A STUDY OF THE STRUCTURE-ACTION RELATIONSHIPS BETWEEN SOME SCOPOLIA ALKALOID DERIVATIVES AND THEIR EFFECTS ON MUSCARINIC RECEPTORS

The effects of a series of compounds related to scopolia alkaliods on specific binding of ³H-QNB to muscarinic receptor in rat brain were studied. The structureaction relationships of these compounds were analysed by comparing their IC₅₀ (determined by binding studies), dissociation constants K_B for drug-receptor interaction (derived from their abilities to antagonize Ach-induced ileum contraction), and their ED₅₀s of antitremorine and antipitocarpine-induced salivation effects in mice.Excellent correlation (r=0.977) was found between the logarithms of K_B and those of the corresponding IC₅₀ values. The slope of the regression line was 1. 047. The correlation between IC₅₀ and ED₅₀ of the antitremorine effect was poor, while the log IC₅₀/ED₅₀ (antitremor) values correlated well with their partition coefficient (log P)(r=0.971). Compound No. 10, with the best partition coefficient, was shown to have the highest selectivity on the CNS. The correlation coefficient of ED₅₀ (antisalivation) with IC₅₀ values was 0.827.