title: Tacrine: In vivo veritas.
abstract: Tacrine was initially synthesised in 1945 as part of a project seeking antibacterial drugs to treat infected wounds in soldiers. However, it was inactive in vitro against common strains of bacteria. Serendipitously, it was injected in vivo into dogs anaesthetised with chloroform and morphine and noted to immediately counter the respiratory rate depression caused by morphine but not block analgesia. Subsequent studies showed that tacrine was an acetylcholinesterase inhibitor. When combined with morphine in ampoules it was possible to inject larger doses of morphine without causing respiratory depression and it was marketed for 10 years in Australia. Tacrine was also used alone for treating acute anticholinergic syndrome in the 1980s. Shortly after this, it was hypothesised by William Summers that it could be of benefit in treating the early stages of Alzheimer's dementia and an IND was granted by the US Food and Drug Administration and a use patent awarded to Summers. It was the first of four anticholinesterases to be approved for treating this condition although its variable pharmacokinetics was a disadvantage.
authors.affiliation: Florey Institute of Neuroscience & Mental Health, University of Melbourne, Parkville 3010, Australia. Electronic address: bevyn.jarrott@florey.edu.au.
authors.forename: Bevyn
authors.initials: B
authors.lastname: Jarrott
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D064807:Anticholinergic Syndrome / Q000188:drug therapy*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D013619:Tacrine / Q000494:pharmacology* / Q000627:therapeutic use*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D002800:Cholinesterase Inhibitors; D013619:Tacrine
keywords: Aminoacridine (PubChem CID:7019, acridin-9-amine); Antagonist of acute anticholinergic syndrome; Block of opiate-induced respiratory depression; Cholinesterase inhibitor; Oral treatment of Alzheimer’s dementia; Tacrine; Tacrine (PubChem CID:1935, 1,2,3,4-tetrahydroacridin-9-amine)