PHARMACOLOGICAL CHARACTERIZATION OF THE VESAMICOL ANALOG (-[I-125]MIBT IN PRIMATE BRAIN())

The vesamicol analogue, meta-[I-125]iodobenzyltrozamicol [(+)-[I-125]M IBT] was evaluated as a probe for the in vitro labeling of the vesicul ar acetylcholine transporter in primate brain. In the striatum, (+)-[I -125]MIBT bound a single high-affinity site with a K-d value of 4.4 +/ - 0.7 nM. Competition for (+)-[I-125]MIBT binding to the striatum by a group of vesamicol analogues displayed a pharmacological profile simi lar to the rank order of potency previously observed for the vesicular acetylcholine transporter on Torpedo synaptic vesicles. High-affinity binding of (+)-[I-125]MIBT in the occipital cortex was characterized by a K-d value of 4.6 +/- 1.1 nM. However, the rank order of potency f or inhibition of (+)-[I-125]MIBT binding to the occipital cortex by th e same test compounds differed from that observed in the striatum. The results suggest that (+)-[I-125]MIBT is a reliable probe of the vesic ular acetylcholine transporter in primate striatum, but its binding in primate occipital cortex is more complex. (C) 1997 Elsevier Science B .V.