title: Memogain is a galantamine pro-drug having dramatically reduced adverse effects and enhanced efficacy.
abstract: Memogain (Gln-1062) is an inactive pro-drug of galantamine, the latter being a plant alkaloid approved for the treatment of mild to moderate Alzheimer's disease. Memogain has more than 15-fold higher bioavailability in the brain than the same doses of galantamine. In the brain, Memogain is enzymatically cleaved to galantamine, thereby regaining its pharmacological activity as a cholinergic enhancer. In animal models of drug-induced amnesia, Memogain produced several fold larger cognitive improvement than the same doses of galantamine, without exhibiting any significant levels of gastrointestinal side effects that are typical for the unmodified drug and other inhibitors of cholinesterases, such as donepezil and rivastigmin. In the ferret, dramatically reduced emetic and behavioral responses were observed when Memogain was administered instead of galantamine. Based on these and other preclinical data, Memogain may represent an advantageous drug treatment for Alzheimer's disease, combining much lesser gastrointestinal side effects and considerably higher potency in enhancing cognition, as compared to presently available drugs.
authors: Galantos Pharma GmbH, Freiligrathstrasse 12, 55131 Mainz, Germany. alfred.maelicke@galantos.com
authors: Alfred
authors: A
authors: Maelicke
authors: Anja
authors: A
authors: Hoeffle-Maas
authors: Juergen
authors: J
authors: Ludwig
authors: Arno
authors: A
authors: Maus
authors: Marek
authors: M
authors: Samochocki
authors: Ulrich
authors: U
authors: Jordis
authors: Andreas K E
authors: AK
authors: Koepke
mesh_terms: D000109:Acetylcholine / Q000819:agonists; D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005289:Ferrets; D005702:Galantamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D051379:Mice; D012601:Scopolamine / Q000037:antagonists & inhibitors; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors; C548757:memogain; D005702:Galantamine; D012601:Scopolamine; D000109:Acetylcholine