citalopram Celexa
Partial purification of the 5-hydroxytryptamine-reuptake system from human blood platelets using a citalopram-derived affinity resin [corrected]

Biessen EA, Horn AS, Robillard GT.

Department of Physical Chemistry, University of Groningen, The Netherlands.

This paper describes a procedure for the synthesis and application of a citalopram-derived affinity resin in purifying the 5HT-reuptake system from human blood platelets. A two-step scheme has been developed for partial purification, based on wheat germ agglutinin-lectin (WGA) affinity and citalopram affinity chromatographies. Upon solubilization of the carrier with 1% digitonin, a 50-70-fold increase in specific [3H]imipramine binding activity with a 70% recovery could be accomplished through WGA-lectin chromatography. The WGA pool was then subjected to affinity chromatography on citalopram-agarose. At least 90% of the binding capacity adsorbed to the column. Specific elution using 10 microM citalopram resulted in a 22% recovery of binding activity. A 10,000-fold overall purification was obtained by using this two-step procedure. Analysis of the fractions on SDS-PAGE after 125I labeling revealed specific elution of 78- and 55-kDa proteins concomitant with the appearance of [3H]imipramine binding activity. The pharmacological profile of the partially purified reuptake system correlated well with that derived from the crude membrane-bound reuptake system, suggesting a copurification of the 5HT binding activity and [3H]imipramine binding activity.

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citalopram Celexa
Serotonin autoreceptor subsensitivity and antidepressant activity.

Moret C, Briley M.

Centre de Recherche Pierre Fabre, Castres, France.

Release of [3H]serotonin elicited by electrical stimulation from rat hypothalamus and its modulation through autoreceptors has been studied after chronic administration of two antidepressants, citalopram, specific inhibitor of serotonin uptake, and milnacipran (previously called midalcipran, F 2207) which blocks the uptake of serotonin and noradrenaline to the same extent. The amount of [3H]serotonin released by electrical stimulation was enhanced and the inhibitory effect of the agonist, LSD (lysergic acid diethylamide), reduced in rats treated with citalopram at 10 and 50 mg/kg per day for 21 days. These effects existed at both doses but were accentuated at the higher dose. Thus a chronic treatment with citalopram provokes a down-regulation of the serotonergic autoreceptor, allowing an increase of serotonin neurotransmission. After 21 days treatment with milnacipran, at 50 mg/kg per day, none of the parameters studied were modified. These data suggest that down-regulation of the serotonin autoreceptor is not a universally applicable hypothesis to explain the action of all antidepressants acting on the uptake of serotonin.

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citalopram Celexa
Indoleamine metabolism in maturing mouse brain following extended uptake inhibition with citalopram.

Baker PC, Hoff KM.

Department of Biology, Cleveland State University, OH 44115.

1. At various ages between birth and adulthood mice were exposed to the specific uptake inhibitor citalopram (Lu 10-171) once a day for 5 days. 2. Their brains were assayed for 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) as well as indoleamine turnover at selected times after termination of the drug. 3. Younger brain differed from older brain in both stores and turnover. 4. Younger brain demonstrated the effects of citalopram action as much as 3 weeks later with continued elevation of 5-HIAA stores. 5. The possibility that 5-HIAA is an active agent in serotonergic neurogenesis is discussed.

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citalopram Celexa
Indoleamine stores in maturing mouse brain reexposed to citalopram following extended uptake inhibition.

Baker PC, Hoff KM.

Department of Biology, Cleveland State University, OH 44115.

1. Mice of various ages between birth and adulthood were injected daily for 5 days with the serotonin specific uptake inhibitor citalopram (LU 10-171). 2 days later they were reinjected with citalopram 2. 2 hr, 1 day and 3 days following the last injection animals were killed and their brains assayed for 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA). 3. Brains were found to still respond to citalopram's acute action despite the fact younger brains had undergone long term alteration of 5-HIAA stores. 4. The possibility that indoleamines are subject to different regulatory mechanisms in young brain is discussed.

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citalopram Celexa
Antinociceptive effects of serotonergic reuptake inhibitors in mice.

Fasmer OB, Hunskaar S, Hole K.

Department of Physiology, University of Bergen, Norway.

