Studies on (/sup 3/H) hemicholinium-3 ((/sup 3/H)HC-3), (/sup 3/H) pirenzepine ((/sup 3/H)PZ) and (/sup 3/H)(-)quinuclidinyl benzilate ((/sup 3/H)(-)QNB) binding with choline and acetylcholine analogues (AF30, AF64, AF64A)

Choline deficiency in brain function has been implicated in several neurological disorders. Therefore, the usefulness of choline and its analogues as therapeutic agents or potential tools in developing selective models of central cholinergic hypofunction has been under investigation. The inhibitory potencies of ethylcholine mustard (AF64) and ethylcholine mustard aziridium (AF64A) were tested in inhibiting specific (/sup 3/H)HC-3 (rat striatal membranes), (/sup 3/H)PZ and (/sup 3/H)(-)QNB (cortical and heart membranes). AF64 and AF64A inhibited the binding of (/sup 3/H)HC-3 with low affinity. Results for one-site fit are: AF64: IC/sub 50/ = 107 ..mu..M, n/sub H/ = 0.62; AF64A: IC/sub 50/ = 130 ..mu..M, n/sub H/ = 0.56. Two site-fit resulted IC/sub 50/ values of 11-12 ..mu..M for high affinity and 360-730 ..mu..M for low affinity (relative proportions: 45% and 55%, respectively) in both cases. AF30 (a rigid choline analogue with agonist activity), AF64 and AF64A were weak inhibitors of muscarinic receptor bindings with IC/sub 50/ values in the micromolar range in both cortical and heart membranes, although AF64A showed ten-fold higher affinity in inhibiting (/sup 3/H)PZ binding than (/sup 3/H)(-)QNB binding in cortical membranes.