Synthetic and receptor binding studies on bicyclic annelated systems related to cyproheptadine
Gronowitz, S.; Westerlund, C.; Högberg, T.; Rämsby, S.; Hall, H.; Lindberg, U.H.
Acta Pharmaceutica Suecica 24(1): 1-14
1987
ISSN/ISBN: 0001-6675 PMID: 3618244 Document Number: 287135
A series of chloro substituted bicyclic 4-piperidylidene and 4-piperidyl derivatives has been investigated in order to assess the relative importance of the aromatic rings in tricyclic compounds of the cyproheptadine type. Determinations of in vitro activities of the new compounds were made in four receptor binding assays, i.e. dopamine-D2, muscarinic cholinergic, serotonergic 5-HT1 and 5-HT2, with cyproheptadine (1) and 3-bromocryproheptadine (2) as references. Generally the new compounds are less than 1 and 2. One carbinol derivative (17a) has a modest but selective affinity for the 5-HT2 receptor. The benzothiopyran 5a is about equipotent with 2 on binding to the 5-HT receptors, is 10-fold less active on the dopamine D2 receptor and is 50-fold less active on the muscarinic receptor, i.e. the bicyclic system offers a better 5-HT2 selectivity. The bicycles in general were found to be more active on 5-HT2 receptors than on dopamine-D2 receptors in spite of the halo substituent optimal for antidopaminergic effect in tricycles. Some of the new bicyclic derivatives retain certain degrees of binding affinity despite the fact that they are not optimally designed.