New analogs of physostigmine: alternative drugs for Alzheimer's disease?
The synthesis of a series of physostigmine analogs, in which the methylcarbamyl group has been substituted with monoalkylcarbamyl, dimethyl- and diethylcarbamyl groups, is reported. These compounds were prepared with the aim of investigating their possible therapeutic effects in the treatment of Alzheimer's type dementia. The new analogs of physostigmine are inhibitors of acetylcholinesterase from Electroforus electricus, with a value of the reactivation constant, k3 smaller than the one of physostigmine. The percentage of anticholinesterase activity in vitro and in vivo, the acute toxicity and some behavioural effects were also evaluated for selected derivatives. The reactivation constant, in vitro, supports the view that the derivatives described would be more suitable for therapeutic use than physostigmine.
Marta
M
M
Istituto di Chimica, Università Cattolica S.C. Facoltà di Medicina A. Gemelli, Rome, Italy.
Castellano
C
C
Oliverio
A
A
Pavone
F
F
Pagella
P G
PG
Brufani
M
M
Pomponi
M
M
D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000201:enzymology; D055598:Chemical Phenomena; D002621:Chemistry; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010830:Physostigmine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D012601:Scopolamine / Q000494:pharmacology; D013329:Structure-Activity Relationship
D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010830:Physostigmine; D012601:Scopolamine