citalopram Celexa
Worsening of Parkinson's disease by citalopram.

Linazasoro G.

Centro de Neurologia y Neurocirugia funcional, Clinica Quiron, Parque Alcolea, 7 20012, San Sebastian, Spain

More than 50% of the patients with Parkinson's disease (PD) may experience mood disturbances. Serotonin-selective reuptake inhibitors (SSRI) are very active in the management of depression. Citalopram is a new SSRI increasingly used in the treatment of depression. The question of a negative impact of SSRI on the motor function of patients with PD is an important clinical issue. A number of such observations have published with various SSRI, but none, up-to-now with citalopram. We report the case of a patient with PD who experienced a worsening in the motor status soon after the addition of citalopram to her antiparkinsonian drug regime. This single case report suggests that this potential adverse event is a class related side effect.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10699393&dopt=Abstract citalopram Celexa



citalopram Celexa
Increased adenylyl cyclase type 1 mRNA, but not adenylyl cyclase type 2 in the rat hippocampus following antidepressant treatment.

Jensen JB, Mikkelsen JD, Mork A.

Department of Clinical Biochemistry, Bispebjerg Hospital, Bispebjerg Bakke 23, DK-2400, Copenhagen, Denmark. jej lundbeck.com

The adenylyl cyclase (AC) system is affected by several types of antidepressant treatments, and increased activity in this system is linked to the therapeutic action of antidepressants. The present study was undertaken to compare the effects of single-dose and long-term treatment with the selective serotonin reuptake inhibitor, citalopram (10 mg/kg, i.p.), on the AC system in the male rat brain of Wistar rats. Furthermore, we compared the effects of long-term citalopram and lithium treatments on the AC system. Long-term citalopram, but not single-dose administration, increased the AC type 1 mRNA in the hippocampus, whereas type 2 mRNA was unaffected. Long-term lithium treatment also increased AC1 in the hippocampus. However, long-term citalopram treatment did not increase AC type 1 protein, basal or forskolin-stimulated AC activity, but GTP increased AC activity in the hippocampus. This may indicate enhanced AC/G protein coupling. Thus, citalopram may increase cAMP signalling by acting on components of the AC system without affecting the protein level of the AC type 1.

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citalopram Celexa
Citalopram reduces social interaction in rats by activation of serotonin (5-HT)(2C) receptors.

Dekeyne A, Denorme B, Monneyron S, Millan MJ.

Institut de Recherches Servier, Psychopharmacology Department, 125, Chemin de Ronde, 78290 Croissy-sur-Seine, Paris, France.

The selective serotonin (5-HT) reuptake inhibitor (SSRI), citalopram (2.5 mg/kg, s.c.), reduced social interaction (SI) in rats. This action was abolished by the 5-HT(2B/2C) receptor antagonist, SB206, 553 (0.63 mg/kg, s.c.), and the 5-HT(2C) receptor antagonist, SB242, 084 (0.04 mg/kg, i.p.), but not by the 5-HT(2A) antagonist, MDL100, 907 (0.04 mg/kg, s.c.), the 5-HT(1A) antagonist, WAY100,635 (0.16 mg/kg, s.c.), or the 5-HT(3) antagonist, ondansetron (0.16 mg/kg, s. c.). These data suggest that 5-HT(2C) receptors are involved in the "anxiogenic" actions of citalopram.

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citalopram Celexa
The use of citalopram in an integrated approach to the treatment of eating disorders: an open study.

Calandra C, Gulino V, Inserra L, Giuffrida A.

Service for the Therapy of Eating Disorders, University Hospital of Catania, Italy.

