citalopram Celexa
Anxiolytic-like effects of escitalopram, citalopram, and R-citalopram in maternally separated mouse pups.

Fish EW, Faccidomo S, Gupta S, Miczek KA.

Department of Psychology, Tufts University, Medford, Massachusetts 02155, USA.

The S-enantiomer of citalopram, escitalopram, is a selective serotonin reuptake inhibitor (SSRI) that appears to be responsible for citalopram's antidepressant and anxiolytic effects. Clinically, escitalopram is reported to have fewer adverse side effects than do other SSRIs. This study compared escitalopram to other antidepressants in a preclinical procedure predicting anxiolytic-like effects of drugs. Carworth Farms Webster (CFW) mouse pups (7 days old) were separated from the dam and maintained at a temperature of 34 degrees C. Forty-five minutes after administering citalopram (0.56-10 mg/kg), escitalopram (0.0056-3 mg/kg), R-citalopram (1-10 mg/kg), paroxetine (0.3-3 mg/kg), fluoxetine (1-30 mg/kg), or venlafaxine (3-56 mg/kg) subcutaneously, the pups were placed individually on a 19.5 degrees C surface for 4 min. Ultrasonic vocalizations (USVs) (30-80 kHz), grid crossing, rolling (i.e., the pup turned on one side or its back), and colonic temperature were recorded. All the drugs reduced USV emission; escitalopram was the most potent (ED(50) 0.05 mg/kg), followed by paroxetine (0.17 mg/kg), citalopram (1.2 mg/kg), fluoxetine (4.3 mg/kg), R-citalopram (6 mg/kg), and venlafaxine (7 mg/kg). The doses that decreased USVs differed from those that increased motor activity. Increased grid crossing occurred after low doses of paroxetine (0.03 or 0.1 mg/kg) and fluoxetine (1 mg/kg), but only after the highest doses of the citalopram enantiomers and venlafaxine (0.3, 10, and 56 mg/kg, respectively). Except for escitalopram and venlafaxine, high doses of the treatments increased rolling. R-Citalopram caused a 10-fold rightward shift in escitalopram's dose-effect curve, suggesting that R-citalopram inhibits escitalopram's anxiolytic-like effects. These data support clinical findings that escitalopram is a potent, well tolerated SSRI with anxiolytic-like effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14593091&dopt=Abstract citalopram Celexa



citalopram Celexa
Effect of repeated treatment with antidepressant drugs or electroconvulsive shock (ECS) on the increase in food intake induced by clonidine injected into the paraventricular nucleus.

Przegalinski E, Jurkowska T.

Institute of Pharmacology, Polish Academy of Sciences, Krakow.

We studied the effect of antidepressant drugs (imipramine, amitriptyline, citalopram, mianserin: 10 mg/kg p.o. each; rolipram: 5 mg/kg p.o.) and ECS administered acutely and repeatedly (antidepressant drugs: twice daily for 21 days; ECS: once daily for 10 days) on the increase in food intake induced by clonidine (20 nmole) injected into the paraventricular nucleus of the hypothalamus in satiated rats. The response to clonidine was potentiated after repeated, but not acute, treatment with imipramine, while it was not modified following both acute and prolonged administration of amitriptyline. On the other hand, citalopram, mianserin and rolipram reduced the clonidine response after their acute and repeated administration; at the same time only 2 of these drugs (citalopram and rolipram) administered repeatedly produced such an effect in a drug-free period (i.e. 72 hr and 7 days after their last dose). A reduction of the clonidine-induced increase in food intake was observed following single and repeated application of ECS. Our results do not support the hypothesis that the subsensitivity of central alpha 2-adrenoceptors is a common feature of the prolonged antidepressant treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2833192&dopt=Abstract citalopram Celexa



citalopram Celexa
Long-term effect of antidepressant drugs and electroconvulsive shock on brain alpha 1-adrenoceptors following destruction of noradrenergic or serotonergic nerve terminals.

Nowak G, Przegalinski E.

Institute of Pharmacology, Polish Academy of Sciences, Krakow.

