ArticleBritish journal of pharmacology2001
Intracellular distribution of psychotropic drugs in the grey and white matter of the brain: the role of lysosomal trapping.
Article in British journal of pharmacology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 59 citations in OpenAlex.
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- Differential cytotoxicity responses by dog and rat hepatocytes to phospholipogenic treatments.Journal of toxicology · 2013Article
- Low-dose amitriptyline-induced acute dystonia in a patient with metachromatic leukodystrophy.JIMD reports · 2013Article
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- Cationic amphiphilic drugs cause a marked expansion of apparent lysosomal volume: implications for an intracellular distribution-based drug interaction.Molecular pharmaceutics · 2012Article
- Phospholipogenic pharmaceuticals are associated with a higher incidence of histological findings than nonphospholipogenic pharmaceuticals in preclinical toxicology studies.Journal of toxicology · 2012Article
- The subcellular distribution of small molecules: from pharmacokinetics to synthetic biology.Molecular pharmaceutics · 2011Review
- An intercalation mechanism as a mode of action exerted by psychotropic drugs: results of altered phospholipid substrate availabilities in membranes?Journal of chemical biology · 2010Article
- Modeling kinetics of subcellular disposition of chemicals.Chemical reviews · 2009Review
- Simulation-based cheminformatic analysis of organelle-targeted molecules: lysosomotropic monobasic amines.Journal of computer-aided molecular design · 2008Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
1. Since the brain is not a homogenous organ (i.e. the phospholipid pattern and density of lysosomes may vary in its different 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 microM), which elevated the internal pH of lysosomes. The initial concentration of psychotropic drug in the incubation medium was 5 microM. 3. Both total uptake and lysosomal trapping of the antidepressants investigated (imipramine, amitriptyline, fluoxetine, 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 differential 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 fluids, may intensify the pharmacological action of the combined drugs.
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