Substituted imidazo[1,2-b]pyridazines. New compounds with activity at central and peripheral benzodiazepine receptors.
A large range of substituted imidazo[1,2-b]pyridazines have been synthesized, and a number of potent ligands at central benzodiazepine (Bz) receptors on rat brain membranes have been identified in initial binding screens using [3H]diazepam. For those tested more extensively, binding studies conducted in the presence and absence of gamma-aminobutyric acid suggest that they were full receptor agonists. Some preliminary evidence was found suggesting some species selectivity, i.e. several of the compounds were more active in in vivo tests in rats than in mice. The agonist activity of these 2-phenyl (and substituted phenyl) imidazo[1,2-b]pyridazines is consistent with the model of Bz receptor ligands as proposed by Fryer [Raven Press, 1983, pp. 7-20]. Several compounds were identified which had more selective activity at peripheral-type (mitochondrial) Bz binding sites. Thus, substituted imidazo[1,2-b]pyridazines represent yet another class of low molecular mass compounds which have activity at Bz receptor sites.
Davies
L P
LP
Research School of Biological Sciences, Australian National University, Canberra.
Barlin
G B
GB
Ireland
S J
SJ
Ngu
M M
MM
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001667:Binding, Competitive; D003975:Diazepam / Q000494:pharmacology; D005442:Flumazenil / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D051379:Mice; D016548:Prosencephalon / Q000187:drug effects*; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D007093:Imidazoles; D011724:Pyridazines; D011963:Receptors, GABA-A; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D003975:Diazepam