citalopram escitalopram Lexapro
Paradoxical effects of opioid antagonist naloxone on SSRI-induced analgesia and tolerance in mice.

Singh VP, Patil CS, Jain NK, Singh A, Kulkarni SK.

Research and Development Division, Panacea Biotec Ltd., Punjab, India.

Selective serotonin reuptake inhibitors (SSRIs) have been used clinically as co-analgesics in various devastating painful conditions. Upon chronic treatment tolerance develops to their analgesic effect, which is often refractory to increasing dose. Although modulation of serotonergic pathways considerably explains their clinical efficacy, numerous reports nevertheless indicate the direct/indirect role of the opioidergic pathway in SSRI-induced analgesia. The present study was designed to investigate the effect, if any, of the opioid antagonist naloxone on SSRIs-induced analgesia and tolerance employing acetic acid-induced writhing assay. Two SSRIs, fluoxetine (FLX), and citalopram (CTP) were used in the study. Acute systemic (5-40 mg kg(-1) i.p.), or intrathecal (5-40 microg per mouse, i.t.) administration of fluoxetine or citalopram exhibited a dose-dependent and significant (p < 0.05) antinociceptive effect. Single systemic (2-5 mg kg(-1) i.p.) or intrathecal (1 microg per mouse, i.t.) administration of opioid antagonist naloxone blocked where as systemic ultra-low dose (10 ng/kg) or intrathecal (0.05 ng) naloxone potentiated the acute antinociceptive effect of both SSRIs (10 mg kg(-1) i.p. and 10 microg i.t.). Animals treated chronically over a 7-day period with SSRIs developed tolerance to their antinociceptive effect. Further, chronic administration of ultra-low dose of naloxone intrathecal (0.05 ng per mouse, i.t.) or systemic (10 ng kg(-1) i.p.) with fluoxetine or citalopram (10 microg i.t.; 5 mg kg(-1) i.p.) over a 7-day period reversed the tolerance to the antinociceptive effect of SSRIs. Thus, in ultra-low doses, naloxone paradoxically enhances SSRIs-induced analgesia and reverse tolerance through spinal and peripheral action. These effects of opioid antagonist naloxone on SSRIs-induced antinociception may have an implication in refractory cases upon chronic use of SSRIs as co-analgesics. Copyright 2003 S. Karger AG, Basel

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14512696&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Effects of acute treatment with paroxetine, citalopram and venlafaxine in vivo on noradrenaline and serotonin outflow: a microdialysis study in Swiss mice.

David DJ, Bourin M, Jego G, Przybylski C, Jolliet P, Gardier AM.

EA 3544, Lab. Neuropharmacologie, Faculte de Pharmacie, Universite Paris-Sud, Chatenay-Malabry 92296, France.

1. This study investigated whether a single administration of a range of doses (1, 4 and 8 mg kg-1, i.p.) of paroxetine, citalopram or venlafaxine may simultaneously increase extracellular levels of 5-HT ([5-HT]ext) and noradrenaline ([NA]ext) by using in vivo microdialysis in the frontal cortex (FCx) of awake, freely moving Swiss mice. 2. In vivo, paroxetine induced similar increases in cortical [5-HT]ext at the three doses tested, and induced a statistically significant increase in cortical [NA]ext at 4 and 8 mg x kg-1. Citalopram increased neither [5-HT]ext nor [NA]ext at the lowest dose, but increased both neurotransmitter levels at 4 and 8 mg x kg-1. At these doses, citalopram induced greater increases in cortical [5-HT]ext than in [NA]ext. Venlafaxine increased [5-HT]ext and [NA]ext to about 400 and 140% of the respective basal values at 8 mg kg-1. 3. Citalopram and paroxetine have the highest potency to increase cortical [5-HT]ext and [NA]ext, respectively. In addition, the rank of order of efficacy of these antidepressant drugs to increase [5-HT]ext in vivo in the FCx of mice was as follows: venlafaxine>citalopram>paroxetine, while the efficacy to increase cortical [NA]ext in mice of paroxetine and citalopram is similar, and greater than that of venlafaxine. 4. In conclusion, extracellular levels of cortical [NA]ext increase with the highest doses of the very selective SSRI citalopram, as well as with the very potent SSRI paroxetine. Surprisingly, the SNRI venlafaxine increased cortical [5-HT]ext to a greater extent rather than [NA]ext in the range of doses studied in mice.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14530210&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Overview of the safety of citalopram.

Nemeroff CB.

