부산대학교 도서관

The antidepressant drug opipramol has been reported to exert antilipolytic effect in human adipocytes, suggesting that alongside its neuropharmacological properties, this agent might modulate lipid utilization by peripheral tissues. However, patients treated for depression or anxiety disorders by this tricyclic compound do not exhibit the body weight gain or the glucose tolerance alterations observed with various other antidepressant or antipsychotic agents such as amitriptyline and olanzapine, respectively. To examine whether opipramol reproduces or impairs other actions of insulin, its direct effects on glucose transport, lipogenesis and lipolysis were investigated in adipocytes while its influence on insulin secretion was studied in pancreatic islets. In mouse and rat adipocytes, opipramol did not activate triglyceride breakdown, but partially inhibited the lipolytic action of isoprenaline or forskolin, especially in the 10-100 [mu]M range. At 100 [mu]M, opipramol also inhibited the glucose incorporation into lipids without limiting the glucose transport in mouse adipocytes. In pancreatic islets, opipramol acutely impaired the stimulation of insulin secretion by various activators (high glucose, high potassium, forskolin...). Similar inhibitory effects were observed in mouse and rat pancreatic islets and were reproduced with 100 [mu]M haloperidol, in a manner that was independent from alpha2-adrenoceptor activation but sensitive to Ca.sup.2+ release. All these results indicated that the anxiolytic drug opipramol is not only active in central nervous system but also in multiple peripheral tissues and endocrine organs. Due to its capacity to modulate the lipid and carbohydrate metabolisms, opipramol deserves further studies in order to explore its therapeutic potential for the treatment of obese and diabetic states.
Author(s): Maria Carmen Iglesias-Osma [sup.1] [sup.2], Maria José García-Barrado [sup.1] [sup.2], David Hernandez-Gonzalez [sup.1] [sup.2], Kévin Perrier [sup.3] [sup.4], Pénélope Viana [sup.3] [sup.4], Christian Carpéné [sup.3] [sup.4] Author Affiliations: (1) [...]