Antidepressant drugs and electroconvulsive shock (ECS) given repeatedly increase the density of brain alpha 1-adrenoceptors. However, the mechanism involved in this effect is unknown. To study the role of presynaptic noradrenaline (NA) and 5-hydroxytryptamine (5-HT) nerve terminals in the above phenomenon we examined the density of [3H]prazosin binding sites in the rat cerebral cortex following a prolonged treatment with imipramine and citalopram (10 mg/kg po, twice daily for 14 days) or ECS (once daily for 8 days) in animals pretreated with DSP-4 (62.5 mg/kg ip) and p-chloroamphetamine (PCA, 2 x 10 mg/kg ip). In normal rats imipramine, citalopram and ECS increased the density (Bmax) of [3H]prazosin binding sites by 30, 25 and 19%, respectively. DSP-4 pretreatment abolished the effect of imipramine and citalopram but not that of ECS. Pretreatment with PCA influenced the effect of neither antidepressant drugs nor ECS. Our results indicate that the "up-regulation" of alpha 1-adrenoceptors induced by imipramine and citalopram, but not by ECS, depends on intact NA nerve terminals. They also show that the 5-HT system is not involved in the above phenomenon.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2851781&dopt=Abstract citalopram Celexa



citalopram Celexa
Contrasting effects of citalopram and reboxetine on waking salivary cortisol.

Harmer CJ, Bhagwagar Z, Shelley N, Cowen PJ.

University Department of Psychiatry, Warneford Hospital, OX3 7JX, Oxford, UK.

RATIONALE: Acute administration of antidepressants which potentiate serotonin (5-HT) and noradrenaline (NA) function stimulates the hypothalamic-pituitary-adrenal (HPA) axis and increases salivary free cortisol in healthy subjects. The effects of repeated antidepressant administration have been less studied, but the ability of such treatment to modulate HPA axis activity may be relevant to therapeutic effects. OBJECTIVE: The objective of the study was to assess the effect of short-term treatment with two different antidepressant medications on HPA axis activity. METHODS: We studied the effect of 6-day treatment with the selective serotonin re-uptake inhibitor (SSRI) citalopram (20 mg daily) and the selective noradrenaline re-uptake inhibitor, reboxetine (8 mg daily), on diurnal salivary cortisol in a parallel group, placebo-controlled, double-blind design. RESULTS: Citalopram significantly enhanced the increase in salivary cortisol produced by waking, while the effect of reboxetine treatment was indistinguishable from placebo. There was no change in basal salivary cortisol levels sampled in a standard pattern throughout the day. CONCLUSIONS: Short-term treatment with citalopram and reboxetine produced strikingly different effects on waking salivary cortisol, arguing against a common effect of antidepressant drugs on HPA axis function. Waking salivary cortisol may be a more reliable means of assessing the effects of antidepressant treatment on the HPA axis than a standard regime of basal salivary sampling.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12605289&dopt=Abstract citalopram Celexa



citalopram Celexa
5-HT-uptake inhibition potentiates antinociception induced by morphine, pethidine, methadone and ketobemidone in rats.

Larsen JJ, Hyttel J.

The effect of the specific 5-HT-uptake inhibitor citalopram on the antinociception induced by morphine, pethidine, methadone and ketobemidone was examined in rats by means of the hot plate test. Further the 5-HT-uptake-inhibiting potency of these opioid-receptor stimulants was examined in vitro in rat brain synaptosomes. In doses devoid of antinociceptive activity, citalopram in a dose-dependent manner potentiated the antinociception induced by the four opioid analgesics. The potentiation of the ketobemidone-induced antinociception was not influenced by the spasmolytic agent A 29 (N,N-dimethyl-3,3-diphenyl-1-methylallylamine) which together with ketobemidone constitutes the active substances in Ketogan. The 5-HT-uptake-inhibiting potencies of the opioid receptor stimulants were from 21 to more than 56000 times lower than that of citalopram, the order of potency being methadone greater than pethidine greater than ketobemidone greater than morphine. The results support the suggested role of 5-HT in morphine-induced antinociception and indicate a similar role in the antinociceptive effect induced by other opioid-receptor stimulants.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2865865&dopt=Abstract citalopram Celexa



citalopram Celexa
The effect of antidepressants on ethylmorphine and imipramine N-demethylation in rat liver microsomes.

Daniel W, Melzacka M.

