citalopram escitalopram Lexapro
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 escitalopram Lexapro
[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 escitalopram Lexapro
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 escitalopram Lexapro
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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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 escitalopram Lexapro
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.

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citalopram escitalopram Lexapro
The involvement of dopamine (DA) and serotonin (5-HT) in stress-induced stereotypies in bank voles (Clethrionomys glareolus).

Schoenecker B, Heller KE.

Zoological Institute, University of Copenhagen, Tagensvej 16, DK-2200 N, Copenhagen, Denmark

In order to clarify the dependency of stress-induced stereotypies on dopamine (DA) and serotonin (5-HT) functioning, undisturbed and acutely stressed stereotyping bank voles were treated during 3 weeks with the commonly used human atypical neurolepticum clozapine and the SSRI antidepressant citalopram. Clozapine blocks DA receptors (D sub (4)) and acts as a partial 5-HT antagonist (5-HT sub (2) receptors), while citalopram increases 5-HT transmitter activity. Levels of stereotypies were quantified under undisturbed conditions during the treatment period and immediately after the acute stress of handling and injections. It was demonstrated that stereotypies are markedly increased after acute stress and that citalopram effectively mitigates this stress effect. Stereotypies under undisturbed conditions were left unaffected by both clozapine and citalopram treatments.It is suggested that stress-induced increases in stereotypies are more dependent on 5-HT than DA functioning.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11434965&dopt=Abstract citalopram escitalopram Lexapro