The effects of several imidazoli(di)ne compounds on the binding of the non-competitive NMDA receptor antagonist [3H](+)-MK-801 (dizocilpine) to rat brain membranes were studied. These compounds fully inhibit radioligand binding with potencies in the micromolar range. The obtained profile of drug affinity correlated well with the potency of the same compounds promoting insulin release by blocking ATP-sensitive K+ channels in the rat insulinoma cell line RIN-5AH. It is suggested that imidazoli(di)ne compounds interact with cation channels sharing a common phencyclidine binding site (e.g. NMDA receptors, K+ channels and nicotinic acetylcholine receptors) and that this could be the basis of some biological effects of imidazoli(di)nes.