citalopram escitalopram Lexapro
Raphe 5-HT1A autoreceptors, but not postsynaptic 5-HT1A receptors or beta-adrenoceptors, restrain the citalopram-induced increase in extracellular 5-hydroxytryptamine in vivo.

Hjorth S, Bengtsson HJ, Milano S.

Department of Pharmacology, University of Goteborg, Sweden. Stephan.Hjorth pharm.gu.se

In vivo microdialysis in rat ventral hippocampus was used (i) to verify the importance of 5-HT1A autoreceptors in the raphe as targets for drugs that enhance the citalopram-induced elevation of forebrain 5-hydroxytryptamine (5-HT), and (ii) to further examine the specificity of (-)-penbutolol in this regard. The selective 5-HT1A receptor antagonist WAY100635 (s.c., or intra-raphe) or the mixed 5-HT1A/1B/beta-adrenoceptor antagonist (-)-penbutolol (s.c.), potentiated the citalopram-induced 5-HT rise, whereas local "reverse' dialysis of WAY100635 into the ventral hippocampus did not. Furthermore, the (-)-penbutolol-induced augmentation proved stereoselective and not mediated by beta-adrenoceptors (no effect of s.c. (+)-penbutolol, or beta 1- and beta 2-adrenoceptor blockers (betaxolol, ICI118.551)). These data provide direct evidence that increased stimulation of 5-HT1A autoreceptors in the midbrain raphe impedes the effect of citalopram on forebrain extracellular 5-HT, whereas neither postsynaptic 5-HT1A receptors nor beta-adrenoceptors appear to be involved.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8982649&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Increased noradrenaline efflux induced by local infusion of fluoxetine in the rat frontal cortex.

Hughes ZA, Stanford SC.

Department of Pharmacology, University College London, UK.

In microdialysis experiments in vivo, local infusion of either the selective serotonin reuptake inhibitor, fluoxetine, or the selective noradrenaline uptake inhibitor, desipramine, increased noradrenaline efflux in rat frontal cortex. Synaptosomal uptake of [3H]noradrenaline was used to test whether inhibition of uptake could contribute to this effect of fluoxetine. Low concentrations of fluoxetine were less effective than desipramine at inhibiting [3H]noradrenaline uptake; both compounds were more potent than the selective serotonin reuptake inhibitor, citalopram. To investigate whether this inhibition of uptake involved an action on noradrenergic neurones, experiments compared the effects of a noradrenergic lesion, induced by the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), on the inhibition of uptake by fluoxetine, desipramine and citalopram. The lesion reduced [3H]noradrenaline uptake in the presence of fluoxetine and citalopram but increased it in the presence of desipramine. The results suggest both that inhibition of noradrenaline uptake could contribute to the actions of fluoxetine and that a non-noradrenergic mechanisms is a target for this action.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8982723&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Effect of chronic administration of the selective serotonin (5-HT) uptake inhibitor citalopram on extracellular 5-HT and apparent autoreceptor sensitivity in rat forebrain in vivo.

Auerbach SB, Hjorth S.

Department of Biological Sciences, Rutgers University, Piscataway, NJ, USA.

Rats were administered the selective serotonin (5-HT) uptake blocker citalopram or saline for 14 days to determine if prolonged treatment would lead to changes in extracellular 5-HT or autoreceptor sensitivity. One day after drug withdrawal, dialysis probes were implanted in the frontal cortex and dorsal hippocampus. Dialysis experiments were carried out using chloral hydrate anesthetized rats. The experimental protocol comprised the administration of three consecutive drug challenges: (1) After stable baseline levels were obtained, citalopram was infused through the dialysis probes to locally block uptake in the forebrain. (2) Subsequently, a 5-HT1B receptor agonist (RU24969 or CP93,129) was infused through the probe to test for changes in terminal autoreceptor sensitivity. (3) Last, citalopram was administered systemically to test the effect of indirect activation of somatodendritic autoreceptors. Under these conditions, with uptake already blocked locally in the forebrain, systemic citalopram produces a decrease in extracellular 5-HT, an effect that can be inhibited by pretreatment with antagonists of 5-HT1A receptors. The results indicate that during local infusion of citalopram extracellular 5-HT was significantly higher in the dorsal hippocampus of the chronic citalopram as compared to saline treatment group. This difference persisted throughout the full time course of the experiment. However, the decreases in 5-HT levels produced by local infusion of a 5-HT1B receptor agonist or after systemic citalopram administration were not significantly different between the chronic citalopram and saline treated groups. There were no significant differences between chronic citalopram and saline treated animals in frontal cortex. These results suggest that prolonged inhibition of 5-HT uptake may produce a selective change in the regulation of release from median raphe 5-HT neurons, but this change could not be clearly linked to a change in nerve terminal or somatodendritic autoreceptor sensitivity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9053730&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Protective effect of citalopram against the attenuation of the alpha 1-potentiation of cAMP formation in Fischer 344 strain rats.

