Buccafusco_1988_Neuropharmacol_27_227

The purpose of this study was to determine whether a series of analogs of choline depress central cholinergic function in a manner consistent with the activity of their acetylated derivatives. Intracerebroventricular infusion of monoethylcholine (MECh), diethylcholine (DECh) and triethylcholine (TECh) inhibited the pressor response of unanesthetized rats to the subsequent intravenous injection of physostigmine (a well-characterized muscarinic response). The order of blocking potency was TECh greater than DECh greater than MECh greater than choline, directly opposite to the order of potency for elicitation of a central pressor response by their associated acetylated derivative (i.e. ACh greater than AMECh greater than ADECh = ATECh; Aronstam, Marshall and Buccafusco, 1988). In contrast, there was little selectivity between the analogs of choline in terms of their affinity for muscarinic receptors in the brainstem or cortex; the Ki's for inhibition of the binding of [3H]quinuclidinyl benzilate ranged from 0.33 to 0.95 mM). In terms of their affinity for nicotinic receptors (from the electric organ of Torpedo californica) the following order of potency was obtained: choline greater than MECh = DECh greater than TECh. Choline and MEC stimulated the binding of [3H]phencyclidine to the nicotinic ion channel (EC50's = 79 and 115 microM, respectively). At greater concentrations, all of the analogs inhibited ligand binding to the channel (Ki's from 0.2 to 10 mM), with the following order of potency: TECh greater than DECh greater than MECh greater than choline. These findings suggest that the inhibitory actions of these analogs of choline are related to their synthesis and release as false cholinergic neurotransmitters.