IMIDAZOLI(DI)NE COMPOUNDS INTERACT WITH THE PHENCYCLIDINE SITE OF NMDA RECEPTORS IN THE RAT-BRAIN

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