citalopram escitalopram Lexapro
Up-regulation of beta 1-adrenergic receptors in rat brain after chronic citalopram and fluoxetine treatments.

Palvimaki EP, Laakso A, Kuoppamaki M, Syvalahti E, Hietala J.

Department of Pharmacology, University of Turku, Finland.

Quantitative receptor autoradiography was used to study the effects of the selective serotonin reuptake inhibitors citalopram and fluoxetine and the tricyclic antidepressant imipramine on the regulation of beta 1-adrenergic receptors in the rat brain. Rats were treated with saline, citalopram (10 mg kg-1), fluoxetine (10 mg kg-1), or imipramine (15 mg kg-1) SC once daily for 14 days. [125I]Iodocyanopindolol binding to beta 1-adrenergic receptors was found to increase significantly in the caudate-putamen and the somatosensory areas of the frontal cortex after both citalopram and fluoxetine treatments. Imipramine treatment elicited a marked decrease in beta 1 binding in the outer laminae of the cingulate cortex, as well as in the motor and somatosensory areas of the frontal cortex. In a separate experiment, rats were treated with saline, citalopram (2.5, 10 and 20 mg kg-1) or fluoxetine (2.5, 10 and 20 mg kg-1) SC once daily for 14 days. The effects of citalopram and fluoxetine on beta 1 receptors in the somatosensory cortex and caudate-putamen were replicated. These results demonstrate that chronic administration of selective serotonin reuptake inhibitors, in contrast to imipramine, can cause a regional up-regulation of beta 1-adrenergic receptors in the rat brain.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7871100&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
[3H]paroxetine and [3H]citalopram as markers of the human brain 5-HT uptake site: a comparison study.

Arranz B, Marcusson J.

Department of Geriatric Medicine, University of Linkoping, Sweden.

The binding of [3H]paroxetine and [3H]citalopram to the human brain serotonin (5-HT) uptake site has been characterized and compared. Our results reveal that the binding exclusively involved with the 5-HT uptake site is identical for both [3H]ligands. The selective 5-HT uptake inhibitor citalopram displays the highest affinity for this uptake site, as compared with the affinities obtained for desipramine and norzimeldine, which is in accordance with their respective blockage of 5-HT uptake. Similar Bmax values were obtained for both radioligands in the brain regions studied, indicating their binding to the same presynaptic membrane protein. Together these findings suggest that both [3H]paroxetine and [3H]citalopram are good markers of the 5-HT transporter as both bind selectively and with high affinity to the serotonin uptake sites. However, the higher affinity of [3H]paroxetine confirms that this compound is the best radioligand for the 5-HT uptake site available today.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7888147&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Alterations in dopamine and serotonin uptake systems in the striatum of the weaver mutant mouse.

Stotz EH, Palacios JM, Landwehrmeyer B, Norton J, Ghetti B, Simon JR, Triarhou LC.

Department of Psychiatry (Institute of Psychiatric Research), Indiana University School of Medicine, Indianapolis.

In the striatum of the homozygous weaver mutant mouse (wv/wv), dopamine content, uptake and tyrosine hydroxylase activity are decreased compared to wild-type (+/+) mice. In mice heterozygous for the weaver gene (wv/+), these dopaminergic parameters exhibit only minor reductions compared to +/+ mice. The wv/wv striatum has recently been shown to have an increase in serotonin content. In the present study, the serotonin uptake system of the weaver striatum was investigated. Synaptosomal uptake of [3H] serotonin was determined in the dorsal portion of wv/wv and +/+ striatum, and serotonin uptake sites were examined by the binding of [3H] citalopram in the striatum of wv/wv, wv/+ and +/+ mice. The dopamine uptake system was also investigated in all three genotypes via the binding of [3H] mazindol. Synaptosomal uptake of [3H] serotonin was increased by 79% in the dorsal portion of the wv/wv striatum compared to that seen in the +/+ striatum. The binding of [3H] citalopram was increased by 62% in the dorsolateral and by 111% in the dorsomedial portions of the wv/wv striatum compared to +/+. [3H] Citalopram binding in the wv/+ striatum was also higher than +/+, but this increase did not reach statistical significance. Within the wv/wv striatum, [3H] mazindol binding was almost completely absent (88-89% reduction) in the dorsal portion and severely reduced in the other striatal areas. These data support the notion that the dorsal portion of the wv/wv striatum, which has the severest reduction in dopamine uptake, is hyperinnervated by serotonin fibers.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7888149&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
The selective serotonin reuptake inhibitor citalopram induces the storage of serotonin in catecholaminergic terminals.

Suarez-Roca H, Cubeddu LX.

Pharmacology Section, Instituto de Investigaciones Clinicas, School of Medicine, University of Zulia, Maracaibo, Venezuela.

