MUSCARINIC RECEPTOR SELECTIVITIES OF 3-QUINUCLIDINYL 8-XANTHENECARBOXYLATE (QNX) IN RAT-BRAIN

We have determined the binding of (R)-3-Quinuclidinyl 8-xanthenecarbox ylate to muscarinic acetylcholine receptor preparations from rat corte x, hippocampus, caudate/putamen, thalamus, pens and colliculate bodies . The competition curves determined with [H-3]quinuclidinyl benzilate as the radioligand are well described by a two site model with a diffe rence in affinity between the two sites of 12-fold. The proportions of high affinity site vary from 100% in the caudate/putamen to 0% in the pons/medulla. The selectivities are different from those measured by pirenzepine and are consistent with QNX exhibiting similar affinity fo r the M(1), M(3), and M(4) receptors with lower affinity for the M(2) receptor. This assignment was confirmed by determining the affinities of QNX for the cloned receptor subtypes.