MUSCARINIC RECEPTOR PROBES BASED ON AMINE CONGENERS OF PIRENZEPINE AND TELENZEPINE

The N-methyl groups of pirenzepine and telenzepine (M1-antagonists) were modified to produce chemically functionalized N-alkyl analogs using a "functionalized congener" approach. The derivatives were tested in binding assays vs. [H-3]N-methylscopolamine in rat forebrain and cardiac membranes. The potency/selectivity were highly dependent on substitutions of the N-methyl group. The affinity in a series of n-alkyl amino derivatives progressively increased with the number of methylene groups. The amines were acylated with various reporter groups resulting in molecular probes of nanomolar affinity. The effect of chain length on aryl isothiocyanate affinity labels is explored.