IMIDAZO[1,2-B]PYRIDAZINES .22. SYNTHESES OF SOME 2-ARYL-3-METHOXY-6-(PYRIDINYLMETHYLTHIO AND PYRIDINYLMETHYLAMINO)IMIDAZO[1,2-B]PYRIDAZINESAND THEIR INTERACTION WITH CENTRAL AND MITOCHONDRIAL (PERIPHERAL-TYPE) BENZODIAZEPINE RECEPTORS

2-Aryl-3-methoxy-6-(pyridinylmethylthio and pyridinylmethylamino)imida zo[1,2-b]pyridazines have been prepared and examined as ligands for be nzodiazepine receptors. Most were highly effective in displacing [H-3] diazepam from central benzodiazepine receptors present in rat brain me mbranes but showed little capacity for its displacement from mitochond rial (peripheral-type) benzodiazepine receptors present in rat kidney membranes. For example, ethoxy-2-(3',4'-methylenedioxyphenyl)-6-(pyrid in-2 ''-ylmethylthio)imidazo[1,2-b]pyridazine had an IC50 value of 1.7 nM for central receptors but gave only 39% displacement at 1000 nM fo r mitochondrial receptors. Of all the compounds described in this seri es of papers, 3-methoxy-6-(2'-methoxybenzylamino)-2-(3 '',4 ''-methyle nedioxyphenyl)imidazo[1,2-b]pyridazine was the most active in displaci ng [H-3]diazepam from central receptors (IC50 0.3 nM), and it had a lo w affinity for mitochondrial receptors (40% displacement of [H-3]diaze pam at 1000 nM).