoxetine treatment also increased the density of 5-HT2C receptors 24 hours from the last dose, but the increase was accompanied by a reduced affinity and was less marked than that observed with citalopram. The changes in receptor characteristics were not observed consistently after the 68-hour withdrawal from fluoxetine. Furthermore, the upregulation of fluoxetine appeared not to be dose related or reflected by an increase in agonist binding. In conclusion, the results show that chronic citalopram and fluoxetine treatments induce an increase of choroid plexus 5-HT2C receptor density, but the effect is more marked with citalopram. These differences in the regulation of the 5-HT2C receptors may lead to pharmacodynamic differences between chronic citalopram and fluoxetine treatments.

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Effect of citalopram on the desensitization of serotonin-2A receptor-mediated calcium mobilization in rat glioma cells.

Kagaya A, Kugaya A, Hayashi T, Okamoto Y, Takebayashi M, Uchitomi Y, Yamawaki S.

Department of Psychiatry and Neurosciences, Hiroshima University School of Medicine, Minamiku, Hiroshima, Japan.

1. The authors have investigated the effect of citalopram, an effective antidepressant drug with selective serotonin (5-HT) uptake inhibition, on 5-HT-2A receptor-mediated intracellular calcium (Ca2+) rise in C6 cultured cells. 2. Citalopram, at concentrations of 10 and 30 mu M, did not significantly reduce the Ca2+ mobilization induced by 10 mu M 5-HT, indicating that citalopram has little affinity for 5-HT-2A receptors. 3. Citalopram did not alter a subsequent response to 5-HT after citalopram was pre-applied to the cells. 4. However, citalopram inhibited the desensitization of 5-HT-2A receptors. When the cells were pretreated with citalopram and 5-HT, the subsequent response to 5-HT was significantly greater than that obtained following pretreatment with 5-HT alone. 5. To investigate the mechanism of action of citalopram on the desensitization of 5-HT-2A receptors, NaF-induced cGMP generation was measured. Citalopram inhibited the generation of cGMP induced by NaF in C6 cells as well as W-7. 6. These results indicate that citalopram antagonized the desensitization of 5-HT-2A receptor-mediated Ca2+ mobilization and this antagonism may be mediated by a calmodulin-dependent pathway in C6 glioma cells.

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citalopram escitalopram Lexapro
Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c receptor.

Palvimaki EP, Roth BL, Majasuo H, Laakso A, Kuoppamaki M, Syvalahti E, Hietala J.

Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland.

Interactions of the selective serotonin reuptake inhibitors (SSRIs) citalopram, fluoxetine and its main metabolite norfluoxetine, and the tricyclic antidepressant (TCA) imipramine with the rat serotonin 5-HT2C receptor in a clonal cell line and in the rat choroid plexus were investigated by radioligand binding and phosphoinositide (PI) hydrolysis assays. For comparison, the affinities of a variety of other antidepressants of different chemical classes for the cloned rat 5-HT2C and 5-HT2A receptors were also determined by radioligand binding assays. Fluoxetine displayed relatively high affinity for the 5-HT2C receptor in the choroid plexus, with a Ki value for inhibition of [3H]mesulergine binding of 55.4 nM. The Ki values for imipramine, norfluoxetine and citalopram were 136 nM, 203 nM, and 298 nM, respectively. Similar rank order of potency was detected in PI hydrolysis assays, which showed that these drugs are antagonists at the 5-HT2C receptor without exhibiting inverse agonist activity. [3H]Ketanserin (5-HT2A) binding assays revealed that the SSRIs fluoxetine, norfluoxetine and citalopram show 10- to 23-fold selectivity for the 5-HT2C receptor in vitro, whereas the TCA imipramine does not. Many other TCAs also had high to intermediate affinity for both 5-HT2A and 5-HT2C receptors. The present data provide evidence that fluoxetine, norfluoxetine and citalopram, along with many other antidepressant compounds, interact directly with the 5-HT2C receptor.

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citalopram escitalopram Lexapro
Serotonergic modulation of striatal D2 dopamine receptor binding in humans measured with positron emission tomography.

Tiihonen J, Kuoppamaki M, Nagren K, Bergman J, Eronen E, Syvalahti E, Hietala J.

Department of Forensic Psychiatry, University of Kuopio, Niuvanniemi Hospital, Finland.

The modulating effect of serotonergic drugs on the striatal dopamine neurotransmission has remained controversial, and there are no published data on serotonin-dopamine interaction obtained from living human brain. Citalopram is a selective serotonin reuptake inhibitor widely used in the treatment of depression (20-40 mg/day). We measured the effects of acute (20 mg, per os) and chronic (20 mg/day for 14 days) doses of citalopram and placebo intake on [11C]-raclopride binding to striatal D2-receptors in eight healthy volunteers by using positron emission tomography. Although the effect magnitude was not large, the results indicate that chronic citalopram intake slightly decreases the raclopride binding which may reflect increased dopamine release in the striatum. In addition, after 14 days there was a high correlation between the citalopam plasma levels and the decrease in the [11C]-raclopride binding in both the caudate and the putamen, although statistically significant effect in the raclopride binding potential was more pronounced in the putamen. This report suggests functional interaction of brain dopaminergic and serotonergic systems in vivo in man.

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citalopram escitalopram Lexapro
Citalopram: differential sleep/wake and EEG power spectrum effects after single dose and chronic administration.

Neckelmann D, Bjorvatn B, Bjorkum AA, Ursin R.

Department of Physiology, University of Bergen, Norway. dag.neckelmann phs.ulaval.ca

The sleep/wake effects of the selective serotonin re-uptake inhibitor citalopram were studied in both a single-dose study with three dose levels (0.5, 2.0 and 5.0 mg/kg), and a 5-week chronic administration study (15 mg/kg/24 h). Single doses of citalopram resulted in a dose-dependent inhibition of rapid eye movement (REM) sleep. After chronic citalopram treatment there was a sustained REM sleep inhibition. Single doses of citalopram resulted in only minor changes in non-REM (NREM) sleep as well as in NREM EEG power spectral density. Chronic administration resulted in a major shift from SWS-2 to SWS-1. The observed corresponding changes in EEG power density were regional. A 30 to 40 percent reduction of power density in the 0.5-15 Hz range in the fronto-parietal EEG derivation was seen for the whole 8-h registration period. In the fronto-frontal EEG derivation only minor changes were seen. A decreasing trend in NREM sleep power density between 0.5 and 7 Hz, usually seen during the course of the light period, was not observed in the chronic condition, but was seen in control and single-dose condition, suggesting altered diurnal distribution of slow wave activity in the chronic condition. The data indicate that acute and chronic administration of citalopram shows clear differences in sleep effect, which may be caused by alteration of serotonergic transmission, and may be related to the antidepressant effect.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8883829&dopt=Abstract citalopram escitalopram Lexapro