SYNTHESIS AND MUSCARINIC PROPERTIES OF METHYL(1-METHYL-6-OXABICYCLO[3.1.0]HEX-3-YL)METHYL AMMONIUM IODIDE

To acquire more information about the so-called ''muscarinic subsite'' , compound 4 was synthesized and tested. The results show that in comp arison with deoxamuscarine (23) the muscarinic potency of 4 on M(2) an d M(3) subtypes is not significantly altered by the presence of an epo xidic function, which confirms the donor-acceptor hydrogen bonding cha racter of this receptive site. Conversely, there is a negative influen ce on the transduction processes. In addition, a second hydroxylic fun ction bound on the carbon carrying the terminal methyl of the fourth s ubstituent on the nitrogen dramatically affects the muscarinic behavio r; the resulting compounds (11-14) lack any agonist or antagonist acti vity.