Antagonism of interleukin-1 (IL-1)-induced uveitis with synthetic IL-1 blockers.
Because of the discovery of potent interleukin-1 (IL-1) blocking effects by CK-103A (4,6-dihydropyridazino[4,5-c]pyridazin-5 (1H)-ones) on rat uveitis induced by IL-1, numerous derivatives of CK-103A have been synthesized and their efficacies on the same animal model studied. The uveitis was induced by injection of 1 ng IL-1/10 microliters intravitreally. The inflammation reached peak at 12 hr after the injection of IL-1. The prevention/blockade of IL-1-induced uveitis was measured at this peak inflammation time point. It was found that 8 out of 12 CK-analogs studied produced an effective blockade of IL-1-induced uveitis. Most of them were at least equipotent or even more potent than prednisolone in blocking IL-1-induced uveitis. It is concluded that most dihydropyridazinopyridazin derivatives are effective anti-uveitis compounds. Some could be found to be safe and useful for the treatment of this dreadful disease.
Chiou
G C
GC
Institute of Ocular Pharmacology, Texas A&M University College of Medicine, USA.
Chen
Z
Z
Xuan
B
B
Yamasaki
T
T
Okawara
T
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014605:Uveitis / Q000139:chemically induced*
D000894:Anti-Inflammatory Agents, Non-Steroidal; C091706:CK 103A; D007375:Interleukin-1; D011724:Pyridazines