New imidazo[1,2-b]pyridazine ligands for peripheral-type benzodiazepine receptors on mitochondria and monocytes.
Several 6-chloro-2,3-disubstituted imidazo[1,2-b]pyridazines, selected from a number of synthetic imidazo[1,2-b]pyridazines which lacked significant binding activity at central benzodiazepine receptors, potently inhibit [3H]diazepam, [3H]Ro5-4864 and [3H]PK11195 binding to rat kidney mitochondrial membranes. In membrane preparations from cultures of THP-1 cells, a human monocytic leukaemia cell line, the isoquinoline carboxamide PK11195 is strongly bound but the benzodiazepine ligands, diazepam and Ro5-4864, are much more weakly bound. The imidazopyridazine compounds which bind strongly to mitochondrial benzodiazepine receptors are very potent displacers of [3H]PK11195 bound to the THP-1 membranes. It appears that the binding properties of these new imidazopyridazine ligands at 'peripheral-type' benzodiazepine receptors resemble those of the isoquinoline carboxamides more than those of the benzodiazepines.
D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008024:Ligands; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D011724:Pyridazines / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*
D008024:Ligands; D011724:Pyridazines; D011963:Receptors, GABA-A