citalopram Celexa
Age-dependent changes in serotonergic modulation of yawning in the rat.

Urba-Holmgren R, Holmgren B, Leon BA, Ugarte A.

Departamento de Ciencias Fisiologicas, Universidad Autonoma de Puebla, Mexico.

Serotonin (5-HT) effects on physostigmine (PHY)-induced yawning were studied in LY Sprague-Dawley rats by injecting Lu 10 171 (citalopram), a specific 5-HT uptake blocker, and two antagonists--methiothepine and ritanserin--which differ slightly in the selectivity of their actions on different 5-HT receptor subtypes. Infant and young rats show significant increases in PHY-induced yawning when preinjected with citalopram (5-10 mg/kg). Two-month-old animals show this effect only with 10 mg/kg. With adult animals (3-5 months old), the effect is the opposite: Yawning decreases. The facilitory effect in infant and young rats was counteracted by methiothepine but not by ritanserin, suggesting that it is mediated through 5-HT1A or 5-HT1B receptor subtypes. The inhibitory effect of citalopram in adult rats was unmodified by the two antagonists used, leaving open the possibility that it is mediated by 5-HT3 receptors.

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citalopram Celexa
Citalopram's ability to increase the extracellular concentrations of serotonin in the dorsal raphe prevents the drug's effect in the frontal cortex.

Invernizzi R, Belli S, Samanin R.

Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.

Administered intraperitoneally to rats at 1 mg/kg, citalopram, a potent and selective inhibitor of serotonin uptake, significantly increased dialysate serotonin in the dorsal raphe, but not in the frontal cortex. At 10 mg/kg citalopram had a greater effect on raphe serotonin and a moderate and short-lasting increase in the dialysate serotonin in the frontal cortex. Citalopram 1 mg/kg i.p. significantly increased the extracellular concentration of serotonin in the frontal cortex of rats which had received a continuous infusion of 1 microM methiothepine in the dorsal raphe, a condition which by itself did not change cortical serotonin concentrations. The results suggest that the ability of serotonin uptake inhibitors to enhance the extracellular concentrations of serotonin in the dorsal raphe attenuates the drug's effect in the frontal cortex.

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citalopram Celexa
The pharmacological effect of citalopram residues in the (S)-(+)-enantiomer.

Hyttel J, Bogeso KP, Perregaard J, Sanchez C.

H. Lundbeck A/S, Research & Development, Copenhagen, Denmark.

The enantiomers of citalopram and N-demethylcitalopram have been investigated. Based on the inhibition of 5-HT uptake in vitro and the potentiation of 1-5-HTP in vivo the pharmacological activity resides in the (+)-enantiomers (the eutomers*) with the 1-(S) absolute configuration. In the 5-HT uptake test eudismic ratios of 167 and 6.6 are obtained for the enantiomers of citalopram and N-demethylcitalopram, respectively. The pharmacological profile of the eutomers of citalopram and N-demethylcitalopram very much resembles the profile of the respective racemates.

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citalopram Celexa
Citalopram: labelling with carbon-11 and evaluation in rat as a potential radioligand for in vivo PET studies of 5-HT re-uptake sites.

Hume SP, Pascali C, Pike VW, Turton DR, Ahier RG, Myers R, Bateman DM, Cremer JE, Manjil LG, Dolan R.

MRC Cyclotron Unit, Hammersmith Hospital, London, England.

In vivo autoradiography of [N-methyl-3H]citalopram in rat brain shows a differential regional localization which correlates with the localization of 5-HT re-uptake binding sites defined in vitro. A comparison of the biodistribution of [N-methyl-3H]citalopram over 2 h after i.v. injection in (1) control rats (2) rats pre-dosed with either citalopram or paroxetine and (3) rats chemically-lesioned with p-chloroamphetamine provides an estimate of specific binding relative to total binding in vivo. The ratio of binding in certain regions (e.g. cingulate) to binding in a reference tissue (e.g. cerebellum) at 30-120 min post injection is c. 1.4. In view of these results a method was developed for labelling citalopram with carbon-11 (t1/2 = 20.3 min, beta + = 99.8%) to provide a potential radioligand for studies using positron emission tomography. Thus, reaction of nca [11C]iodomethane, prepared from cyclotron-produced [11C]carbon dioxide, with norcitalopram in ethanol containing 2,2,6,6-tetramethyl-piperidine for 5 min at 95 degrees C gives crude [N-methyl-11C]citalopram in 60% radiochemical yield, decay-corrected. HPLC on silica gel provides radiochemically and chemically pure [N-methyl-11C]citalopram, as assessed by TLC, HPLC and MS. This product (isolated radiochemical yield, 49%) is easily formulated for i.v. injection. Up to 2 GBq of formulated product with a specific activity of c. 15 GBq/mumol have been prepared within 40 min from the end of radionuclide production. The described radiosynthesis has also been applied to give the single biologically active (+)-enantiomer of [N-methyl-11C]citalopram rather than the racemate. This product gives enhanced specific signal in the rat following i.v. injection, the ratio of uptake in regions of interest relative to cerebellum approaching 2 at 90 min.

