Haemonchus contortus: ivermectin-induced paralysis of the pharynx.
How the avermectins cause the elimination of gastrointestinal nematodes from host animals has not yet been clearly identified. Using visual and radiometric parameters to measure oral ingestion in Haemonchus contortus, we showed that ivermectin (IVM) rapidly inhibited ingestion at concentrations > or = 10(-10) M. Motility, monitored quantitatively with an automated motility meter, was unaffected by IVM at concentrations < or = 10(-8) M, while ATP levels were unaffected at concentrations < or = 10(-6) M. Since motility and ATP levels, independent measures of short-term viability, are unaffected by concentrations of IVM that effectively block oral ingestion, the drug can be used as a chemical ligature. Although H. contortus was shown to be dependent upon an exogenous supply of glucose for survival in culture, IVM (10(-9) and 10(-7) M) altered neither the uptake of 3-O-[3H]methylglucose nor the metabolism of [13C]glucose by the parasite. These data suggest that H. contortus depends upon the transcuticular uptake of glucose in culture. If oral ingestion of other nutrients is essential for long-term survival in vivo, disruption of this process may represent the primary mechanism of IVM action.
Geary
T G
TG
Animal Health Therapeutics Research, Upjohn Company, Kalamazoo, Michigan 49001.
Sims
S M
SM
Thomas
E M
EM
Vanover
L
L
Davis
J P
JP
Winterrowd
C A
CA
Klein
R D
RD
Ho
N F
NF
Thompson
D P
DP
D019325:3-O-Methylglucose; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000378:metabolism; D006189:Haemonchus / Q000187:drug effects* / Q000502:physiology; D007559:Ivermectin / Q000494:pharmacology*; D008757:Methylglucosides / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009068:Movement / Q000187:drug effects; D010614:Pharynx / Q000187:drug effects / Q000502:physiology
D008757:Methylglucosides; D019325:3-O-Methylglucose; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D007559:Ivermectin; D000255:Adenosine Triphosphate; D005947:Glucose