Efflux studies allow further characterisation of the noradrenaline and 5-hydroxytryptamine transporters in rat lungs.

The aim of the present study was to further characterise the noradrenaline and 5-hydroxytryptamine [5-HT] transporters in rat lungs by examining the efflux of noradrenaline and 5-HT, respectively. Lungs from rats were isolated and perfused via the pulmonary artery. After loading the tissue with 3H-5-HT or 3H-noradrenaline the efflux of the relevant amine from the lungs was examined for 15-25 min. The rate constant for efflux of 3H-5-HT increased by 81% when Na+ ions were removed from the perfusion solution; increased gradually when a selective 5-HT transporter inhibitor, 200 nM Citalopram ( Celexa ), was added to the perfusion solution for the final 6 min of efflux; and increased markedly and rapidly when substrates of the 5-HT transporter, tryptamine (18 microM) and 7-methyltryptamine (12 microM), were added for the final 6 min of efflux. These effects of the substrates were abolished by 1 microM Citalopram ( Celexa ), but were not significantly affected by 1 microM desipramine, a selective uptake, inhibitor. On the other hand, the previously described substrate-induced increase in the rate of efflux of noradrenaline was significantly reduced by desipramine but was unaffected by Citalopram ( Celexa ). The results show that efflux of 5-HT is mediated only by the 5-HT transporter, with no significant contribution of uptake1, and efflux of noradrenaline from rat lungs is mediated only by uptake1 and not by the 5-HT transporter. The effects of dopamine on the efflux of noradrenaline over a concentration range of 100-600 nM were investigated and the results showed that 50% of the maximal increase in the rate of efflux occurred at a concentration of 275 nM. This value did not differ from the Km for uptake of dopamine. This result implies that the only factor affecting the substrate-induced increase in noradrenaline efflux is the affinity of the substrate for uptake1. The efflux of noradrenaline was also examined in the absence and presence of two concentrations of desipramine (0.35 and 1.5 microM). Analysis of these results showed that uptake1 contributed approximately 81% and diffusion 19% to the total efflux of noradrenaline and that 90% of the total noradrenaline efflux was subject to reuptake by uptake1 into the pulmonary endothelial cells.

The effect of Citalopram ( Celexa ) hydrobromide on 5-HT(2A) receptors in the impulsive-aggressive dog, as measured with (123)I-5-I-R91150 SPECT.

PURPOSE: Involvement of the serotonergic system in impulsive aggression has been demonstrated in both human and animal studies. The purpose of the present study was to investigate the effect of Citalopram ( Celexa ) hydrobromide (a selective serotonin re-uptake inhibitor) on the 5-HT(2A) receptor and brain perfusion in impulsive-aggressive dogs by means of single-photon emission computed tomography. METHODS: The binding index of the radioligand (123)I-5-I-R91150 was measured before and after treatment with Citalopram ( Celexa ) hydrobromide in nine impulsive-aggressive dogs. Regional perfusion was measured with (99m)Tc-ethyl cysteinate dimer (ECD). Behaviour was assessed before treatment and again after 6 weeks of treatment. RESULTS: A correlation was found between decreased binding and behavioural improvement in eight out of nine dogs. The 5-HT(2A) receptor binding index was significantly reduced after Citalopram ( Celexa ) hydrobromide treatment in all cortical regions but not in the subcortical area. None of the dogs displayed alterations in perfusion on the post-treatment scans. CONCLUSION: This study supports previous findings regarding the involvement of the serotonergic system in impulsive aggression in dogs in general. More specifically, the effect of treatment on the 5-HT(2A) receptor binding index could be demonstrated and the decreased binding index correlated with behavioural improvement.

Comparison of the effects of the selective serotonin-reuptake inhibitors Fluoxetine ( Prozac ), Paroxetine ( Paxil ), Citalopram ( Celexa ) and fluvoxamine in alcohol-preferring cAA rats.

Clinical studies indicate that selective serotonin-reuptake inhibitors (SSRIs) may decrease alcohol intake and craving in particular subgroups of alcoholics. The aim of the present study was to compare the behavioral profile of various SSRIs in alcohol-preferring cAA rats, a genetic model of alcoholism. The effects of acute IP administration of Fluoxetine ( Prozac ) (doses in mg/kg 1-10), Citalopram ( Celexa ) (3-30), fluvoxamine (3-30) and Paroxetine ( Paxil ) (1-10) on ethanol (EtOH) intake and preference, as well as food and total fluid intake, were determined in a 12-h access, water vs. 10% v/v EtOH two-bottle choice paradigm. Each compound reduced EtOH intake [Minimal Effective Doses (MEDs) 5, 10, 30 and 1 mg/kg for Fluoxetine ( Prozac ), Citalopram ( Celexa ), fluvoxamine, and Paroxetine ( Paxil ), respectively]. The degree of selectivity, that is, the extent to which reductions in EtOH intake could be separated from reductions in food and/or total fluid intake varied across the compounds. Thus, whereas EtOH intake was more markedly affected than food intake by Fluoxetine ( Prozac ), both parameters were equally affected by Citalopram ( Celexa ), and food intake was more markedly affected than EtOH intake by fluvoxamine and Paroxetine ( Paxil ). The anti-alcohol effect also differed with respect to specificity, that is, the degree to which effects on EtOH intake coincided with effects on EtOH preference. Whereas Fluoxetine ( Prozac ) showed the highest level of specificity, followed by Citalopram ( Celexa ) and fluvoxamine, the effect of Paroxetine ( Paxil ) was nonspecific. The observed variation in the degree of selectivity and specificity of the anti-alcohol effect of SSRIs suggests that reductions in EtOH intake are not merely a consequence of a general suppressive effect on consummatory behavior. It is hypothesized that differences between the behavioral profiles of these compounds reflect a differential involvement of 5-HT receptor subtypes.

Citalopram ( Celexa ) enhances the activity of chloroquine in resistant plasmodium in vitro and in vivo.

Citalopram ( Celexa ), is an extremely potent inhibitor of neuronal serotonin reuptake. It is structurally unrelated to other antidepressants, but it contains the chemical features associated with reversal of drug resistance and exhibits minimal cardiotoxic side effects and fewer of the anticholinergic and adrenolytic side effects associated with other psychotropic agents. Sensitivity tests to Citalopram ( Celexa ) alone and in combination with chloroquine were performed against chloroquine-resistant and chloroquine-sensitive strains of Plasmodium falciparum and Plasmodium chabaudi. Citalopram ( Celexa ) alone showed intrinsic activity against the chloroquine-resistant strains of P. falciparum (IC50 = 1.51 +/- .6 microM) but only limited activity against the chloroquine-sensitive strain (IC50 = 33.27 +/- 5.87 microM) and no activity in vivo. The interaction of chloroquine and Citalopram ( Celexa ) in vitro resulted in a synergistic response in the chloroquine-resistant strain but there was no interaction between the drugs in the chloroquine-sensitive strain--a pattern found with other reversal agents. Citalopram ( Celexa ) enhanced chloroquine susceptibility in both strains of P. chabaudi, however, the potentiating effect was seen at lower doses in the chloroquine-resistant strain. The results of this study suggest that Citalopram ( Celexa ) may have potential as a chemosensitizer in Plasmodium infections on the basis of the low toxicity of Citalopram ( Celexa ) at concentrations potentiating chloroquine activity both in vitro and in vivo.