Organspecific, qualitative changes in the phospholipid composition of rats after chronic administration of the antidepressant drug desipramine

Moor, Markus; Honegger, Ulrich E.; Wiesmann, Ulrich

doi:10.1016/0006-2952(88)90553-9

Cited by 28 publications

(8 citation statements)

References 18 publications

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“…The lipid content of the brain is considerably higher than in other organs (Moor et al, 1988) and experimental evidence gathered in various animals and humans points to a dierential lipid content and composition in the grey and the white matters of the brain (Chavko et al, 1993;SoÈ derberg et al, 1990;Zhang et al, 1996). Total lipid content in the white matter is twice as high as in the grey matter.…”

Section: Introductionmentioning

confidence: 99%

Intracellular distribution of psychotropic drugs in the grey and white matter of the brain: the role of lysosomal trapping

Daniel

Wójcikowski

Pałucha

2001

British J Pharmacology

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1 Since the brain is not a homogenous organ (i.e. the phospholipid pattern and density of lysosomes may vary in its dierent regions), in the present study we examined the uptake of psychotropic drugs by vertically cut slices of whole brain, grey (cerebral cortex) and white (corpus callosum, internal capsule) matter of the brain and by neuronal and astroglial cell cultures. 2 Moreover, we assessed the contribution of lysosomal trapping to total drug uptake (total uptake=lysosomal trapping+phospholipid binding) by tissue slices or cells conducting experiments in the presence and absence of`lysosomal inhibitors', i.e., the lysosomotropic compound ammonium chloride (20 mM) or the Na + /H + -ionophore monensin (10 mM), which elevated the internal pH of lysosomes. The initial concentration of psychotropic drug in the incubation medium was 5 mM. 3 Both total uptake and lysosomal trapping of the antidepressants investigated (imipramine, amitriptyline,¯uoxetine, sertraline) and neuroleptics (promazine, perazine, thioridazine) were higher in the grey matter and neurones than in the white matter and astrocytes, respectively. Lysosomal trapping of the psychotropics occurred mainly in neurones where thioridazine sertraline and perazine showed the highest degree of lysosomotropism. 4 Distribution interactions between antidepressants and neuroleptics took place in neurones via mutual inhibition of lysosomal trapping of drugs. 5 A dierential number of neuronal and glial cells in the brain may mask the lysosomal trapping and the distribution interactions of less potent lysosomotropic drugs in vertically cut brain slices. 6 A reduction (via a distribution interaction) in the concentration of psychotropics in lysosomes (depot), which leads to an increase in their level in membranes and tissue¯uids, may intensify the pharmacological action of the combined drugs.

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Section: Introductionmentioning

confidence: 99%

Intracellular distribution of psychotropic drugs in the grey and white matter of the brain: the role of lysosomal trapping

Daniel

Wójcikowski

Pałucha

2001

British J Pharmacology

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“…The increase in membrane fluidity potentiates the turnover of enzymatic processes (Gavish & Werber 1989) as well as the rate of lateral encounters (Hanski et a1 1979) which, in turn, might facilitate the methylation of the membrane phospholipid. Although the modulation of phospholipid methylation by altering the level of the substrate (phosphatidylethanolamine) by imipramine cannot be excluded, the results of others (Lullmann-Rauch 1979; Honegger et al 1983; Moor et al 1988) indicate that only prolonged exposure of the tissue to imipramine or to other amphiphilic cationic agents led to phospholipidosis in the membrane.…”

Section: Regionmentioning

confidence: 98%

“…Treatment of rats with imipramine for fourteen days produced changes in the sensitivity of phospholipid methyltransferases to the stimulating effect of imipramine, since 5 x M imipramine added externally to the incubation mixture did not potentiate the phospholipid methylation in the synaptic cortical membranes of rats treated chronically with imipramine. Lullmann-Rauch (1979) and Moor et al (1988) have shown that-in contrast to short time expo-sure-long-term treatment with imipramine or desipramine led to the accumulation of phospholipid and induced marked differences in the phospholipid content of various tissues. Therefore, we cannot exclude the possibility that chronic exposure of rats to imipramine might decrease the level of substrate (phosphatidylethanolamine) or increase the level of the product (phosphatidylcholine) in the cortical membranes of rats and this could inhibit the stimulating effect of externally added imipramine.…”

Section: Regionmentioning

confidence: 99%

Effect of Imipramine on the Membrane Anisotropy and on the Phospholipid Methylation in the Central Nervous System of the Rat

Melzacka

Nocon

1991

Journal of Pharmacy and Pharmacology

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An ex-vivo and in-vitro study of the effects of imipramine on the membrane anisotropy and phospholipid methylation in the rat cortical membranes was carried out. A comparative study of the membrane fluidity in various brain regions indicated different basal anisotropy of the areas and different reaction of these membranes to imipramine. It was found that imipramine when given to rats chronically (14 x 10 mg kg-1, i.p.) or added externally to the cortical membranes of naive rats or rats treated with a single dose of imipramine (10 mg kg-1, i.p.) decreased the anisotropy of cortical membranes. Chronic imipramine produced some changes of the membrane architecture in the cortex, whereas imipramine in different concentrations did not fluidize these membranes in-vitro. Imipramine in concentrations corresponding to its mean concentration in the rat brain after administration at a dose of 10 mg kg-1 i.p., potentiated phospholipid methylation in the cortical membranes of naive rats and rats receiving imipramine in a single dose of 10 mg kg-1 i.p. in an in-vitro study, whereas the prolonged administration of imipramine decreased the sensitivity of phospholipid methyltransferases to the stimulating effect of the drug in-vitro.

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“…Indeed, Sklair-Tavron and Nestler [39] have shown that BDNF increases the survival and growth of hippocampal neurons. Animal studies have shown that imipramine antidepressants and their derivatives can behave as compounds that interact with G proteins [40]. Thus, it is plausible to hypothesize that depression could be considered a disorder of the super family of G-proteins coupled to a receptor.…”

Section: Antidepressant Action On Second Messengers and Genesmentioning

confidence: 99%

Are Antidepressants Mood Agents Or Anxiolytic Drugs?

Bourin¹

2018

SOJPPS

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Many advances have been made in the treatment of depression with the recent discovery of selective serotonin reuptake inhibitors (SSRIs) and mixed serotonin and norepinephrine reuptake inhibitors (SNRIs). Behavioral, electrophysiology, and microdialysis studies have shown that serotonin receptors, mainly the 5-HT1A, 5-HT1B, and 5-HT2C subtypes, play a key role in modulating antidepressant activity. The indirect activation of serotonergic receptors by antidepressants could lead, via an increase in 5-HT concentrations in the synapse of certain brain regions, to the activation of G proteins which would cascade the transcription of neurotrophic factor such as "the brainderived neurotrophic factor "(BDNF). Depression could be considered as an anomaly of transduction mechanisms, this hypothesis needs to be deepened by molecular biology studies. The fact that antidepressants are also active in the treatment of anxiety disorders, questions about the nature of their mechanism in these various pathologies.

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Organspecific, qualitative changes in the phospholipid composition of rats after chronic administration of the antidepressant drug desipramine

Cited by 28 publications

References 18 publications

Intracellular distribution of psychotropic drugs in the grey and white matter of the brain: the role of lysosomal trapping

Intracellular distribution of psychotropic drugs in the grey and white matter of the brain: the role of lysosomal trapping

Effect of Imipramine on the Membrane Anisotropy and on the Phospholipid Methylation in the Central Nervous System of the Rat

Are Antidepressants Mood Agents Or Anxiolytic Drugs?

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