title: Rapamycin: brain excitability studied in vitro.
abstract: Neurological complications are common in transplant recipients treated with immunosuppressant calcineurin inhibitors. Rapamycin, a macrolide antibiotic, was suggested as an alternative agent in patients who develop calcineurin inhibitor associated neurotoxicity, including seizure attacks. The aim of the present study was to test the effect of rapamycin on the bioelectrical activity and evoked field excitatory postsynaptic potentials (fEPSP) in CA1 area of hippocampal tissues and compare its effect with FK506, a calcineurin inhibitor agent. Application of rapamycin at different concentrations neither affected the bioelectrical activity nor changed fEPSP magnitude. In contrast, FK506 elicited epileptiform burst discharges and significantly enhanced fEPSP magnitude. This study supports the suggestion that rapamycin could be used as an alternative to calcineurin inhibitors in the event of neurotoxicity.
authors.affiliation: Institut für Physiologie I, Westfälische Wilhelms-Universität Münster, Münster, Germany.
authors.forename: Delchad
authors.initials: D
authors.lastname: Daoud
authors.forename: Hans H
authors.initials: HH
authors.lastname: Scheld
authors.forename: Erwin-Josef
authors.initials: EJ
authors.lastname: Speckmann
authors.forename: Ali
authors.initials: A
authors.lastname: Gorji
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D019703:Calcineurin / Q000009:adverse effects / Q000627:therapeutic use; D065095:Calcineurin Inhibitors; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology; D005071:Evoked Potentials / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D006084:Graft Rejection / Q000517:prevention & control; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000517:prevention & control; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D020123:Sirolimus / Q000494:pharmacology*; D016559:Tacrolimus / Q000009:adverse effects / Q000494:pharmacology; D014180:Transplantation / Q000009:adverse effects / Q000379:methods
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D019703:Calcineurin; D020123:Sirolimus; D016559:Tacrolimus