The complex of a bivalent derivative of galanthamine with torpedo acetylcholinesterase displays drastic deformation of the active-site gorge: implications for structure-based drug design.

Bifunctional derivatives of the alkaloid galanthamine, designed to interact with both the active site of the enzyme acetylcholinesterase (AChE) and its peripheral cation binding site, have been assayed with Torpedo californica AChE (TcAChE), and the three-dimensional structures of their complexes with the enzyme have been solved by X-ray crystallography. Differences were noted between the IC(50) values obtained for TcAChE and those for Electrophorus electricus AChE. These differences are ascribed to sequence differences in one or two residues lining the active-site gorge of the enzyme.

(-)-9-Dehydrogalanthaminium bromide, a new cholinesterase inhibitor, enhances place and object recognition memory in young and old rats.

In a previous study, we showed that (-)-9-dehydrogalanthaminium bromide, a synthetic galanthamine derivative, was more potent than galanthamine in inhibiting acetylcholinesterase. We studied here the action of this new compound on recognition memory in young and old rats, using a two-trial recognition task designed to test both place and object recognition. (-)-9-dehydrogalanthaminium bromide was injected (0.

Synthesis and structure-activity relationships of open D-Ring galanthamine analogues.

Open D-ring galanthamine analogues were prepared using ring-opening reactions of the quaternarized urethane or oxazolidine functions and were evaluated for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition potency.

Concise total synthesis of (+/-)-maritidine.

[reaction: see text] Maritidine can be readily obtained from the corresponding protected beta,gamma-unsaturated ketone. The quaternary carbon of maritidine was created for the first time via an intramolecular Heck reaction.

Combined treatment with galanthaminium bromide, a new cholinesterase inhibitor, and RS 67333, a partial agonist of 5-HT4 receptors, enhances place and object recognition in young adult and old rats.

The present study was designed to investigate whether a combination of a new acetylcholinesterase inhibitor we have synthesized, galanthaminium bromide, and an agonist of 5-hydroxytryptamine(4) receptors, RS 67333, at doses ineffective alone, improves performance in tasks involving place and object recognition memory. Dose responses of each compound were determined in order to select doses without effect alone. Accordingly, young adult rats were injected intraperitoneally with galanthaminium bromide (0.