This study investigated the efficacy and safety of citalopram in the treatment of eating disorders. Eighteen female patients gave their informed consent to enrollment in the trial: twelve with bulimia nervosa, six with anorexia nervosa according to the DSM IV criteria. They received individual systemic psychotherapy and took 20 mg/day citalopram for 8 weeks. At the beginning and end of the trial, their BMI, body fat and lean mass were checked and they completed the Eating Disorder Inventory and Binge Scale. The results showed that citalopram is effective and safe in the treatment of eating disorders: binge eating episodes and mean scores in three EDI subscales (bulimia, ineffectiveness and interoceptive awareness) significantly decreased in the bulimic patients, and mean scores in the EDI body dissatisfaction subscale significantly decreased in the anorexic patients.

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citalopram Celexa
The effect of citalopram treatment on platelet serotonin function in panic disorders.

Neuger J, Wistedt B, Sinner B, Aberg-Wistedt A, Stain-Malmgren R.

Karolinska Institute, Institution of Clinical Neuroscience, Department of Psychiatry, St Goran's Hospital, Stockholm, Sweden. Jolanta.Neuger cspo.sll.se

We investigated the effect of the selective serotonin reuptake inhibitor (SSRI) citalopram after 6-8 weeks and 6 months of treatment on clinical and peripheral indexes for central serotonergic function: platelet [14C]serotonin uptake and [3H]paroxetine- and [3H]LSD-binding to platelets membranes in 33 patients with panic disorder. Basal data from patients were compared with data from a control material consisting of 33 healthy volunteers. Bmax for platelet [3H]paroxetine binding was significantly lower in patients than in controls. There were no differences in serotonin uptake or [3H]LSD-binding between patients and controls. The degree of anxiety and depression was assessed using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory self-assessment scales, and the Clinical Anxiety Scale and the Montgomery Asberg Depression Rating Scale for clinical evaluation. Complete remission was found in one third of the patients after 6-8 weeks and in two-thirds after 6 months of treatment. The reduction in assessment scores was parallelled with similar reductions in platelet 5-HT2-receptor density, [3H]LSD affinity variable (Kd) and Vmax for platelet [14C]5-HT uptake. Citalopram treatment did not alter Bmax and Kd for platelet [3H]paroxetine-binding. A positive correlation was found between Vmax for the platelet [14C]5-HT uptake and BAI after 6 months citalopram treatment. The present study shows that citalopram has a therapeutic effect in panic disorders. A prerequisite of responding to treatment might be plasticity in the serotonergic system.

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citalopram Celexa
Mirtazapine enhances frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission by blockade of alpha2-adrenergic and serotonin2C receptors: a comparison with citalopram.

Millan MJ, Gobert A, Rivet JM, Adhumeau-Auclair A, Cussac D, Newman-Tancredi A, Dekeyne A, Nicolas JP, Lejeune F.

Psychopharmacology Department, Institut de Recherches Servier, Centre de Recherches de Croissy, 125, Chemin de Ronde, 78290, Croissy-sur-Seine, Paris, France.

Mirtazapine displayed marked affinity for cloned, human alpha2A-adrenergic (AR) receptors at which it blocked noradrenaline (NA)-induced stimulation of guanosine-5'-O-(3-[35S]thio)-triphosphate ([35S]-GTPgammaS) binding. Similarly, mirtazapine showed high affinity for cloned, human serotonin (5-HT)2C receptors at which it abolished 5-HT-induced phosphoinositide generation. Alpha2-AR antagonist properties were revealed in vivo by blockade of UK-14,304-induced antinociception, while antagonist actions at 5-HT2C receptors were demonstrated by blockade of Ro 60 0175-induced penile erections and discriminative stimulus properties. Mirtazapine showed negligible affinity for 5-HT reuptake sites, in contrast to the selective 5-HT reuptake inhibitor, citalopram. In freely moving rats, in the dorsal hippocampus, frontal cortex (FCX), nucleus accumbens and striatum, citalopram increased dialysate levels of 5-HT, but not dopamine (DA) and NA. On the contrary, mirtazapine markedly elevated dialysate levels of NA and, in FCX, DA, whereas 5-HT was not affected. Citalopram inhibited the firing rate of serotonergic neurons in dorsal raphe nucleus, but not of dopaminergic neurons in the ventral tegmental area, nor adrenergic neurons in the locus coeruleus. Mirtazapine, in contrast, enhanced the firing rate of dopaminergic and adrenergic, but not serotonergic, neurons. Following 2 weeks administration, the facilitatory influence of mirtazapine upon dialysate levels of DA and NA versus 5-HT in FCX was maintained, and the influence of citalopram upon FCX levels of 5-HT versus DA and NA was also unchanged. Moreover, citalopram still inhibited, and mirtazapine still failed to influence, dorsal raphe serotonergic neurons. In conclusion, in contrast to citalopram, mirtazapine reinforces frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission. These actions reflect antagonist properties at alpha2A-AR and 5-HT2C receptors.