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citalopram Celexa
Chronic citalopram action and the maturing mouse brain's indoleamine levels.

Baker PC, Hoff KM.

Department of Biology, Cleveland State University, OH 44115.

1. Mice of various ages between birth and adulthood were injected daily for 12 days with the serotonin specific uptake inhibitor citalopram (LU 10-171). 2. Two hours, 1 day and 3 days following the last injection animals were killed and their brains assayed for 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA). 3. Changes in levels of both metabolites varied by age of the animal, brain region and time after last injection. These patterns differed from previous studies of shorter duration citalopram exposure. 4. The data support the view that 5-HT and 5-HIAA levels are probably not dependently related in immature brain. Indeed 5-HIAA modulation in the immature seems to lack the firm control of the adult and can be modified for extended periods by citalopram action.

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citalopram Celexa
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.

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citalopram Celexa
Effect of repeated treatment with antidepressant drugs and electroconvulsive shock (ECS) on the D2 dopaminergic receptor turnover in the rat brain.

Nowak G, Zak J.

Institute of Pharmacology, Polish Academy of Sciences, Smetna.

The effect of repeated treatment with citalopram, (+)oxaprotiline, (-)oxaprotiline, imipramine and ECS on the turnover of dopamine D2 receptors in the rat brain was measured using an N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)-induced irreversible receptor inactivation method. Repeated treatment with citalopram and ECS, but not with (+) and (-) enantiomers of oxaprotiline and imipramine, significantly decreased the turnover of D2 receptors in the striatum. Neither of the applied repeated treatments changed the turnover of D2 receptors in the limbic system. The results suggest that changes in the turnover of D2 dopamine receptors in striatum may participate in the mechanism of antidepressant action of ECS and citalopram, but not that of (+) or (-)oxaprotiline or imipramine.

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citalopram Celexa
The putative 5-HT1B receptor agonist CP-93,129 suppresses rat hippocampal 5-HT release in vivo: comparison with RU 24969.

Hjorth S, Tao R.

Department of Pharmacology, University of Goteborg, Sweden.

We have compared the ability of the new putatively specific 5-HT1B receptor agonist CP-93,129 (3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b] pyrid-5-one) and the structurally related mixed 5-HT1A/5-HT1B receptor ligand RU 24969, to influence 5-HT release in brain in vivo, using microdialysis techniques in chloral hydrate-anaesthetised rats. CP-93,129 (3 or 10 microM, via the dialysis perfusion medium) caused a concentration-dependent and methiothepin (10 microM)-sensitive suppression of ventral hippocampal 5-HT output. The effect of RU 24969 on 5-HT output was dependent on whether or not the 5-HT reuptake blocker citalopram was present in the perfusion medium. Thus, RU 24969 (0.1 microM) induced a decrease, or an increase followed by a decrease (1 microM), in 5-HT output in the absence of citalopram, but monotonically decreased (1 microM) 5-HT release when citalopram (1 microM) was present. CP-93,129 decreased dialysate 5-HT in either condition. Our findings are consistent with the characterisation of CP-93,129 as a 5-HT1B receptor agonist, and may thus represent in vivo support for 5-HT1B autoreceptor-mediated feedback control of 5-HT release in the rat brain. The 5-HT1B selectivity of CP-93,129, and its lack of 5-HT reuptake blocking properties, suggests that the compound compares favourably with other purported 5-HT1B receptor agonists.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1797566&dopt=Abstract citalopram Celexa