Distribution of chlorpromazine and imipramine in adipose and other tissues of rats

Bickel, Marcel H.; Graber, Brigitte E.; Moor, Markus

doi:10.1016/0024-3205(83)90742-7

Cited by 45 publications

(18 citation statements)

References 8 publications

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“…Immediate redistribution also occurs in the lungs, which kinetically belong to the blood compartment and contain speci®c Imip binding sites (Morin et al, 1984) similar to those in the brain (Raisman et al, 1979). The lung contained the highest concentrations of Imip of all the tissues examined, in agreement with previous reports (Dingell et al, 1964;Bickel et al, 1983). This accumulation in the lung is typical of basic lipophilic drugs.…”

Section: Discussionsupporting

confidence: 90%

Influence of various combinations of specific antibody dose and affinity on tissue imipramine redistribution

Ragusi

Boschi

Risède

et al. 1998

British J Pharmacology

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This study was designed to evaluate the distribution kinetics of imipramine (Imip) in the brain and the main peripheral organs (heart, kidney, liver and lung) of rats, and to establish the relationship between the redistribution of Imip from these tissues and the immunoreactive capacity (dose and affinity) of anti‐TCA IgG. [3H]‐Imip (1 nmol kg−1 body weight) was injected intravenously 6 min before the i.v. injection of antibodies. At this time, the concentrations of Imip and its main metabolites in plasma were determined. The radioactivity measured corresponded to 91.7% Imip, indicating that the pharmacokinetics reflected essentially Imip. Plasma and tissue Imip contents were measured over the interval 1 to 90 min in control and in treated rats. The antibodies used were a murine monoclonal IgG1 (Ka=3.8 107 M−1) at an IgG1/Imip molar ratio of 1000 (IgG1 1000), and a sheep polyclonal IgG (TAb, Ka=1.3 1010 M−1) at IgG/Imip molar ratios of 1, 10 and 100 (TAb1, TAb10 and TAb100). The anti‐TCA IgG increased the plasma [3H]‐Imip concentrations: the AUC1→60 min for [3H]‐Imip were 4 (IgG1 1000), 9 (TAb1), 33.9 (TAb10) and 41.4 (TAb100) times higher in the treated groups than in the controls. The opposite effect occurred in the brain, heart and lungs, with large, rapid decreases in Imip. The increase in plasma Imip and the decrease in tissue Imip depended on the immunoreactive capacity (NKa) of the antibody, where N=molar concentration of IgG binding sites and Ka=IgG affinity constant. Maximal plasma and tissue redistribution occurred when NKa=33.8×104. Imip redistribution can be controlled using various doses or affinities of specific antibodies, and the resulting rapid, extensive Imip redistribution from the main target organs could be very promising for TCA detoxification. British Journal of Pharmacology (1998) 125, 35–40; doi:10.1038/sj.bjp.0702033

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Section: Discussionsupporting

confidence: 90%

Influence of various combinations of specific antibody dose and affinity on tissue imipramine redistribution

Ragusi

Boschi

Risède

et al. 1998

British J Pharmacology

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“…Jori et al (1971) observed brain concentrations of imipramine and desipramine that were 6-17 times greater than those in plasma. After a 5 mg kg-1 intravenous dose, rat brain imipramine levels were 41 times higher than those in plasma (Bickel et al, 1983), reaching peak concentrations of 100 tiM. Desipramine concentrations in the brains of rats receiving 2.5-40mgkg-1 intraperitoneally ranged between 0.46 and 38 tigg of brain (1.7-140 tiM) (Hrdina & Dubas, 1981;Biegon & Samuel, 1979).…”

Section: Discussionmentioning

confidence: 99%

“…Inhibition of adenosine uptake can explain the enhanced release of labelled purine from guineapig cortical slices by desipramine (30-500 tiM) (Pull & Mcllwain, 1976;Sattin, 1981) and the theophylline-antagonized increase in cyclic AMP accumulation in guinea-pig cortical tissues by a number of antidepressants (Kodama et al, 1971;Huang & Daly, 1974;Sattin et al, 1978). Although these effects required concentrations in the 10-4M range, which are considerably higher than the 1 pM plasma levels typical of chronically treated patients, a number of animal and human studies have shown that the lipophilicity of these drugs can result in brain levels 10-40 times higher than plasma levels (Jori et al, 1971;Biegon & Samuel, 1979;Hrdina & Dubas, 1981;Kristinsson et al, 1983;Bickel et al, 1983). Thus brain levels in animals and patients treated with the tricyclic antidepressants could achieve the levels necessary for inhibition of adenosine uptake and enhancement of cyclic AMP formation.…”

