Further investigation of anticoccidial activity of 7-bromo-N-(2-imidazolidinylidene)-1H-indazol-6-amine.
The clonidine analog 7-bromo-N-(2-imidazolidinylidene)-1H-indazol-6-amine exhibits potent activity against Eimeria tenella infections in chickens. Disease control was abrogated by a selective alpha 2 antagonist, which is consistent with the dependence of such activity upon binding to receptors with characteristics of the vertebrate alpha 2 adrenoceptor. Lack of significant activity against the parasite in tissue culture and our inability to detect significant binding of alpha 2 adrenergic ligands to E. tenella imply that the anticoccidial action may be an indirect effect mediated by the host. Efficacy varied, depending upon the Eimeria species, being greatest for the cecal species E. tenella and less for the intestinal species. The effects described differ substantially from previous accounts of adrenergic actions on parasitic protozoa. The evidence suggests that we have observed a new mechanism of action for antiparasitic drugs.
Central Research Division, Pfizer Inc., Groton, Connecticut 06340.
A P
AP
Ricketts
J W
JW
McFarland
D M
DM
Newcomb
J A
JA
Olson
J R
JR
Rice
D000316:Adrenergic alpha-Agonists / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001711:Biotransformation / Q000187:drug effects; D002478:Cells, Cultured; D002645:Chickens / Q000469:parasitology*; D003048:Coccidiosis / Q000188:drug therapy / Q000469:parasitology / Q000662:veterinary*; D003049:Coccidiostats / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D003538:Cystamine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016786:Eimeria tenella / Q000187:drug effects*; D007093:Imidazoles / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D007191:Indazoles / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D007422:Intestines / Q000469:parasitology; D008024:Ligands; D011201:Poultry Diseases / Q000188:drug therapy* / Q000469:parasitology; D015016:Yohimbine / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D003049:Coccidiostats; D007093:Imidazoles; D007191:Indazoles; D008024:Ligands; C075038:7-bromo-N-(2-imidazolidinylidene)-1H-indazol-6-amine; D015016:Yohimbine; C029998:benextramine; D003538:Cystamine