citalopram escitalopram Lexapro
Catalepsy induced by the 5-HT(1A) receptor antagonist WAY 100635 in rats pretreated with the selective serotonin reuptake inhibitor citalopram.

Eltayb A, Svensson TH, Ahlenius S.

Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77, Stockholm, Sweden.

Neither a high dose of the selective serotonin reuptake inhibitor citalopram (100 micromol kg(-1) s.c.), nor the 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide 3HCl (WAY 100635) (0.1--0.4 micromol kg(-1) s.c.) produced any evidence of catalepsy in adult male rats. When combined with citalopram, however, WAY 100635 produced a dose-dependent, and statistically significant, catalepsy in the inclined grid test.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11164384&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Effects of MDMA (ecstasy) on prepulse inhibition and habituation of startle in humans after pretreatment with citalopram, haloperidol, or ketanserin.

Liechti ME, Geyer MA, Hell D, Vollenweider FX.

Psychiatric University Hospital Zurich, Zurich, Switzerland.

Prepulse inhibition (PPI) of the acoustic startle response is an operational measure of sensorimotor gating that can be assessed in animals and in humans. Serotonin releasers such as MDMA disrupt PPI and reduce startle habituation in rodents. These effects are prevented by pretreatment with selective serotonin uptake inhibitors, indicating that the effect of MDMA on startle plasticity is largely due to carrier-mediated release of serotonin from presynaptic terminals. In contrast, MDMA has been shown to increase PPI in humans. It is unclear, however, whether the MDMA-induced increase in PPI in humans is also dependent on carrier-mediated serotonin release and which postsynaptic receptors are involved. We investigated the effects of three different pretreatments on the MDMA-induced effects on PPI and habituation in humans. Pretreatments were: (1) the highly selective serotonin uptake inhibitor citalopram (40 mg IV) in 16 subjects, (2) the D(2) antagonist haloperidol (1.4 mg IV) in 14 subjects, and (3) the 5-HT(2A/C) antagonist ketanserin (50 mg PO) in 14 subjects. Each of the three studies used a double-blind placebo-controlled design. All healthy volunteers were examined four times at 2-4-week intervals after placebo, pretreatment, MDMA (1.5 mg/kg PO), and pretreatment plus MDMA. MDMA increased PPI. Habituation was not altered by MDMA, although MDMA-induced individual differences on habituation and psychological symptoms were inversely correlated. Citalopram attenuated the MDMA-induced increase in PPI and most of the psychological effects of MDMA. Neither haloperidol nor ketanserin had any effect on PPI increases produced by MDMA, although each partially attenuated some MDMA-induced psychological effects. Results are consistent with the view that MDMA increases PPI of the acoustic startle reflex in humans via release of presynaptic serotonin.

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citalopram escitalopram Lexapro
An open trial of citalopram in adolescents with post-traumatic stress disorder.

Seedat S, Lockhat R, Kaminer D, Zungu-Dirwayi N, Stein DJ.

Department of Psychiatry, University of Stellenbosch, Tygerberg, Cape Town, South Africa.

In this preliminary, 12-week open-label study, eight adolescents with moderate to severe post-traumatic stress disorder (PTSD) were treated with citalopram (the most selective of the selective serotonin reuptake inhibitors) in a fixed daily dose of 20 mg, and rated at 2-week intervals. The Clinician-Administered PTSD Scale (Child and Adolescent Version) was the primary measure used to assess treatment outcome. Core PTSD symptoms (re-experiencing, avoidance, and hyperarousal symptoms) showed statistically significant improvement at week 12 on the Clinician-Administered PTSD Scale (Child and Adolescent Version) (CAPS-CA), with a 38% reduction in total CAPS scores between baseline and endpoint. Citalopram failed to effect improvement on self-reported depressive symptoms. All seven adolescent completers were rated as much improved or very much improved on Clinical Global Impression Improvement scores. Citalopram was well-tolerated overall with reported adverse experiences being relatively benign. However, larger, controlled trials are needed to consolidate these preliminary results.

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citalopram escitalopram Lexapro
Chronic pharmacological treatment with certain antidepressants alters the expression and DNA-binding activity of transcription factor AP-2.

Damberg M, Ekblom J, Oreland L.

Department of Neuroscience, Section of Pharmacology, Uppsala University, Sweden.

Several of the genes in the serotonergic and the dopaminergic systems have consensus binding sites for the AP-2 transcription factor family in their regulatory regions. Imbalances in these systems have been implicated in many psychiatric disorders, including depression and bipolar affective disorder. We have made an effort to further elucidate the molecular mechanisms of drugs used for affective disorders. Recently, we analyzed the effects of chronic treatment with certain antidepressants on AP-2 in rat brain. The present study demonstrates that chronic administration of three different classes of antidepressants modulates the DNA-binding activity of AP-2 in the rat brain. Chronic administration of citalopram (10 mg/kg), imipramin (10 mg/kg) and lithium-chloride (40 mg/kg) significantly decreased DNA-binding activity of AP-2. Furthermore, citalopram (10 mg/kg) and imipramin (10 mg/kg) significantly decreased the amount of AP-2alpha protein as determined by ELISA. In addition, citalopram (10 mg/kg) significantly decreased the amount of AP-2beta protein. In contrast, chronic administration of lithium-chloride (40 mg/kg) did not affect the amount of the two AP-2 isoforms. An increased understanding of the function of transcription factors and their involvement in human disease, such as depression, could make it possible in the future to selectively modulate relevant target genes directly.

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citalopram escitalopram Lexapro
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.

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citalopram escitalopram Lexapro
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.

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citalopram escitalopram Lexapro
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.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11218145&dopt=Abstract citalopram escitalopram Lexapro