citalopram Celexa
Effect of acute and chronic administration of citalopram on glutamate and aspartate release in the rat prefrontal cortex.

Golembiowska K, Dziubina A.

Department of Pharmacology, Institute of Pharacology, Polish Academy of Sciences, Krakow. nfgolemb cyf-kr.edu.pl

The present study was designed to determine whether peripheral administration of the selective serotonin reuptake inhibitor (SSRI) citalopram influenced glutamate and aspartate release in the rat prefrontal cortex using in vivo microdialysis. Citalopram was given acutely at doses of 10 and 20 mg/kg or chronically at a dose of 10 mg/kg daily for two weeks, in both cases by intraperitoneal (ip) route. Citalopram given at a single dose of 20 mg/kg, but not 10 mg/kg, significantly inhibited release of glutamate and aspartate induced by sodium channel activator, veratridine (100 microM). Glutamate and aspartate release was also diminished in animals treated chronically with citalopram. Citalopram did not affect extracellular level of 5-hydroxytryptamine (5-HT) after acute doses, but increased it after chronic administration. On the other hand, single and repeated doses of the drug inhibited veratridine-evoked 5-HT release. Neither single nor chronic treatment with citalopram influenced spontaneous and evoked dopamine (DA) release. The results suggest that in the presence of depolarizing agent, e.g. under conditions resembling a disturbed homeostasis of neuronal network, antidepressant drugs with profile of SSRI may influence excitatory systems in the brain. This effect does not seem to be dependent on the interaction with 5-HT or DA neurotransmission, but rather some inhibitory modulators stimulated in stress situations may contribute to the observed results.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11334237&dopt=Abstract citalopram Celexa



citalopram Celexa
Progressive attenuation of the firing activity of locus coeruleus noradrenergic neurons by sustained administration of selective serotonin reuptake inhibitors.

Szabo ST, de Montigny C, Blier P.

Sustained administration of the selective serotonin (5-HT) reuptake inhibitors (SSRIs) citalopram for 2, 14, and 21 d, and paroxetine for 2 and 21 d (20 and 10 mg/kg.d, respectively, s.c. using osmotic minipumps) produced a gradual decrease in spontaneous firing activity of locus coeruleus (LC) noradrenergic neurons. In contrast, sustained desipramine administration for 2 and 21 d (10 mg/kg.d) robustly reduced LC firing activity, though only to the same extent, following these two treatment periods. The enhancement of the firing rate of LC neurons produced by the 5-HT1A agonist 8-OH-DPAT (10-50 &mgr;g/kg, i.v.) in desipramine- and citalopram-treated rats was abolished, indicating a desensitization of 5-HT1A receptors. However, the attenuation of the firing rate of LC neurons induced by the 5-HT2 agonist DOI (5-50 &mgr;g/kg, i.v.) was decreased approx. 2-fold in citalopram-treated rats but not significantly altered in desipramine-treated rats. Since 5-HT neurons exert a tonic inhibitory effect on LC neurons, it appears that enhancing 5-HT neurotransmission by sustained SSRI administration leads to a reduction of the firing rate of noradrenergic neurons. In conclusion, SSRIs attenuate the activity of noradrenergic neurons with a delay that is consistent with their beneficial effect in depression and some anxiety disorders, such as panic, generalized and social anxiety disorders. However, given the hyperadrenergic state often observed in anxiogenic conditions the latter phenomenon is believed to contribute more to the anxiolytic effect of SSRIs than to their antidepressant action.

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citalopram Celexa
Open trial of citalopram in adults with post-traumatic stress disorder.

Seedat S, Stein DJ, Emsley RA.

The selective serotonin reuptake inhibitors (SSRIs) are rapidly emerging as preferred first-line drugs in the pharmacological management of post-traumatic stress disorder (PTSD). Citalopram, an SSRI with highly potent and selective serotonin reuptake inhibition, may be a useful agent for treating the intrusive, avoidance, and arousal symptoms that characterize PTSD. Fourteen adult subjects (12 with civilian-related post-traumatic stress disorder, and 2 with combat-related post-traumatic stress disorder) were entered into an 8 wk, open- label, fixed-dose trial of citalopram, commencing with 20 mg/d, and increasing to 40 mg/d after 2 wk. Eleven subjects completed 8 wk treatment and were included in the data analysis. Based on the Clinician-Administered Post-traumatic Stress Disorder Scale (CAPS-2), there was significant reduction in all core PTSD symptoms (re-experiencing, hyperarousal, and avoidance) by week 8. Nine of the 11 completers were classified as 'responders' on Clinical Global Impression Improvement scores. Secondary measures of depression (Montgomery-Asberg Depression Rating Scale) and anxiety (Hamilton Anxiety Scale) also improved significantly by week 8. Citalopram was tolerated well, and there were no dropouts due to adverse effects. Data from this preliminary open trial suggests that citalopram, an SSRI, may be effective for reducing the key symptoms of PTSD, however, these findings need confirmation in double-blind, placebo-controlled trials.

