+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Affinity modulation of [3H]imipramine, [3H]paroxetine and [3H]citalopram binding to the 5-HT transporter from brain and platelets



Affinity modulation of [3H]imipramine, [3H]paroxetine and [3H]citalopram binding to the 5-HT transporter from brain and platelets



European Journal of Pharmacology 206(3): 243-250



The dissociations of [3H]imipramine, [3H]paroxetine and [3H]citalopram from the 5-HT (serotonin 5-hydroxytryptamine) transporter were found to be markedly influenced by several drugs, although concentrations in the microM range were needed. Most of these drugs attenuated the dissociation rate, i.e. increased the affinity between the ligand and the binding site. A few increased the dissociation rate however. The binding of drugs to the affinity-modulating site was specific, although of low affinity and probably changing the conformation of the high-affinity binding site, thereby changing the fit between the ligand and the interacting amino acid side-chains. Although the drugs usually affected the dissociation rates of the three ligands in the same manner, there were some which had different effects on [3H]imipramine, [3H]paroxetine and [3H]citalopram. For example, 5-HT markedly attenuated the dissociation of [3H]imipramine, had a moderate effect on [3H]paroxetine and very little effect on [3H]citalopram dissociation. This indicates that the three ligands are bound to different domains on the 5-HT transporter. [3H]Citalopram dissociation from human brain and rat brain were differently affected by several drugs. Indalpine augmented the dissociation rate of the [3H]citalopram 5-HT transport complex in human brain but attenuated it in rat brain, thus revealing a species difference of the 5-HT transporter.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 039200595

Download citation: RISBibTeXText

PMID: 1830276

DOI: 10.1016/s0922-4106(05)80025-2


Related references

Affinity modulation of tritiated imipramine tritiated paroxetine and tritiated citalopram binding to the 5 ht transporter from brain and platelets. European Journal of Pharmacology Molecular Pharmacology Section 4(3): 243-250, 1991

Association of [3H]-imipramine and [3H]-paroxetine binding with the 5HT transporter in brain and platelets: relevance to studies in depression. Journal of Receptor Research 7(1-4): 499-521, 1987

Association of tritiated imipramine and tritiated paroxetine binding with the 5 ht transporter in brain and platelets relevance to studies in depression. Journal Of Receptor Research: 499-522, 1987

Inhibitory and regulatory binding sites on the rat brain serotonin transporter: molecular weight of the [3H]paroxetine and [3H]citalopram binding proteins. European Journal of Pharmacology 189(2-3): 129-134, 1990

Tritium labeled 2 nitro imipramine a selective slowly dissociating probe of the imipramine binding site serotonin transporter in platelets and brain. Life Sciences 32(6): 645-654, 1983

Inhibitory and regulatory binding sites on the rat brain serotonin transporter molecular weight of the tritiated paroxetine and tritiated citalopram binding proteins. European Journal of Pharmacology Molecular Pharmacology Section 3(2-3): 129-134, 1990

Chlorimipramine--but not imipramine--rapidly reduces imipramine--but not paroxetine--binding in human platelets. Clinical Neuropharmacology 9(Suppl. 4): 113-115, 1986

Antidepressant binding sites in brain: autoradiographic comparison of [3H]paroxetine and [3H]imipramine localization and relationship to serotonin transporter. Journal of Pharmacology and Experimental Therapeutics 252(1): 410-418, 1990

Regional distribution of specific high affinity binding sites for 3H-imipramine and 3H-paroxetine in human brain. Journal of Neural Transmission 104(1): 89-96, 1997

Regional distribution of the serotonin transport complex in human brain, identified with 3H-paroxetine, 3H-citalopram and 3H-imipramine. Progress in Neuro-Psychopharmacology and Biological Psychiatry 14(1): 61-72, 1990

High-affinity binding of 3H-imipramine in brain and platelets: relevance to depression and antidepressant drugs. Advances in Biochemical Psychopharmacology 31: 171-177, 1982

High-affinity binding of 3H-imipramine in brain and platelets and its relevance to the biochemistry of affective disorders. Life Sciences 29(3): 211-220, 1981

Antidepressant binding sites in brain autoradiographic comparison of tritiated paroxetine and tritiated imipramine localization and relationship to serotonin transporter. Journal of Pharmacology & Experimental Therapeutics 252(1): 410-418, 1990

3H]2-Nitroimipramine: a selective "slowly-dissociating" probe of the imipramine binding site ("serotonin transporter") in platelets and brain. Life Sciences 32(6): 645-653, 1983

3H] cocaine labels a binding site associated with the serotonin transporter in guinea pig brain: allosteric modulation by paroxetine. Neurochemical Research 17(12): 1275-1283, 1992