THE PHARMACOLOGY OF 3-(N-PIPERIDYL)-1-PHENYL-1-CYCLOHEXYL-1-PROPANOL HCL (ARTANE) AND RELATED COMPOUNDS

New Antispasmodic Agents

¹ Lederle Laboratories Division, American Cyanamid Company, Pearl River, New York

1. The pharmacology of six compounds with the nucleus 3-(N-piperidyl)-1-phenyl-1-propanol with substituents on carbon atom number one has been investigated. The substituents were: cyclohexyl, phenyl, propyl, isopropyl, butyl and isoamyl.

2. The acute intravenous toxicity of these compounds in rats is of the same order of magnitude as that of atropine sulfate. In mice atropine sulfate is approximately one-half as toxic.

3. Extensive studies of chronic toxicity in mice, rats, guinea pigs, rabbits and dogs, did not reveal systemic changes attributable to multiple doses of these compounds.

4. All of the compounds are potent antispasmodics and in varying degrees exhibit other parasympatholytic effects. Like atropine sulfate they stimulate the central nervous system in high doses.

5. The isoamyl derivative, 267C, though the weakest spasmolytic in the group compares favorably with other synthetic antispasmodics. It has a low incidence of side actions and a wide margin between the effective antispasmodic dose and the excitant dose.

6. The strongest antispasmodic in this group is the cyclohexyl derivative, 275C, which approaches atropine sulfate in activity. In the lower doses the parasympatholytic effects are accompanied by a mild depression of the central nervous system and in large doses by excitement. The difference between the depressant dose and the excitant dose is large.