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citalopram Celexa
[Behavioral and neurochemical study on the mechanism of the anxiolytic effect of a selective serotonin reuptake inhibitor, a selective serotonin1A agonist and lithium carbonate]

[Article in Japanese]

Muraki I.

Department of Psychiatry, Neural Function, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.

The authors investigated the effects of citalopram [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 the expression of conditioned freezing, an index of anxiety, and on extracellular 5-HT concentrations in the medial prefrontal cortex (mPFC). In conditioned fear stress experiments, acute administration of citalopram (s.c.) reduced freezing significantly at a high dose (30 mg/kg), while showing no effect at lower doses (3 and 10 mg/kg). Acute administration of MKC-242 (s.c.; 0.1-10 mg/kg) dose-dependently reduced freezing. Subchronic lithium treatment (1 week; 0.05 or 0.2% lithium carbonate in diet; p.o.) showed no effect on freezing behavior. Acute treatment with both citalopram (3 and 30 mg/kg) and MKC-242 (1 mg/kg) after subchronic treatment with high, but not low, concentrations of lithium (1 week) reduced freezing markedly and significantly, as compared with either drug alone. In brain microdialysis experiments, acute treatment with citalopram showed significant increases in the extracellular 5-HT concentrations in a dose-dependent manner. Subchronic lithium group showed significantly higher basal levels of extracellular 5-HT, compared with normal diet controls. Acute citalopram (3 and 30 mg/kg) treatment with subchronic lithium treatment showed significant increases in the extracellular 5-HT concentrations, compared with citalopram treatment alone. Subchronic lithium did not cause decreases in extracellular 5-HT after presynaptic stimulation of 5-HT1A receptors by MKC-242. These results suggest that subchronic lithium treatment enhanced the anxiolytic-like effects of these serotonergic drugs by facilitating central 5-HT neurotransmission at clinically therapeutic plasma lithium levels. It is hypothesized that subchronic lithium treatment gives an additive effect to the treatment with citalopram (3 and 30 mg/kg) by increasing the extracellular 5-HT concentrations in the mPFC, and that subchronic lithium treatment enhances the anxiolytic effect of MKC-242 by increasing sensitivity of postsynaptic 5-HT1A receptors.

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citalopram Celexa
Involvement of 5-HT1A and 5-HT1B receptors for citalopram-induced hypothermia in the rat.

Oerther S, Ahlenius S.

Department of Physiology and Pharmacology, Division of Pharmacology, Karolinska Institutet, 17177 Stockholm, Sweden.

OBJECTIVES: To examine the role of 5-HT1A and 5-HT1B receptors for citalopram-induced hypothermia in the rat. METHODS: Core temperature measurements were performed in adult male Wistar rats (305-340 g) using a computer-assisted recording instrument. The temperature readings were automated and gave a printout when the core temperature had stabilised at +/- 0.1 degree C for 10 s. RESULTS: Citalopram (6.25-100.0 mumol/kg) produced a dose-dependent hypothermia. The effect was maximal within 60 min after administration, and had waned off at 120 min. The 5-HT1B receptor agonist anpirtoline (0.25-4.0 mumol/kg) produced a dose-dependent decrease in core temperature. The citalopram-induced hypothermia (25 mumol/kg) was antagonised by pretreatment with either of the 5-HT1A and the 5-HT1B receptor antagonists, WAY-100,635 (0.04 mumol/kg) and NAS-181 (1.0 mumol/kg), respectively, or by the two drugs in combination. Subchronic treatment with the SSRI zimeldine (100 mumol/kg once daily for 2 weeks) resulted in tolerance to the hypothermic effect of citalopram (100 mumol/kg). CONCLUSIONS: The hypothermia produced by acute administration of the SSRI citalopram is mediated via activation of 5-HT1A, as well as 5-HT1B receptors, and this effect is subject to the development of tolerance.

