Advances in non-peptide glucagon receptor antagonists.
This review deals with glucagon receptor antagonism as a possible treatm ent of Type 2 diabetes. The role of glucagon in animal models has been studied by glucagon antibodies as model antagonists. Depending upon the animal model studied, selective glucagon deficiency produced by immunone utralisation suggests that glucagon plays a modest (rats) to substantial (rabbits) role in the maintenance of euglycaemia and is an important dia betogenic factor. These data strongly suggest that glucagon antagonism may be a beneficial and safe therapeutic approach for the treatment of T ype 2 diabetes. Further, the progress on non-peptide glucagon receptor antagonists is reviewed with special focus on the different classes of g lucagon receptor antagonists published, namely quinoxalines /pyrrolo[1,2 -a]quinoxalines, mercaptobenzimidazoles, 2-pyridyl-3,5-diarylpyrroles, q uinoline hydrazones, 4-phenylpyridines, and alkylidene hydrazides.
Madsen
P
P
Departments of Medicinal Chemistry, Novo Nordisk A/S, Novo Nordisk Park, Maaloev, DK-2760 Maaloev, Denmark. pem@novo.dk
Brand
C L
CL
Holst
J J
JJ
Knudsen
B
B
D000818:Animals; D000906:Antibodies / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors*
D000906:Antibodies; D007004:Hypoglycemic Agents; D010455:Peptides; D018027:Receptors, Glucagon