The antinociceptive effects of three predominantly serotonergic reuptake inhibitors, alaproclate, citalopram and clomipramine, were examined in mice using the hot-plate, formalin and substance P tests. The effects were compared with those of the noradrenergic reuptake inhibitor, desipramine. Different profiles in the three nociceptive tests were found for all four drugs, using doses of 10 and 40 mg/kg. The selective serotonergic reuptake inhibitor, alaproclate, seemed to have the least antinociceptive effects, and was the only drug that was ineffective in the hot-plate test. The other selective drug, citalopram, had a stronger effect than alaproclate in the substance P test, but in the formalin test, both drugs were approximately equally effective. Clomipramine differed from citalopram by being more effective in the formalin test. These findings thus indicate that selective inhibitors of the uptake of 5-HT have weaker antinociceptive effects than less selective drugs. Desipramine seemed to be no less effective than the serotonergic drugs and was the most potent drug in the hot-plate test.

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citalopram Celexa
Long-term effect of antidepressant drugs and electroconvulsive shock (ECS) on cortical alpha 1-adrenoceptors following destruction of dopaminergic nerve terminals.

Nowak G.

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

The effect of repeated treatment with imipramine, citalopram and ECS on the density of alpha 1-adrenoceptors in the cerebral cortex of rats with a dopaminergic lesion was studied. Imipramine and citalopram produced alph 1-upregulation in normal animals but not in animals with a dopaminergic lesion. On the other hand, ECS, produced such an effect in both normal and lesioned rats. Our results indicate that the investigated drugs (imipramine, citalopram) and ECS induce alpha 1-up-regulation via different mechanisms, and that the effect of these drugs depends on intact dopaminergic nerve terminals.

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citalopram Celexa
The effect of repeated administration of imipramine, citalopram and mianserin on responsiveness of central serotonergic, alpha 2-adrenergic and cholinergic system in mice.

Maj J, Rogoz Z, Skuza G, Sowinska H.

Institute of Pharmacology, Polish Academy of Sciences, Krakow.

The effect of antidepressant drugs: imipramine, citalopram and mianserin given either in a single dose or twice a day for 14 days in a dose of 10 mg/kg was investigated in mice in tests for the responsiveness of central serotonergic (L-5 hydroxytryptophan-induced head twitches), alpha 2-adrenergic (donidine hypoactivity) and cholinergic (oxotremorine syndrome) systems. The effect of L-5 hydroxytryptophan was inhibited by repeated administration of citalopram and mianserin but unchanged by administration of imipramine. After a single administration only mianserin inhibited the L-5 hydroxytryptophan effect. Given repeatedly, the investigated antidepressant drugs did not affect the effect of clonidine; only mianserin potentiated the hypoactivity when given in a single dose. Repeatedly administered antidepressant drugs did not affect the action of oxotremorine, although imipramine (but not citalopram or mianserin) antagonized it after a single administration. The results indicate that under the present conditions repeatedly given mianserin and citalopram, but not imipramine, antagonize behavioral effects of L-5 hydroxytryptophan. No one of the investigated antidepressant drugs given repeatedly changed the responsiveness of alpha 2 -adrenergic and cholinergic systems to their agonists. It might be concluded that the changes in alpha 1-adrenergic and dopaminergic systems, observed previously after repeated administration of antidepressant drugs, are selective.

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citalopram Celexa
Increase in endogenous 5-hydroxytryptamine levels modulates the central network underlying locomotion in the lamprey spinal cord.

Christenson J, Franck J, Grillner S.

Nobel Institute for Neurophysiology, Karolinska institutet, Stockholm, Sweden.

To investigate the effects of an endogenous release of serotonin (5-HT) in the lamprey spinal cord, in vitro, the 5-HT uptake-blocker citalopram (1-10 microM) was added to the bathing solution. Samples taken from the physiological solution through high-performance liquid chromatography (HPLC) showed that 5-HT was released from the spinal cord. To study the effect of this endogenous release of 5-HT on the spinal network generating locomotion, 'fictive locomotion' was induced by bath application of N-methyl-D-aspartate (NMDA, 100 microM). It elicited a steady locomotor rhythm between 0.2 and 2.5 Hz. The effects of citalopram were the following: (1) the locomotor frequency slowed down, (2) the intensity of the ventral root bursts was increased and (3) the intersegmental phase lag was prolonged. The effects of citalopram and thus presumably of an endogenous release of 5-HT were similar to what has previously been observed during bath application of 5-HT. In the latter case the conditions are different, since all 5-HT receptors regardless of their location in relation to the 5-HT-containing boutons will be affected in a similar way.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2668801&dopt=Abstract citalopram Celexa