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citalopram Celexa
Binding characteristics of selective serotonin reuptake inhibitors with relation to emission tomography studies.

Elfving B, Bjornholm B, Ebert B, Knudsen GM.

Neurobiology Research Unit N9201, Rigshospitalet, University Hospital Copenhagen, DK-2100 Copenhagen, Denmark. belfving pet.rh.dk

When developing ligands for emission tomography studies, one of the major obstacles lies in the selection of ligand candidates. A previously unattended factor such as the influence of temperature on candidate ligand affinity is likely to play a role. By use of rat brain homogenates, the binding characteristics of [(3)H]-(S)-citalopram and [(3)H]-(+)-McN5652 and the receptor-ligand interaction at the serotonin transporter of 17 selective serotonin reuptake inhibitors were compared at 21 degrees C and 37 degrees C, respectively. Ligand logP values were also calculated. The ratios for K(i) at 37 degrees C vs. 21 degrees C varied between 0.2 and 2.2 for the selective serotonin reuptake inhibitors considered in this study, with most of the ligands displaying an inverse relationship between K(i) and temperature. Ten of the 17 selective serotonin reuptake inhibitors were found to have pK(i) values statistically significantly different at 21 degrees C compared to 37 degrees C (P < 0.05). The logP values ranged between 3.6 and 4.8, except for DASB, 5-iodo-6-nitroquipazine, and paroxetine where logP was 1.9, 2.2, and 5.0, respectively. K(d) was 0.71 nM at 37 degrees C and 0.31 nM at 21 degrees C for [(3)H]-(S)-citalopram. For [(3)H]-(+)-McN5652 K(d) was 0.11 nM at 37 degrees C and 0.08 nM at 21 degrees C. The association and dissociation was much faster for [(3)H]-(S)-citalopram as compared to [(3)H]-(+)-McN5652. It is concluded that temperature may affect K(d) differently and that in vitro dissociation may help to predict whether a given ligand may be useful in PET studies. LogP values do not per se predict the potential of a given ligand as an emission tomography tracer. Copyright 2001 Wiley-Liss, Inc.

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citalopram Celexa
Rapid determination of citalopram in human plasma by high-performance liquid chromatography.

Macek J, Ptacek P, Klima J.

Pharmakl s.r.o., Prague, Czech Republic. pharmakl mbox.vol.cz

A rapid high-performance liquid chromatographic method for the quantitation of citalopram in human plasma is presented. The sample preparation involved liquid-liquid extraction of citalopram with hexane-isoamyl alcohol (98:2 v/v) and back-extraction of the drug to 0.02 M hydrochloric acid. Liquid chromatography was performed on a cyano column (45 x 4.6 mm, 5 microm particles), the mobile phase consisted of an acetonitrile-phosphate buffer, pH 6.0 (50:50, v/v). The run time was 2.6 min. The fluorimetric detector was set at an excitation wavelength of 236 nm and an emission wavelength of 306 nm. Verapamil was used as the internal standard. The limit of quantitation was 0.96 ng/ml using 1 ml of plasma. Within- and between-day precision expressed by relative standard deviation was less than 7% and inaccuracy did not exceed 6%. The assay was applied to the analysis of samples from a pharmacokinetic study.

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citalopram Celexa
Relationship between central serotonergic neurotransmission and reduction in alcohol intake by citalopram.

Berggren U, Eriksson M, Fahlke C, Balldin J.

Department of Psychiatry and Neurochemistry, Institute of Clinical Neuroscience, Goteborg University, Sahlgrenska University Hospital/Molndal, SE-43180, Molndal, Sweden.

The relationship between the effect of citalopram on alcohol intake and central serotonergic neurotransmission, as assessed by prolactin (PRL) response to fenfluramine, was investigated in 17 male heavy drinkers. A positive correlation was obtained, suggesting that the status of central serotonergic neurotransmission in individuals is associated with the treatment response to citalopram. When the group of subjects were divided into those with high and low PRL response (above and below median, respectively) to fenfluramine, those with high PRL response had a significant reduction in alcohol intake during citalopram treatment, whereas those with low PRL response had no such effect. Thus, in subjects with evidence of unimpaired or only slightly impaired central serotonergic neurotransmission (high PRL response) citalopram may have beneficial effect on alcohol consumption, whereas in those with more evidently impaired serotonergic neurotransmission (low PRL response) citalopram treatment may have no effect on or may even increase the alcohol consumption.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11418230&dopt=Abstract citalopram Celexa