Down regulation of dihydroalprenolol and imipramine binding sites in brain of rats repeatedly treated with imipramine

Kinnier, William J.; Chuang, De‐Maw; Costa, E.

doi:10.1016/0014-2999(80)90510-5

Cited by 92 publications

(22 citation statements)

References 20 publications

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“…In addition, a lower Kd value for 3H-CN-IMI than for 3H-IMI was observed in the present study. With both ligands we have found higher Bmax values than had previously been reported for untreated rats (Kinnier et al, 1980;Racagni et al, 1983;Raisman et al, 1980). Whether the tissue preparation could be responsible for such quantitative differences, which has also been shown to dramatically influence the maximal number of 3H-IMI binding sites in human thrombocytes (Friedlet al, 1983) and/or whether the amount of tissue used per sample could cause the differences, as suggested by Plenge and Mellerup (1982), remains to be determined.…”

Section: Discussioncontrasting

confidence: 37%

3H-imipramine and3H-cyano-imipramine binding in rat brain tissue: Effect of long-term antidepressant administration

Gentsch¹,

Lichtsteiner²,

Feer³

1984

J. Neural Transmission

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3H-imipramine and 3H-cyano-imipramine binding was determined in brain homogenates of rats which had been treated for 21 days with imipramine or desimipramine. When compared to control animals, long-term administration of these antidepressants did not induce any alteration in the maximal number of 3H-imipramine or 3H-cyano-imipramine binding sites. However, a transient increase in the apparent dissociation constant was observed. Such findings are discussed in respect to previous studies, which have been highly contraversial.

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Section: Discussioncontrasting

confidence: 37%

3H-imipramine and3H-cyano-imipramine binding in rat brain tissue: Effect of long-term antidepressant administration

Gentsch¹,

Lichtsteiner²,

Feer³

1984

J. Neural Transmission

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“…It is by now well documented in animal studies that previous administration of tricyclic antidepressants Kinnier et al 1980;Barbaccia et al 1983), inhibitors ofmonoamine oxidase activity (Zsilla et al 1983), haloperidol (Hrdina 1984) and lithium carbonate can affect significantly the density of [3H]-IMI binding sites in the rat brain. On the other hand, the results from human studies on the influence of antidepressant drugs on Bma x and Kd of [3H]-IMI binding in platelets of healthy volunteers or depressed patients do not provide a clear picture.…”

mentioning

confidence: 99%

Reduced Bmax of [3H]-imipramine binding to platelets of depressed patients free of previous medication with 5HT uptake inhibitors

et al. 1986

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The high-affinity binding sites for [3H]-imipramine (IMI) present in human platelets are associated with the neuronal uptake system for 5HT. It was recently demonstrated that previous antidepressant therapy with drugs which inhibit 5HT uptake could down-regulate [3H]-IMI binding and that this effect could persist up to 1 month after the end of treatment. We therefore re-examined the reported differences in Bmax of [3H]-IMI binding in platelets between control and depressed untreated patients, to evaluate the residual influence of previous antidepressant medication. The saturation characteristics of [3H]-IMI binding were compared in platelets from 17 depressed patients carefully selected according to previous antidepressant therapy and washout period, who were closely matched, for age and sex, with a group of control healthy volunteers. The results reveal a significant decrease by 47% in the Bmax of [3H]-IMI binding in platelets of untreated depressed patients when compared with controls. There was no significant modification of Kd values for platelet [3H]-IMI binding between the depressed and the control groups. Our results support the view that platelet [3H]-IMI binding is a useful tool as a biological marker in depression.

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“…An additional tool to study the mechanism of the down-regulation of /3-adrenergic receptors became available when Langer and his colleagues reported that specific Na+-dependent and highaffinity binding sites for [3H]imipramine are located in crude synaptic membranes prepared from various structures of mammalian brains (7,8). The maximal number, Bmax, of [3H]imipramine binding sites is down-regulated by repeated injections of imipramine or DMI (9)(10)(11). These recognition sites are located on 5HT axon terminals (12)(13)(14) and appear to be anatomically and functionally associated with the 5HT uptake mechanism (15)(16)(17).…”

mentioning

confidence: 99%

Modulation of neuronal serotonin uptake by a putative endogenous ligand of imipramine recognition sites.

Barbaccia¹,

Gandolfi²,

Chuang³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

121

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Imipramine inhibits the serotonin uptake by binding with high affinity to regulatory sites of this uptake located on axons that release serotonin. The number of imipramine recognition sites located on crude synaptic membrane preparations is reduced by two daily injections of imipramine or desmethylimipramine for 3 weeks. When the binding sites for [3H]imipramine are down-regulated the Vma of the neuronal uptake of serotonin is increased. Moreover, in minces prepared from the brain hippocampus of rats receiving imipramine in a dose regimen that reduces the number of [3H]imipramine recognition sites, the efficiency of imipramine as a blocker of the serotonin uptake is diminished. Hence the high-affinity binding sites for [3H]imipramine may have a physiological role in modulation of serotonin reuptake. Probably this is mediated by an endogenous effector of these regulatory sites. A nonpeptidic constituent of rat brain capable of displacing [3H]imipramine from its high-affinity binding site and of inhibiting the serotonin uptake in a dose-related manner has been extracted and its partial purification is described.Imipramine and desmethylimipramine (DMI) have been used for longer than two decades to relieve the symptoms of depression (1, 2). Their capacity to block norepinephrine (NE) and serotonin (5-hydroxytryptamine; 5HT) uptake has been considered to be important for their therapeutic action, but when it was noted that imipramine and DMI block amine uptake almost instantaneously, whereas their antidepressant action occurs with a latency time of 1-2 weeks (1), the importance of the uptake inhibition in explaining their therapeutic action was deemphasized. Upon repeated daily administration to rats imipramine and a number of its congeners down-regulate the function of NE recognition sites in several brain structures (3-6); because the onset of this down-regulation and that of the antidepressant action are delayed with respect to the beginning of the treatment, it has been suggested that the NE response downregulation and the antidepressant action may be related (6). An additional tool to study the mechanism of the down-regulation of /3-adrenergic receptors became available when Langer and his colleagues reported that specific Na+-dependent and highaffinity binding sites for [3H]imipramine are located in crude synaptic membranes prepared from various structures of mammalian brains (7,8). The maximal number, Bmax, of [3H]imipramine binding sites is down-regulated by repeated injections of imipramine or DMI (9-11). These recognition sites are located on 5HT axon terminals (12)(13)(14) and appear to be anatomically and functionally associated with the 5HT uptake mechanism (15)(16)(17).In 1981 at a symposium on the mode of action of antidepressants we reported that the selective destruction of 5HT axons by 5,7-dihydroxytryptamine (5,7-DHT), which eliminates[3H]imipramine recognition sites, prevented the down-regulation of f3-adrenergic recognition sites elicited by two daily injections of DMI repeated for 3 wee...

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Down regulation of dihydroalprenolol and imipramine binding sites in brain of rats repeatedly treated with imipramine

Cited by 92 publications

References 20 publications

3H-imipramine and3H-cyano-imipramine binding in rat brain tissue: Effect of long-term antidepressant administration

3H-imipramine and3H-cyano-imipramine binding in rat brain tissue: Effect of long-term antidepressant administration

Reduced Bmax of [3H]-imipramine binding to platelets of depressed patients free of previous medication with 5HT uptake inhibitors

Modulation of neuronal serotonin uptake by a putative endogenous ligand of imipramine recognition sites.

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