title: Anticholinesterasic drugs: tacrine but not physostigmine, accumulates in acidic compartments of the cells.
abstract: Tacrine (THA) and physostigmine (PHS) have been used in Alzheimer's disease therapy for their anticholinesterasic activity. Here we show that THA is taken up in rat lysosomes in an energy-dependent manner, and that it is also accumulated in acidic compartments of rat thymocytes and neuroblastoma cells. A concentration of THA less than 1 mM dissipated the pH gradient (delta pH) in all the above mentioned in vitro systems. On the contrary higher concentrations of PHS (1-2 mM) were ineffective. The accumulation of THA in acidic organelles of the cell may be relevant for the pharmacological action of THA in Alzheimer's treatment.
authors.affiliation: Dipartimento di Scienze Biomediche Sperimentali, Università and di Padova, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Dell'Antone
authors.forename: M
authors.initials: M
authors.lastname: Bragadin
authors.forename: P
authors.initials: P
authors.lastname: Zatta
mesh_terms: D000165:Acridine Orange / Q000493:pharmacokinetics; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active; D002460:Cell Line; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D051379:Mice; D015388:Organelles / Q000378:metabolism; D010830:Physostigmine / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000378:metabolism; D013619:Tacrine / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D013619:Tacrine; D010830:Physostigmine; D000165:Acridine Orange