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, USA. LXK18 psu.edu

Citalopram is a highly selective serotonin reuptake inhibitor (SSRI) that has been prescribed to >30 million patients in >70 countries. The purpose of this focused overview is to summarize the data from well-controlled clinical trials and published literature relative to the safety of citalopram in patients with depression and depressive symptoms. This overview is based mainly on 3 sources: (1) data from clinical trials sponsored by Forest Laboratories, (2) published clinical studies, and (3) case reports. Both pharmacokinetic and pharmacodynamic interactions were scrutinized, as were data on special populations and safety concerns. The available data suggest that citalopram 20-60 mg once daily is safe for patients with depression. Few drugs appear to interact with citalopram in a clinically meaningful way. Well-designed short- and long-term trials demonstrate an overall safety/side effect profile consistent with other SSRIs. The more frequent adverse events (nausea, somnolence, dry mouth, increased sweating) are mainly transient, mostly mild to moderate in severity, and observed consistently across studies at rates similar to other SSRIs. Analysis of laboratory values, ECG, and vital signs revealed no unusual findings. Only a small, clinically unimportant reduction in heart rate was observed, similar to that seen with other SSRIs. Citalopram treatment did not increase risk of suicide, overdose, seizure, or arrhythmia. Thus, the pharmacodynamic, pharmacokinetic, and safety profiles of citalopram demonstrate that it is safe for use in adults with depression and depressive symptoms, including the elderly and patients with mild to moderate renal and hepatic disease.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14561952&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Anxiolytic-like effects of escitalopram, citalopram, and R-citalopram in maternally separated mouse pups.

Fish EW, Faccidomo S, Gupta S, Miczek KA.

Department of Psychology, Tufts University, Medford, Massachusetts 02155, USA.

The S-enantiomer of citalopram, escitalopram, is a selective serotonin reuptake inhibitor (SSRI) that appears to be responsible for citalopram's antidepressant and anxiolytic effects. Clinically, escitalopram is reported to have fewer adverse side effects than do other SSRIs. This study compared escitalopram to other antidepressants in a preclinical procedure predicting anxiolytic-like effects of drugs. Carworth Farms Webster (CFW) mouse pups (7 days old) were separated from the dam and maintained at a temperature of 34 degrees C. Forty-five minutes after administering citalopram (0.56-10 mg/kg), escitalopram (0.0056-3 mg/kg), R-citalopram (1-10 mg/kg), paroxetine (0.3-3 mg/kg), fluoxetine (1-30 mg/kg), or venlafaxine (3-56 mg/kg) subcutaneously, the pups were placed individually on a 19.5 degrees C surface for 4 min. Ultrasonic vocalizations (USVs) (30-80 kHz), grid crossing, rolling (i.e., the pup turned on one side or its back), and colonic temperature were recorded. All the drugs reduced USV emission; escitalopram was the most potent (ED(50) 0.05 mg/kg), followed by paroxetine (0.17 mg/kg), citalopram (1.2 mg/kg), fluoxetine (4.3 mg/kg), R-citalopram (6 mg/kg), and venlafaxine (7 mg/kg). The doses that decreased USVs differed from those that increased motor activity. Increased grid crossing occurred after low doses of paroxetine (0.03 or 0.1 mg/kg) and fluoxetine (1 mg/kg), but only after the highest doses of the citalopram enantiomers and venlafaxine (0.3, 10, and 56 mg/kg, respectively). Except for escitalopram and venlafaxine, high doses of the treatments increased rolling. R-Citalopram caused a 10-fold rightward shift in escitalopram's dose-effect curve, suggesting that R-citalopram inhibits escitalopram's anxiolytic-like effects. These data support clinical findings that escitalopram is a potent, well tolerated SSRI with anxiolytic-like effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14593091&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Potentiation of 5-hydroxytryptamine (5-HT) responses by a 5-HT uptake inhibitor in pulmonary and systemic vessels: effects of exposing rats to hypoxia.

Wanstall JC, Fiore SA, Gambino A, Chess-Williams R.

School of Biomedical Sciences, Department of Physiology and Pharmacology, The University of Queensland, St Lucia, 4072 Brisbane, Queensland, Australia.

