zimeldine and Lipidoses

The side effect profile and safety of fluoxetine are reviewed. Side effects reported more frequently with fluoxetine than with tricyclic antidepressants are nausea, nervousness, and insomnia. Anticholinergic side effects are reported less often with fluoxetine. Analysis of adverse experiences leading to discontinuations suggests that this drug has very few serious side effects. There is no evidence that fluoxetine produces a flu-like syndrome or neuropathy similar to that seen with zimelidine. It does not appear to cause phospholipidosis in humans. Fluoxetine appears to have no epileptogenic potential except at extremely high doses. It is usually well tolerated in overdoses.

Topics: Adult; Akathisia, Drug-Induced; Antidepressive Agents, Tricyclic; Cardiovascular Diseases; Clinical Trials as Topic; Drug Eruptions; Female; Fluoxetine; Humans; Influenza, Human; Lipidoses; Male; Middle Aged; Nausea; Nervous System Diseases; Patient Dropouts; Phospholipids; Placebos; Propylamines; Psychoses, Substance-Induced; Seizures; Sleep Initiation and Maintenance Disorders; Suicide, Attempted; Vision Disorders; Zimeldine

The side effect profile and safety of fluoxetine are reviewed. Side effects reported more frequently with fluoxetine than with tricyclic antidepressants are nausea, nervousness, and insomnia. Anticholinergic side effects are reported less often with fluoxetine. Analysis of adverse experiences leading to discontinuations suggests that this drug has very few serious side effects. There is no evidence that fluoxetine produces a flu-like syndrome or neuropathy similar to that seen with zimelidine. It does not appear to cause phospholipidosis in humans. Fluoxetine appears to have no epileptogenic potential except at extremely high doses. It is usually well tolerated in overdoses.

Topics: Adult; Akathisia, Drug-Induced; Antidepressive Agents, Tricyclic; Cardiovascular Diseases; Clinical Trials as Topic; Drug Eruptions; Female; Fluoxetine; Humans; Influenza, Human; Lipidoses; Male; Middle Aged; Nausea; Nervous System Diseases; Patient Dropouts; Phospholipids; Placebos; Propylamines; Psychoses, Substance-Induced; Seizures; Sleep Initiation and Maintenance Disorders; Suicide, Attempted; Vision Disorders; Zimeldine

Phospholipidosis is an adverse effect caused by numerous cationic amphiphilic drugs and can affect many cell types. It is characterized by the excess accumulation of phospholipids and is most reliably identified by electron microscopy of cells revealing the presence of lamellar inclusion bodies. The development of phospholipidosis can cause a delay in the drug development process, and the importance of computational approaches to the problem has been well documented. Previous work on predictive methods for phospholipidosis showed that state of the art machine learning methods produced the best results. Here we extend this work by looking at a larger data set mined from the literature. We find that circular fingerprints lead to better models than either E-Dragon descriptors or a combination of the two. We also observe very similar performance in general between Random Forest and Support Vector Machine models.

Topics: Animals; Artificial Intelligence; Databases, Factual; Drug Discovery; Humans; Lipidoses; Models, Biological; Phospholipids; Support Vector Machine

This study was aimed at the question of whether or not the antidepressant zimelidine, which is an amphiphilic cationic compound, can induce generalized lipidosis in animals. Rats were chronically treated with high oral doses (80 mg/kg) of the drug, and several organs were examined by light and electron microscopy. Lipidosis-like cellular alterations of considerable degrees were observed in lung, adrenal cortex and lymphatic tissue. Only mild lysosomal alterations were found in hepatocytes, adrenal medulla, retinal pigment epithelium and in peripheral and central nerve cell perikarya. The results show that zimelidine induces generalized lipidosis in rats although of mild degree when compared with some other amphiphilic cationic drugs.

Topics: Adrenal Cortex; Animals; Antidepressive Agents; Brompheniramine; Lipidoses; Lung; Lymph Nodes; Male; Pigment Epithelium of Eye; Pyridines; Rats; Zimeldine