Abstract
In the course of screening anticholinergic agents, tipepidine hibenzoate (Asverin®), a piperidine derivative with a tertiary ammonium nitrogen and a potent antitussive agent (1), was found to have a marked anticholinergic activity (2).
It is well known that among atropine and scopolamine derivatives, the anticholinergic activities of quaternary ammonium compounds are generally more potent than their tertiary derivatives (3). This also holds true with piperidine derivatives (2, 4). Therefore, efforts were made to search for an anticholinergic with strong spasmolytic activity among many quaternary ammonium derivatives of piperidine that would have minimal untoward effects, such as mydriasis and antisialagogue characteristics of most anticholinergics. As a result, a new compound, 1, 1-dimethyl-5-methoxy-3-(dithien-2-ylmethylene) piperidinium bromide (SA-504), was selected for further studies (2) (Fig. 1).
