Anticoccidial activities of 7-bromo-N-(2-imidazolidinylidene)-1H-indazol-6-amine and other alpha 2 adrenergic agonists.
Activity against the coccidial pathogen Eimeria tenella in chickens has been discovered among alpha 2 adrenergic agonists. The clonidine analog 7-bromo-N-(2-imidazolidinylidene)-1H-indazol-6-amine was active in feed at 7.5 ppm, a concentration similar to the use levels of potent commercial agents, e.g., maduramicin. Additional alpha 2 agonists were also found to have anticoccidial activity, for example, the catecholamine nordefrin, which is chemically unrelated to clonidine. However, alpha 1 agonists and alpha antagonists were inactive. These observations imply that anticoccidial effects reflect involvement of a receptor with the characteristics of the vertebrate alpha 2 adrenoceptor. alpha 2 agonists that permeate the blood-brain barrier (like clonidine) inhibit feed intake at efficacious levels, whereas those that are restricted to the peripheral compartment (such as catecholamines) do not inhibit feed intake as much. Hence, anticoccidial efficacy may be a peripheral adrenergic effect whereas depression of feed intake is likely centrally mediated.
McFarland
J W
JW
Central Research Division, Pfizer Inc., Groton, Connecticut 06340.
Ricketts
A P
AP
Newcomb
D M
DM
Shively
J E
JE
Glazer
E A
EA
D000316:Adrenergic alpha-Agonists / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002645:Chickens / Q000469:parasitology*; D003000:Clonidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D003048:Coccidiosis / Q000188:drug therapy / Q000469:parasitology / Q000662:veterinary*; D003049:Coccidiostats / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D016786:Eimeria tenella; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D007191:Indazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D011201:Poultry Diseases / Q000188:drug therapy* / Q000469:parasitology
D000316:Adrenergic alpha-Agonists; D003049:Coccidiostats; D007093:Imidazoles; D007191:Indazoles; C075038:7-bromo-N-(2-imidazolidinylidene)-1H-indazol-6-amine; D003000:Clonidine