Section: C) the Macmillan Press Ltd 1984mentioning

confidence: 99%

Potentiation of the action of adenosine on cerebral cortical neurones by the tricyclic antidepressants

Phillis

1984

British J Pharmacology

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1The effects of four tricyclic antidepressants, nortriptyline, iprindole, chlorimipramine and desipramine on adenosine-evoked depressions of the firings of rat cerebral cortical neurones has been studied. 2 When applied iontophoretically, all four substances enhanced the depressant actions of iontophoretically applied adenosine but did not affect the depressant actions of the uptake-resistant analogue, adenosine 5 '-N-ethylcarboxamide (NECA).3 Nortriptyline and iprindole administered intravenously (1 mg kg-') enhanced the depressant actions of iontophoretically applied adenosine. 4 When applied by larger iontophoretic currents, all four antidepressants inhibited the firing of cerebral cortical neurones. Chlorimipramine-and desimipramine-elicited depressions were antagonized by intravenously administered caffeine, an adenosine antagonist. 5 Earlier studies showed the tricyclic antidepressants inhibit the uptake of adenosine by rat brain cerebral cortical synaptosomes. The present results demonstrate that four antidepressants are able to potentiate the action of adenosine and that this occurs when these compounds are given in behaviourally meaningful doses. The specificity of the potentiation is demonstrated by the failure of these compounds to potentiate the depressant actions of an uptake-resistant analogue of adenosine, NECA. 6 Antagonism of the inhibitory effects of the antidepressants on neuronal firings by caffeine, indicates that these compounds can enhance the extracellular levels of endogenously released adenosine sufficiently to depress cell firing.

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“…1) -10 −6 M range (Cohen, 1983;Curry, 1983). Rats receiving comparable doses of neuroleptics typically develop 10-100 µM concentrations of drug in brain tissue (Bickel et al, 1983). In this study, SPMVs were exposed to concentrations of chlorpromazine spanning this range.…”

Section: Resultsmentioning

confidence: 99%

Effects of Chlorpromazine·HCl on the Structural Parameters of Bovine Brain Membranes

Jang

Jeong²,

Ahn³

et al. 2004

BMB Reports

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Fluorescence probes located in different membrane regions were used to evaluate the effects of chlorpromazine · HCl on structural parameters (transbilayer lateral mobility, annular lipid fluidity, protein distribution, and lipid bilayer thickness) of synaptosomal plasma membrane vesicles (SPMVs) isolated from bovine cerebral cortex. The experimental procedure was based on the selective quenching of 1,3-di(1-pyrenyl)propane (Py-3-Py) by trinitrophenyl groups, radiationless energy transfer from the tryptophan of membrane proteins to Py-3-Py, and energy transfer from Py-3-Py monomers to 1-anilinonaphthalene-8-sulfonic acid (ANS). In this study, chlorpromazine · HCl decreased the lateral mobility of Py-3-Py in a concentration dependent-manner, showed a greater ordering effect on the inner monolayer than on the outer monolayer, decreased annular lipid fluidity in a dose dependent-manner, and contracted the membrane lipid bilayer. Furthermore, the drug was found to have a clustering effect on membrane proteins.

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Distribution of chlorpromazine and imipramine in adipose and other tissues of rats

Cited by 45 publications

References 8 publications

Influence of various combinations of specific antibody dose and affinity on tissue imipramine redistribution

Influence of various combinations of specific antibody dose and affinity on tissue imipramine redistribution

Potentiation of the action of adenosine on cerebral cortical neurones by the tricyclic antidepressants

Effects of Chlorpromazine·HCl on the Structural Parameters of Bovine Brain Membranes

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