Ketamine inhibition of ligand binding to cholinergic receptors and ion channels.

Ketamine inhibited the binding of [3H]perhydrohistrionicotoxin and [3H]phencyclidine to the ion channel associated with Torpedo acetylcholine receptors with ID50 values between 11 and 84 micro M, but had not effect on [3H]acetylcholine or [3H]d-tubocurarine binding to the receptor itself. Ketamine's affinity for the ion channel was increased 3-5 fold by receptor agonists. Ketamine also inhibited muscarinic cholinergic receptors with ID50 between 28 and 38 micro M. These results are consistent with biophysical evidence that ketamine interferes with neuromuscular transmission through blockade of the ion channel.