Binding and functional properties of antimuscarinics of the hexocyclium/sila-hexocyclium and hexahydro-diphenidol/hexahydro-sila-diphenidol type to muscarinic receptor subtypes.

摘要: 1. In an attempt to assess the structural requirements for muscarinic receptor selectivity of hexahydro-diphenidol (hexahydro-difenidol) and hexahydro-sila-diphenidol (hexahydro-sila-difenidol), a series structurally related C/Si pairs were investigated, along with atropine, pirenzepine methoctramine, their binding affinities in NB-OK 1 cells as well rat heart pancreas. 2. The action these antagonists at receptors mediating negative inotropic responses guinea-pig atria ileal contractions has also been assessed. 3. Antagonist data indicated that (M1 type) (cardiac pancreas (glandular/smooth muscle possess different subtypes. 4. A highly significant correlation was found between pancreas, respectively, ileum. This implies sites are essentially similar, but from those 5. antimuscarinic potency three subtypes influenced differently by modifications (e.g. quaternization). Different profiles obtained, which makes compounds useful tools investigate further heterogeneity. Indeed, tertiary analogues (HHD) (HHSiD) had M1 = glandular/smooth greater than cardiac profile, whereas quaternary HHD methiodide HHSiD preferring muscle, cardiac).