citalopram escitalopram Lexapro
Fluoxetine increases extracellular dopamine in the prefrontal cortex by a mechanism not dependent on serotonin: a comparison with citalopram.

Pozzi L, Invernizzi R, Garavaglia C, Samanin R.

Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.

Fluoxetine at 10 and 25 mg/kg increased (167 and 205%, respectively) the extracellular dopamine concentration in the prefrontal cortex, whereas 25 (but not 10) mg/kg citalopram raised (216%) dialysate dopamine. No compound modified dialysate dopamine in the nucleus accumbens. The effect of 25 mg/kg of both compounds on cortical extracellular dopamine was not significantly affected by 300 mg/kg p-chlorophenylalanine (PCPA) (fluoxetine, saline, 235%; PCPA, 230%; citalopram, saline, 179%; PCPA, 181%). PCPA depleted tissue and dialysate serotonin by approximately 90 and 50%, respectively, and prevented the effect of fluoxetine and citalopram on dialysate serotonin (fluoxetine, saline, 246%; PCPA, 110%; citalopram, saline, 155%; PCPA, 96%). Citalopram significantly raised extracellular serotonin from 0.1 to 100 microM (251-520%), whereas only 10 and 100 microM increased dialysate dopamine (143-231%). Fluoxetine similarly increased extracellular serotonin (98-336%) and dopamine (117-318%). PCPA significantly reduced basal serotonin and the effects of 100 microM fluoxetine (saline, 272%; PCPA, 203%) and citalopram (saline, 345%; PCPA, 258%) on dialysate serotonin but did not modify their effect on dopamine (fluoxetine, saline, 220%; PCPA, 202%; citalopram, saline, 191%; PCPA, 211%). The results clearly show that the effects of fluoxetine and of high concentrations of citalopram on extracellular dopamine do not depend on their effects on serotonin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10461894&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
The effects of acute and subchronic treatment with fluoxetine and citalopram on stimulus control by DOM.

Winter JC, Eckler JR, Doat MM, Rabin RA.

Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, 102 Farber Hall, Buffalo, NY 14214-3000, USA. jcwinter acsu.buffalo.edu

Previous reports from our laboratory have provided evidence that acute, i.e., concurrent, treatment with selective serotonin reuptake inhibitors (SSRIs) augments the stimulus effects of indoleamine and phenethylamine hallucinogens in the rat. In the present investigation, the acute effects of fluoxetine and citalopram on stimulus control induced by (-)-2,5-dimethoxy-4-methylamphetamine (DOM) were compared with those following subchronic, i.e., 10-day treatment with the SSRIs. Stimulus control was established using DOM (0.56 mg/kg; 75-min pretreatment time) in a group of 11 rats. A two-lever, fixed ratio 10, positively reinforced task with saline controls was employed. The effects of a range of doses of DOM when given alone were compared with those following both acute and subchronic pretreatment with fluoxetine and citalopram in combination with DOM. It was found that acute administration of fluoxetine and citalopram potentiated the stimulus effects of DOM. Furthermore, it was observed that the degree of potentiation was not diminished by treatment with either fluoxetine or citalopram for a period of 10 days. It is concluded that whatever adaptive changes may take place in response to a 10-day period of treatment with either citalopram or fluoxetine, these adaptations are independent of the mechanisms responsible for the potentiation of the stimulus effects of DOM by the SSRIs.

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citalopram escitalopram Lexapro
The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation.

Xia Z, Bergstrand A, DePierre JW, Nassberger L.

Department of Biochemistry, Wallenberg Laboratory, Stockholm University, Sweden. xia tuborg.biokemi.su.se

Some widely used antidepressants such as imipramine, clomipramine, and citalopram have been found to possess antineoplastic effects. In the present study, these compounds were found to induce apoptotic cell death in human acute myeloid leukemia HL-60 cells. Apoptosis induced by the antidepressants was identified by electron microscopy and conventional agarose gel electrophoresis and was quantitated by propodium iodide staining and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) via flow cytometry. Treatment with apoptosis-inducing concentrations of the antidepressants (80 microM imipramine, 35 microM clomipramine, or 220 microM citalopram) caused induction of caspase-3/caspase-3-like activity, which was monitored by the cleavage of poly(ADP-ribose) polymerase (PARP), the loss of the 32 kD caspase-3 (CPP32) precursor, and the cleavage of the fluorescent CPP32-like substrate PhiPhiLux. Pretreatment with a potent caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl-ketone (zVAD-fmk) inhibited antidepressant-induced CPP32/CPP32-like activity and apoptosis. Furthermore, activation of caspase induced by the antidepressants was preceded by the hypergeneration of intracellular reactive oxygen species (ROS). These results suggested that the antidepressants may induce apoptosis via a caspase-3-dependent pathway, and induction of apoptosis by the antidepressants may provide a clue for the mechanism of their antineoplastic effects.

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citalopram escitalopram Lexapro
Citalopram and desmethylcitalopram in vitro: human cytochromes mediating transformation, and cytochrome inhibitory effects.

von Moltke LL, Greenblatt DJ, Grassi JM, Granda BW, Venkatakrishnan K, Duan SX, Fogelman SM, Harmatz JS, Shader RI.

Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA.

BACKGROUND: Biotransformation of citalopram (CT), a newly available selective serotonin reuptake inhibitor antidepressant, to its principal metabolite, desmethycitalopram (DCT), and the capacity of CT and DCT to inhibit human cytochromes P450, were studied in vitro. METHODS: Formation of DCT from CT was evaluated using human liver microsomes and microsomes from cDNA-transfected human lymphoblastoid cells. Cytochrome inhibition by CT and DCT in liver microsomes was studied using isoform-specific index reactions. RESULTS: Formation of DCT from CT in liver microsomes had a mean apparent K(m) of 174 mumol/L. Coincubation with 1 mumol/L ketoconazole reduced reaction velocity to 46 to 58% of control values, while omeprazole, 10 mumol/L, reduced velocity to 80% of control. Quinidine produced minimal inhibition. DCT was formed from CT by heterologously expressed human P450-2D6, -2C19, -3A4. After accounting for the relative abundance of individual cytochromes, 3A4 and 2C19 were estimated to make major contributions to net reaction velocity, with a possible contribution of 2D6 at therapeutic CT concentrations. CT and DCT themselves produced negligible inhibition of 2C9, 2E1, and 3A, and only weak inhibition of 1A2, 2C19, and 2D6. CONCLUSIONS: Formation of DCT from CT is mediated mainly by P450-3A4 and 2C19, with an additional contribution of 2D6. CT at therapeutic doses in humans may produce a small degree of inhibition of P450-1A2, -2C19, and -2D6, but negligible inhibition of P450-2C9, -2E1, and -3A.

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citalopram escitalopram Lexapro
Synergistic actions of the 5-HT1A receptor antagonist WAY-100635 and citalopram on male rat ejaculatory behavior.

Ahlenius S, Larsson K.

Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden. sven.ahlenius fyfa.ki.se

The selective serotonin re-uptake inhibitor citalopram (0-40 mg kg(-1), s.c., - 60 min) did not affect the male rat ejaculatory behavior, and there were no statistically significant effects of the 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide 3HCl (WAY-100635) (0.04-0.08 mg kg(-1), s.c., - 30 min). When combined, there was a marked, and statistically significant, prolongation of the ejaculation latency in comparison with saline treated controls, as well as in comparison with either drug by itself. This citalopram (10.0)/WAY-100635 (0.04)-induced effect was fully antagonized by the administration of the 5-HT1B receptor antagonist isamoltane (4.0 mg kg(-1)). There were no consistent effects on other aspects of the male rat sexual behavior, i.e., number of mounts and intromissions preceding ejaculation and the post-ejaculatory interval. Finally, the intromission latency was also markedly enhanced in animals receiving both citalopram and WAY-100635, and at the higher dose of WAY-100635 (0.08 mg kg(-1)) 7 out of 18 animals failed to initiate copulation. It is suggested that blockade of inhibitory 5-HT1A autoreceptors discloses inhibitory effects of the selective serotonin re-uptake inhibitor citalopram on male rat ejaculatory behavior mediated via stimulation of 5-HT1B receptors.

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citalopram escitalopram Lexapro
Citalopram: new indication. No advantage.

[No authors listed]

(1) Citalopram, a serotonin reuptake inhibitor antidepressant, now has a new licensed indication, in the preventive treatment of panic attacks. In France, clomipramine, a tricyclic antidepressant, and paroxetine, another serotonin reuptake inhibitor, are already approved for this use. (2) In the only available comparative trial the efficacy of citalopram (20-60 mg/day) was similar to that of clomipramine (60-90 mg/day). (3) The safety profile of citalopram is different from that of clomipramine. (4) There are no data clearly comparing citalopram with paroxetine in terms of efficacy, safety, drug interactions, or convenience. (5) Clomipramine is much cheaper than citalopram.

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citalopram escitalopram Lexapro
Effects of the specific serotonin reuptake inhibitor, citalopram, upon local cerebral blood flow and glucose utilisation in the rat.

McBean DE, Ritchie IM, Olverman HJ, Kelly PA.

Faculty of Health Sciences, Queen Margaret University College, Clerwood Terrace, Edinburgh, UK. d.mcbean mail.qmced.ac.uk

The effects of the potent selective 5-HT reuptake blocking agent, citalopram (10 mg/kg, i.v.), on local cerebral blood flow (lCBF) and local cerebral metabolic rate of glucose (lCMRglu) were measured using [14C]iodoantipyrine (IAP) and [14C]2-deoxyglucose (2-DG) autoradiography, respectively. Significant decreases in lCBF were observed in nine of the 27 brain areas analysed, with significant decreases in lCMRglu observed in 17 areas. While decreases in blood flow were observed, it cannot be concluded that these were in fact the result of a direct action of 5-HT upon serotonergic receptors in cerebrovascular smooth muscle, since the dynamic relationship between flow and metabolism remains largely intact. The reductions in lCBF may be explained entirely by the secondary effects of depressed cerebral metabolic demand induced by citalopram which would, once again, question the role of specifically perivascular serotonergic nerve activity in the tonic control of cerebral blood flow.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10564738&dopt=Abstract citalopram escitalopram Lexapro