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citalopram Celexa
Adaptive changes in the reactivity of 5-HT1A and 5-HT2 receptors induced in rat frontal cortex by repeated imipramine and citalopram.

Bobula B, Tokarski K, Zahorodna A, Hess G.

Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland.

Using extracellular ex vivo recording we studied changes in the reactivity of rat frontal cortical neurons to the 5-HT(1A), 5-HT(2) and 5-HT(4) receptor agonists (+/-)-2-dipropyloamino-8-hydroxy-1,2,3,4-tetrahydronaphtalene hydrobromide (8-OH-DPAT), (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) and zacopride, respectively, induced by a repeated treatment with imipramine or citalopram. Rats were treated with imipramine or citalopram for 14 days (10 mg/kg p.o.) twice daily. Frontal cortical slices were prepared 2 days after the last drug administration. Spontaneous epileptiform discharges were induced in slices by perfusion with a medium devoid of Mg(2+) ions and with added picrotoxin (30 microM). While the application of 2 microM 8-OH-DPAT resulted in a reversible decrease of the discharge frequency, in the presence of DOI (1 microM) or zacopride (5 microM), the discharge frequency was increased. Both repeated imipramine and citalopram enhanced the effect of the activation of 5-HT(1A) receptor and attenuated the effect related to 5-HT(2) receptor activation, while the effect of the activation of 5-HT(4) receptor remained unchanged. Moreover, imipramine, but not citalopram, induced a reduction of epileptiform discharge frequency and an increase of the time of occurrence of epileptiform activity. These data indicate that antidepressants enhance the 5-HT-mediated inhibition in neuronal circuitry of the frontal cortex.

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citalopram Celexa
Effect of acute treatment with YM992 on extracellular serotonin levels in the rat frontal cortex.

Hatanaka K, Yatsugi S, Yamaguchi T.

Neuroscience Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Japan. hatanaka yamanouchi.co.jp

(S)-2-[[(7-fluoroindan-4-yl)oxy]methyl]morpholine monohydrochloride (YM992) is a novel putative antidepressant exhibiting both selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibition and 5-HT(2A) receptor antagonism. In vivo microdialysis revealed that a single treatment with YM992 (3, 10, 30 mg/kg i.p.) dose-dependently increased extracellular 5-HT levels in the rat frontal cortex. Fluoxetine, citalopram and venlafaxine also produced significant increases in 5-HT levels at doses of 10-30 mg/kg. However, the increase in 5-HT levels induced by YM992 was significantly larger than increases elicited by these three compounds at 30 mg/kg. The combined administration of R-(+)-alpha-(2, 3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidine-methanol (MDL100,907) (a selective 5-HT(2A) receptor antagonist) and citalopram produced no additional increase in 5-HT levels compared with citalopram treatment alone. YM992 moderately enhanced [3H]5-HT release from rat cerebral cortex synaptosomes using different mechanisms than p-chloroamphetamine. In comparison, 10-microM fluoxetine markedly induced 5-HT release in vitro, while citalopram and venlafaxine had no noticeable effect on release. YM992 produces a more robust increase of 5-HT levels acutely than other antidepressants in vivo and the effect may be due to 5-HT releasing properties of the drug.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10781669&dopt=Abstract citalopram Celexa