We investigated whether selective inhibition of serotonin (5-hydroxytryptamine; 5-HT) transporter with citalopram leads to accumulation of 5-HT in catecholaminergic neurons. In the rabbit olfactory tubercle, citalopram (1-10 microM) inhibited [(3)H]5-HT uptake; however, the maximal degree of inhibition achieved was 70%. Addition of nomifensine (1-10 microM) was required for complete inhibition of [(3)H]5-HT uptake. In slices labeled with 0.1 microM [(3)H]5-HT, cold 5-HT (0.03-1 microM) induced a large increase in the efflux (release) of stored [(3)H]5-HT, an effect blocked by coperfusion with 1 microM citalopram. Similar concentrations (0.03-1 microM) of norepinephrine (NE) or dopamine (DA) failed to release [(3)H]5-HT. When labeling with 0.1 microM [(3)H]5-HT was carried out in the presence of citalopram, 1) low concentrations of 5-HT failed to release [(3)H]5-HT; 2) DA and NE were more potent and effective in releasing [(3)H]5-HT than in control slices; 3) coperfusion of NE, DA, or 5-HT with citalopram enhanced the release of [(3)H]5-HT induced by the catecholamines but not by 5-HT; and 4) coperfusion of NE or DA with nomifensine antagonized NE- and DA-evoked [(3)H]5-HT release, with a greater effect on NE than on DA. These results suggest that in the rabbit olfactory tubercle, where there is coexistence of 5-HT, NE, and DA neurons, inhibition of the 5-HT transporter led to accumulation of 5-HT in catecholaminergic terminals. Thus, during treatment with selective serotonin uptake inhibitors (SSRIs), 5-HT may be stored in catecholaminergic neurons acting as a false neurotransmitter and/or affecting the disposition of DA and/or NE. Transmitter relocation may be involved in the antidepressant action of SSRIs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12065714&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Effect of indomethacin, renzapride, methysergide, ketanserin, granisetron and citalopram on serotonin-induced fluid accumulation in pig jejunum.

Hansen MB, Thorboll JE, Beubler E, Skadhauge E.

Department of Anatomy and Physiology, Royal Veterinary and Agricultural University, Kosice, Frederiksberg, Denmark.

The purpose of this study was to elucidate the intestinal serotonin (5-HT) receptor subtypes involved in fluid transport in the pig jejunum in vivo. The fluid accumulating effect of intraluminally administered 5-HT, renzapride, methysergide, ketanserin, granisetron, citalopram and intravenous indomethacin, was tested in tied-off loops in vivo. 5-HT caused a dose-dependent fluid accumulation, which was reduced by indomethacin by about 30%. Renzapride, methysergide, ketanserin, granisetron and citalopram all caused fluid accumulation. Taking into account these fluid accumulating effects, renzapride, methysergide, ketanserin and granisetron reduced the fluid accumulating effect of 5-HT, giving a maximal reduction of 70, 46, 76, and 80%, respectively. These data suggest the existence of intestinal 5-HT receptor subtypes involved in fluid transport in the pig jejunum. The antagonistic effects of indomethacin, ketanserin and granisetron, suggest the involvement of prostaglandins, as well as the 5-HT2 and the 5-HT3 receptor subtypes in the fluid accumulating response of 5-HT.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7918343&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Cyclic AMP and inositol phosphate accumulations in rat brain cortical slices following chronic citalopram or desipramine administration.

Sapena R, Morin D, Zini R, Tillement JP.

Department of Pharmacology, Faculty of Medicine of Paris XII, Creteil, France.

The influence of chronic administration of desipramine (16 mg/kg per day for 8 days) or citalopram (1 mg/kg per day for 8 days) on the serotonergic and noradrenergic stimulations of phosphoinositide hydrolysis and cyclic AMP formation was investigated in rat cerebral cortical slices. This was done by means of a prelabelling method allowing the simultaneous measurement of the accumulations of (3H) inositol phosphates ((3H)IP) and of (14C) cyclic AMP. Our results show that neither of the two drugs altered the inhibition of adenylate cyclase activity induced by serotonin1 (5-HT1) receptor agonists nor did they alter 5-HT1A and 5-HT1B receptor densities. Similarly they did not modify the stimulation of the inositol phosphate metabolism induced by 5-HT or norepinephrine (NE). Desipramine treatment decreased both beta-adrenoceptor-elicited cyclic AMP accumulation (-37%) and beta-adrenoceptor density (-29%), whereas citalopram was without effect. These results reinforce the idea that the ability of antidepressants to decrease the activity of the beta-adrenoceptor-adenylate cyclase complex is not common to all antidepressants, and provide no evidence for the involvement of 5-HT1A and/or 5-HT1B in the mechanism of action of these drugs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7956721&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Lack of 5-HT1A autoreceptor desensitization following chronic citalopram treatment, as determined by in vivo microdialysis.

Hjorth S, Auerbach SB.

Department of Pharmacology, University of Goteborg, Sweden.

Electrophysiological studies suggest that 5-HT autoreceptor desensitization may be responsible for the delayed clinical efficacy of some antidepressant drugs, such as selective 5-HT reuptake inhibitors (SSRI) and certain MAO inhibitors (MAOI). In the present study we have used in vivo microdialysis to test this hypothesis. Rats were treated for 2 weeks with the antidepressant SSRI citalopram (5 mg/kg, s.c., b.i.d.). After 24 hr withdrawal, dialysis probes were implanted in the dorsal hippocampus (DH) and the frontal cortex (FCx). The rats then received as acute challenge, a 5-HT1A autoreceptor-active dose of the reference 5-HT1A agonist 8-OH-DPAT (0.025 mg/kg s.c.). The 8-OH-DPAT-induced changes in dialysate 5-HT from the DH and the FCx were monitored and taken as an index of autoreceptor sensitivity. Chronic citalopram and control animals responded similarly to 8-OH-DPAT with a drop of 5-HT of about 50-65%; no significant difference between the chronic citalopram and control groups were obtained, either in the DH or in the FCx. These data suggest that cell body 5-HT1A autoreceptors do not desensitize in response to repeated administration with antidepressant SSRI drugs such as citalopram.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7984270&dopt=Abstract citalopram escitalopram Lexapro