The effects of single and multiple doses of desipramine, amitriptyline or citalopram on the rat liver microsomal cytochrome P-450 level and on the rate of ethylmorphine and imipramine demethylation in-vitro have been investigated. Desipramine, amitriptyline or citalopram when given to rats as a single dose, did not affect the level of cytochrome P-450 in the liver microsomes, however, there was a tendency towards acceleration of imipramine, and particularly ethylmorphine, demethylation. Prolonged administration of desipramine and citalopram, but not amitriptyline, elevated the microsomal level of cytochrome P-450 and accelerated the rate of ethylmorphine demethylation. All the drugs investigated, when given chronically, inhibited the rate of imipramine demethylation. Since demethylation of ethylmorphine and imipramine in a CO atmosphere was inhibited by ca 90% for the former and only by 58% for the latter, it can be assumed that prolonged administration of the drugs investigated has two different effects on the oxygenase systems in rat liver microsomes: on the one hand they stimulate the cytochrome P450 oxygenase system involved in ethylmorphine demethylation and, on the other, they inhibit the other microsomal oxygenase system involved in demethylation of imipramine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2872321&dopt=Abstract citalopram Celexa



citalopram Celexa
Biochemical and pharmacological tests for the prediction of ability of monoamine uptake blockers to inhibit the uptake of noradrenaline in-vivo: the effects of desipramine, maprotiline, femoxetine and citalopram.

Pawlowski L, Nowak G.

Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.

The ability of desipramine and maprotiline (NA uptake inhibitors), as well as citalopram and femoxetine (5-HT uptake inhibitors) to protect mice against brain NA depletion induced by H 77/77 (4-alpha-dimethyl-m-tyramine), has been compared with their ability to counteract reserpine (2.5 mg kg-1)- or apomorphine (16 mg kg-1)-induced hypothermia and to potentiate TRH (40 mg kg-1)-induced hyperthermia in mice. While both NA uptake inhibitors antagonized the action of H 77/77, maprotiline being weaker than desipramine, femoxetine and citalopram were inactive. However, in contrast to citalopram, femoxetine was active in the other tests, being about twice as weak as maprotiline, which itself was several times weaker than desipramine in those tests. On the basis of the results obtained it is concluded that functional in-vivo tests for NA uptake inhibitors are more sensitive than the H 77/77 biochemical test; moreover, femoxetine, which in-vitro studies is less selective than citalopram, may inhibit the uptake of NA in-vivo.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2894425&dopt=Abstract citalopram Celexa



citalopram Celexa
Potentiation of 5-hydroxytryptamine (5-HT) responses by a 5-HT uptake inhibitor in pulmonary and systemic vessels: effects of exposing rats to hypoxia.

Wanstall JC, Fiore SA, Gambino A, Chess-Williams R.

School of Biomedical Sciences, Department of Physiology and Pharmacology, The University of Queensland, St Lucia, 4072 Brisbane, Queensland, Australia.

The aim was to determine whether uptake of 5-hydroxytryptamine (5-HT) by the 5-HT transporter (SERT) modulates contractile responses to 5-HT in rat pulmonary arteries and whether this modulation is altered by exposure of rats to chronic hypoxia (10% oxygen; 8 h/day; 5 days). The effects of the SERT inhibitor, citalopram (100 nM), on contractions to 5-HT were determined in isolated ring preparations of pulmonary artery (intralobar and main) and compared with data obtained in systemic arteries. In intralobar pulmonary arteries citalopram produced a potentiation (viz. an increase in potency, pEC(50)) of 5-HT. The potentiation was endothelium-dependent in preparations from normoxic rats but endothelium-independent in preparations from hypoxic rats. In main pulmonary artery endothelium-independent potentiation was seen in preparations from hypoxic rats but no potentiation occurred in preparations from normoxic rats. In systemic arteries, citalopram caused endothelium-independent potentiation in aorta but no potentiation in mesenteric arteries; there were no differences between hypoxic and normoxic rats. It is concluded that SERT can influence the concentration of 5-HT in the vicinity of the vasoconstrictor receptors in pulmonary arteries. The data suggest that in pulmonary arteries from hypoxic rats, unlike normoxic rats, the SERT responsible for this effect is not in the endothelium and, hence, is probably in the smooth muscle. The data are compatible with reports that, in the pulmonary circulation, hypoxia induces/up-regulates SERT, and hence increases 5-HT uptake, in vascular smooth muscle. The findings may have implications in relation to the suggested use of SERT inhibitors in the treatment of pulmonary hypertension.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14605793&dopt=Abstract citalopram Celexa