Izumi J, Washizuka M, Hayashi-Kuwabara Y, Yoshinaga K, Tanaka Y, Ikeda Y, Kiuchi Y, Oguchi K.

Central Research Laboratories, Zeria Pharmaceutical Co. Ltd., Saitama, Japan.

We investigated the effects of citalopram, a selective serotonin reuptake inhibitor (SSRI), using an animal model for a depressive state. In Fischer 344 rats, known as emotional animals, repeated stress by twice-daily intraperitoneal (i.p.) saline injections for 14 days elicited a depressive state characterized by a decreased open-field activity and a prolonged immobility during the tail-suspension test. Concomitantly, suppression of norepinephrine (NE)-induced cAMP formation was found in the cerebral cortical slices of the stress-exposed rats without changes in adrenergic alpha 1- or beta-receptors. The difference in cAMP formation between the intact and the stress groups was totally abolished under the blockade of the alpha 1-receptor system or by the stimulation with isoproterenol or forskolin, whereas the suppressed response in the stress group was also observed in combination with isoproterenol and phenylephrine. From these results, we confirmed that the potentiation of the beta-receptor-stimulated cAMP formation by the alpha 1-receptor is attenuated following repeated stress. Chronic i.p. administration of citalopram dissolved in saline improved both the suppressed open-field activity and the prolonged immobility in the tail-suspension test. The animals treated with citalopram exhibited a comparable alpha 1-potentiation effect as observed in the intact rats. However, another SSRI, paroxetine, was less effective on the attenuation of the alpha 1-potentiation in spite of its behavioral improvement in the depressive state. These findings suggest that citalopram has a protective effect against the repeated stress-induced depressive state by mechanisms besides the serotonin reuptake inhibition.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9062686&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Treatment of Interictal Depression with Citalopram in Patients with Epilepsy.

Hovorka J, Herman E, Nemcova I I.

Neurology and Neuropsychiatry Department, The Na Frantisku Hospital, Prague 1, Czech Republic

The purpose of this study is to assess the efficacy and safety of the selective serotonin-reuptake inhibitor (SSRI) citalopram in depressed epileptic patients. We evaluated 43 epileptic patients who suffered from depression and whose total score on the 21 items of the Hamilton Scale for Depression (HAMD 21) exceeded 15 points. These patients were examined by the psychiatrist and scaled before treatment and after 4 and 8 weeks of treatment with citalopram. The dose of citalopram was flexible, related to the actual condition of the patient. In each patient and in the whole group of patients we compared the monthly seizure frequency (total, partial seizures, generalized tonic-clonic seizures) recorded during treatment with citalopram with that recorded during the 2 months preceding the start of citalopram. During treatment we observed a decrease in the total score on the HAMD 21 from a mean initial value of 21.5 +/- 2.9 (range, 17-26) prior to therapy 14.5 +/- 2.9 (range, 10-19) (P < 0.001) after 4 weeks of treatment and to 9.9 +/- 3.1 (range, 4-19) (P < 0.001) after 8 weeks of treatment. There were 9 (20.9%) responders after 4 weeks of treatment and 28 responders (65.1%) after 8 weeks, all of them with decrease on the HAMD 21 greater than 50%. Nausea was the most common adverse event in 7 patients (16.3%) during the first month of treatment and in 3 patients (6.9%) during the second month of treatment. Sexual dysfunction (decrease of libido) was reported in 2 (4.7%) male patients during the entire course of treatment. No seizure worsening was observed in our patients. Monthly seizure frequency did not change significantly: 2.24 (+/-0.76) seizures before treatment with citalopram, 2.29 (+/-0.81) seizures in the first month of treatment, 2.21 (+/-1.00) seizures in the second month of treatment. No occurrence of de novo generalized tonic-clonic seizures was recorded in individual patients. Citalopram is a safe and effective antidepressant in the treatment of depressed epileptic patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12737834&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Sleep deprivation reduces the citalopram-induced inhibition of serotoninergic neuronal firing in the nucleus raphe dorsalis of the rat.

