Some properties of myeloid bodies induced in rat liver by an antidepressant drug (maprotiline)

Stäubli, W.; Schweizer, W; Suter, J.

doi:10.1016/0014-4800(78)90050-3

Cited by 15 publications

(4 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Subsequent leakage of proteolytic enzymes into the cytoplasm could damage myofibrils. However, other studies have failed to demonstrate that LLBs show altered permeability (Stäubli et al, 1978), and electron microscopy of myocytes in the present study did not show myofibrillar damage. The decisions to conduct toxicity studies required for clinical testing and to perform a variety of other activities accompanying development of a pharmaceutical candidate are accompanied by commitments that are time and resource intensive.…”

Section: Resultscontrasting

confidence: 88%

See 1 more Smart Citation

Myopathy Related to Administration of a Cationic Amphiphilic Drug and the Use of Multidose Drug Distribution Analysis to Predict its Occurrence

et al. 2004

View full text Add to dashboard Cite

Many cationic amphiphilic (phospholipidosis-inducing) drugs (CADs) accumulate in tissues following repeated dosing in preclinical models, and this is sometimes associated with dose-limiting toxicities. Plasma drug levels cannot be used to estimate tissue accumulation of CADs since it occurs in tissues despite stabilization of plasma levels. Severe myopathy was found in skeletal muscles of rats during the initial safety evaluation of a dopamine D3 receptor antagonist, PNU-177864, and was associated with phospholipidosis in numerous tissues. The myopathy was observed only when plasma levels of PNU-177864 remained essentially constant throughout the 24-hour dosing period. A repeat dose drug distribution study using whole body autoradiography demonstrated that drug-related material did not accumulate in skeletal muscle or other tissues following repeated doses at levels considered within the therapeutic range and showing toxicokinetic profiles acceptable for further development. These observations provided support for the continued development of and longer-term toxicity studies with this candidate compound.

show abstract

Section: Resultscontrasting

confidence: 88%

Section: Discussioncontrasting

confidence: 88%

Myopathy Related to Administration of a Cationic Amphiphilic Drug and the Use of Multidose Drug Distribution Analysis to Predict its Occurrence

et al. 2004

View full text Add to dashboard Cite

show abstract

“…The presence of lysosomal enzymes within DIM bodies in cells of different organs and species, after the administration of various AP drugs, has been repeatedly demonstrated (25,32,41,(99)(100)(101)(102). Quantitative studies usually reveal increased activities of acid phosphatase, ,-glucuronidase, 3-galactosidase, and decreased activities of acid esterase, ,-N-acetylglucosaminidase and cathepsin D (62,72,88,(103)(104)(105)(106)(107)(108).…”

Section: Biochemical Studiesmentioning

confidence: 98%

“…It indicates a generalized lysosomal storage of phospholipids. The drug-induced lysosomal storage differs from inborn lysosomal storage diseases (27,67,76,101). It has not been established whether administration of AP drugs to patients with lysosomal storage diseases will have adverse effects because of an additional increase in lysosomal volume.…”

Section: Pathologymentioning

confidence: 99%

Pulmonary and generalized lysosomal storage induced by amphiphilic drugs.

Hruban¹

1984

Environ Health Perspect

105

View full text Add to dashboard Cite

Administration of amphiphilic drugs to experimental animals causes formation of myelinoid bodies in many cell types, accumulation of foamy macrophages in pulmonary alveoli and pulmonary alveolar proteinosis. These changes are the result of an interaction between the drugs and phospholipids which leads to an alteration in physicochemical properties of the phospholipids. Impairment of the digestion of altered pulmonary secretions in phagosomes of macrophages results in accumulation of foam cells in pulmonary alveoli. Impairment of the metabolism of altered phospholipids removed by autophagy induces an accumulation of myelinoid bodies. The administration of amphiphilic compounds thus causes pulmonary intra-alveolar histiocytosis which is a part of a drug-induced lysosomal storage or generalized lipidosis. The accumulation of drug-lipid complexes in myelinoid bodies and in pulmonary foam cells may lead to alteration of cellular functioning and to clinical disease. Currently over 50 amphiphilic drugs are known. Unique pharmacological properties necessitate clinical use of some of these drugs. The occurrence and severity of potential clinical side effects depend on the nature of each drug, dosage and duration of treatment, simultaneous administration of other drugs and foods, individual metabolic pattern of the patient and other factors. Further studies on factors preventing and potentiating adverse effects of amphiphilic drugs are indicated.ImagesFIGURE 1.FIGURE 2.FIGURE 3.FIGURE 4.FIGURE 5.FIGURE 6.FIGURE 7.FIGURE 8.FIGURE 9.FIGURE 10.

show abstract

Toxicology of Antidepressant Drugs

Thomann¹,

Hess²

1980

Psychotropic Agents

View full text Add to dashboard Cite

Some properties of myeloid bodies induced in rat liver by an antidepressant drug (maprotiline)

Cited by 15 publications

References 38 publications

Myopathy Related to Administration of a Cationic Amphiphilic Drug and the Use of Multidose Drug Distribution Analysis to Predict its Occurrence

Myopathy Related to Administration of a Cationic Amphiphilic Drug and the Use of Multidose Drug Distribution Analysis to Predict its Occurrence

Pulmonary and generalized lysosomal storage induced by amphiphilic drugs.

Toxicology of Antidepressant Drugs

Contact Info

Product

Resources

About