Anticholinergic activities of D(-)R- and L(+)S-mandeloylcholines.

The nature of the antagonism of the D(-)R- and L(+)S-mandeloylcholines to acetylcholine (ACh) was investigated at the muscarinic receptors of the guinea-pig ileal longitudinal muscle. The nature of the inhibition of acetylcholinesterase (AChE) and serum cholinesterase (ChE) by the mandeloylcholines was also investigated. Both optical isomers of mandeloylcholine were reversible competitive antagonists of ACh at the muscarinic receptors. One molecule of mandeloylcholine combined with one receptor. The apparent affinities (1/KB, where KB = dissociation constant) of the mandeloylcholines were in the following order: homatropine greater than D(-)R-mandeloylcholine greater than DL(+/-)RS-mandeloylcholines = L(+)S-mandeloylcholine. Therefore, the mandeloylcholines were stereoselective for muscarinic receptors. The mandeloylcholines were (mixed) reversible inhibitors (competitive and noncompetitive) of ACh hydrolysis by AChE. There was no significant difference between the apparent K1 values of the mandeloylcholines in the inhibition of AChE. The mandeloylcholines were mixed reversible inhibitors (competitive and noncompetitive) of ChE. D(-)R-mandeloylcholine had a higher apparent K1 than its isomer.