Prevot E, Maudhuit C, Le Poul E, Hamon M, Adrien J.

INSERM U288, CHU Pitie-Salpetriere, Paris, France.

Sleep deprivation (SD) for one night induces mood improvement in depressed patients. However, relapse often occurs on the day after deprivation subsequently to a sleep episode. In light of the possible involvement of central serotonin (5-hydroxytryptamine, 5-HT) neurotransmission in both depression and sleep mechanisms, we presently investigated, in the rat, the effects of SD and recovery sleep on the electrophysiological response of 5-HT neurons in the nucleus raphe dorsalis (NRD) to an acute challenge with the 5-HT reuptake blocker citalopram. In all rats, citalopram induced a dose-dependent inhibition of the firing of NRD neurons recorded under chloral hydrate anaesthesia. After SD, achieved by placing rats in a slowly rotating cylinder for 24 h, the inhibitory action of citalopram was significantly reduced (with a concomitant 53% increase in its ED50 value). After a recovery period of 4 h, a normal susceptibility of the firing to citalopram was restored. The decreased sensitivity of 5-HT neuronal firing to the inhibitory effect of citalopram after SD probably results in an enhancement of 5-HT neurotransmission. Such an adaptive phenomenon (similar to that reported after chronic antidepressant treatment), and its normalization after recovery sleep, parallel the mood improvement effect of SD and the subsequent relapse observed in depressed patients. These data suggest that the associated changes in 5-HT autocontrol of the firing of NRD serotoninergic neurons are relevant to the antidepressant action of SD.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9065875&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Behavioral profiles of SSRIs in animal models of depression, anxiety and aggression. Are they all alike?

Sanchez C, Meier E.

H. Lundbeck A/S, Copenhagen-Valby, Denmark.

The behavioral profiles of five clinically used selective serotonin reuptake inhibitors (SSRIs) citalopram, paroxetine, sertraline, fluvoxamine and fluoxetine, have been compared in animal models of antidepressant (mouse forced swim test), anxiolytic (exploration of black and white test box and foot-shock-induced ultrasonic vocalization in the rat) and antiaggressive (isolation-induced aggressive behavior in the mouse) activity. the results are discussed in relation to receptor binding data from the literature. Furthermore, affinities for the sigma 1 and sigma 2 binding sites are presented. Citalopram reversed the immobility induced by forced swimming with a potency similar to that of imipramine. Paroxetine, fluvoxamine and fluoxetine reversed swim-induced immobility less potently and with a maximum of 40-50% reversal. Citalopram produced a mixed anxiogenic-/anxiolytic-like response in rats tested in the two-compartment black and white box. Paroxetine induced an anxiogenic-like response at low doses and the other SSRIs were without major effects. Citalopram and paroxetine inhibited footshock-induced ultrasonic vocalization with high potencies. The dose-response curve was biphasic for citalopram with a maximum of 64% inhibition. Sertraline and fluvoxamine inhibited the vocalization less potently, and fluoxetine induced a weak inhibitory effect corresponding to a maximum of 32%. Sertraline, fluvoxamine and fluoxetine inhibited isolation-induced aggressive behavior, whereas citalopram and paroxetine were inactive. Both 5-HT1 and 5-HT2 receptors are involved, and there was a functional interaction between 5-HT1A and 5-HT2A or 5-HT2C receptors, as ritanserin potentiated the antiaggressive effect of 1,5-HTP as well as that of 8-OH-DPAT.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9084057&dopt=Abstract citalopram escitalopram Lexapro