The aim was to determine whether uptake of 5-hydroxytryptamine (5-HT) by the 5-HT transporter (SERT) modulates contractile responses to 5-HT in rat pulmonary arteries and whether this modulation is altered by exposure of rats to chronic hypoxia (10% oxygen; 8 h/day; 5 days). The effects of the SERT inhibitor, citalopram (100 nM), on contractions to 5-HT were determined in isolated ring preparations of pulmonary artery (intralobar and main) and compared with data obtained in systemic arteries. In intralobar pulmonary arteries citalopram produced a potentiation (viz. an increase in potency, pEC(50)) of 5-HT. The potentiation was endothelium-dependent in preparations from normoxic rats but endothelium-independent in preparations from hypoxic rats. In main pulmonary artery endothelium-independent potentiation was seen in preparations from hypoxic rats but no potentiation occurred in preparations from normoxic rats. In systemic arteries, citalopram caused endothelium-independent potentiation in aorta but no potentiation in mesenteric arteries; there were no differences between hypoxic and normoxic rats. It is concluded that SERT can influence the concentration of 5-HT in the vicinity of the vasoconstrictor receptors in pulmonary arteries. The data suggest that in pulmonary arteries from hypoxic rats, unlike normoxic rats, the SERT responsible for this effect is not in the endothelium and, hence, is probably in the smooth muscle. The data are compatible with reports that, in the pulmonary circulation, hypoxia induces/up-regulates SERT, and hence increases 5-HT uptake, in vascular smooth muscle. The findings may have implications in relation to the suggested use of SERT inhibitors in the treatment of pulmonary hypertension.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14605793&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Economic evaluation of citalopram use and expenditures among recipients in the Texas Medicaid program.

Johnsrud MT, Crismon ML.

Center for Pharmacoeconomic Studies, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA.

OBJECTIVE: To describe the trends in the utilization and expenditures of selective serotonin reuptake inhibitors (SSRIs) and venlafaxine within the Texas Medicaid program in 1999 and 2000; more specifically, to compare the use of citalopram with other SSRI agents and venlafaxine. METHODS: A retrospective analysis of Texas Medicaid paid prescription claims data involving Texas Medicaid clients aged 18 to 64. The main outcome measures were allowed, discounted cost per day; dose per day; treatment days (persistence); adherence rates; and switching rates. RESULTS: Citalopram had a significantly lower calculated cost per day than all other comparator agents. There were no statistically significant differences between study agent groups when comparing treatment days and adherence days for newly started patients, except for lower rates with venlafaxine IR. CONCLUSIONS: Within the Texas Medicaid Program, citalopram had a positive economic impact on prescription drug costs compared to other comparator agents, while showing similar outcomes in utilization measures such as treatment days and adherence rates.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14613382&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Impaired spatial learning in the Morris water maze induced by serotonin reuptake inhibitors in rats.

Majlessi N, Naghdi N.

Department of Physiology and Pharmacology, Pasteur Institute of Iran, Pasteur Ave., Tehran 13164, Iran. nahidm institute.pasteur.ac.ir

The effects of selective serotonin reuptake inhibitors citalopram and fluoxetine on spatial learning were assessed in rats. Adult male rats were subjected to 4 days of training in the Morris water maze with the invisible platform. Animals received different doses of citalopram (1-8 mg/kg; i.p.) or fluoxetine (1-16 mg/kg; i.p.) or their vehicles (saline or distilled water respectively) 30 minutes before training each day. The results showed that citalopram at doses of 4 and 8 mg/kg and fluoxetine at doses of 8 and 16 mg/kg significantly increased latencies to find the platform and traveled distances compared to the control group. Therefore, it appears that selective serotonin reuptake inhibitors can cause learning deficits in complex spatial tasks such as Morris water maze. Copyright 2002 Lippincott Williams & Wilkins.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12122314&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Regional pattern of binding and c-Fos induction by (R)- and (S)-citalopram in rat brain.

Thomsen C, Helboe L.

Cabral-da-SilvaMolecular Pharmacology, H Lundbeck A/S, Biological Research, Valby, Denmark. ctho lundbeck.com

Citalopram is a racemic mixture of two stereoisomers, (R)- and (S)-citalopram. Both enantiomers were radiolabelled and used for in vitro receptor autoradiography in rat brain. High levels of specific [3H](S)-citalopram binding were observed in the amygdala complex, substantia nigra, superior colliculus and central grey. No specific binding of [3H](R)-citalopram was observed in any brain regions examined. S-citalopram induced a significant increase in c-Fos positive cells in central amygdala and in the bed nucleus of the stria terminalis (BST), compared to vehicle controls. A similar pattern of c-Fos activation was observed with (RS)-citalopram, sertraline and paroxetine, while (R)-citalopram did not increase c-Fos expression in these areas. The high affinity binding and apparent neuronal activation by (RS)-citalopram is thus confined to the (S)-enantiomer.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14663201&dopt=Abstract citalopram escitalopram Lexapro