tribendimidine and Necatoriasis

The antinematode effect of tribendimidine (TBD) and its metabolites has been studied. A total of 107 hamsters were each infected with 250 Necator americanus third stage infective larvae (NaL3) for 25 days. In the first test, 75 hamsters were divided equally into 15 groups for determination of ED(50) and ED(90.) Among them, five groups were treated orally with TBD or its metabolite, p-(1-dimethylamino ethylimino)aniline (aminoamidine, deacylated amidantel, BAY d 9216, dADT), at single doses of 1, 2, 4, 8, and 16 mg/kg. The remaining five groups were administered with acetylated dADT (AdADT) at single oral doses of 8, 12, 18, 24, and 30 mg/kg. In the second test, 20 hamsters were equally divided into four groups. Two groups were treated intramuscularly with TBD and dADT at a single dose of 16 mg/kg, while in the remaining two groups, single intramuscular dose of AdADT 15 or 30 mg/kg was administered. In the third test, two groups of six hamsters were treated orally with terephthalaldehyde (TPAL) and terephthalic acid (TPAC) at a single dose of 1,000 mg/kg. Other 85 rats, each infected with 300 Nippostrongylus braziliensis third stage infective larvae (NbL3), were used in three tests. For determination of ED(50) and ED(90) in the first test, five groups of five rats were treated orally with TBD or dADT at single doses of 3.0, 4.2, 5.9, 8.2, and 11.5 mg/kg or 2.0, 2.9, 4.2, 6.1, and 8.8 mg/kg, respectively. In the second test, three groups of eight to nine rats were treated orally with TBD at a single 8.4-mg/kg dose (ED(90)) and AdADT 100 or 200 mg/kg, respectively. In the third test, two groups of four rats were treated orally with TPAL and TPAC at a single dose of 1,000 mg/kg. Twenty-four to 48 h post-treatment, all the feces of each hamster and rat were collected for recovery of worms expelled from the feces. Following this period, all of the animals were sacrificed, and the adult hookworm or N. braziliensis from small intestine and large intestine were recovered and counted for calculation of worm burden reduction. The results showed that the ED(50) and ED(90) for TBD, dADT, and AdADT determined in treatment of N. americanus-infected hamsters were 1.849 and 13.598, 3.922 and 54.354, as well as 20.966 and 51.633 mg/kg, respectively. In intramuscular administration of TBD and dADT at single dose of 16 mg/kg or AdADT 30 mg/kg, similar worm burden reductions of 71.4-76.3% were observed. Two other metabolites, i.e., TPAL and TPAC, exhibited no effect against N

Topics: Administration, Oral; Animals; Anthelmintics; Cricetinae; Disease Models, Animal; Feces; Injections, Intramuscular; Intestine, Large; Intestine, Small; Mesocricetus; Necator americanus; Necatoriasis; Nippostrongylus; Phenylenediamines; Rats; Treatment Outcome

Laboratory golden hamsters (Mesocricetus auratus) were infected with Necator americanus under several different parasite and host conditions to optimize the model for testing anthelminthic drugs. The results confirmed that male hamsters were more susceptible to infection than females. Host age in the range of 5-15 weeks was not a factor that impacted on adult worm burden, and similar worm burdens were achieved using doses of 150, 250 or 500 N. americanus L3 (NaL3). The largest numbers of adult hookworms were recovered on days 21-28 post-infection, with a significant decrease at days 40-50 post-infection. Therefore adult worm recovery is maximal approximately 11-18 days prior to patency and host blood loss. From these studies a drug evaluation protocol was developed using 150 NaL3 as the infectious dose and then evaluating the anthelminthic effects of the drugs albendazole, tribendimidine, and pyrantel pamoate on days 21-28 post-infection. The model confirms the anthelminthic activity of albendazole, tribendimidine, and pyrantel pamoate and has the potential as a laboratory animal model to detect emerging drug resistance.

Topics: Age Factors; Albendazole; Animals; Anthelmintics; Cricetinae; Disease Models, Animal; Erythrocyte Count; Female; Male; Mesocricetus; Necator americanus; Necatoriasis; Phenylenediamines; Pyrantel Pamoate; Sex Factors

Golden hamsters infected with Necator americanus were treated orally with a new anthilmintic tribendimidin (N, N'-[bis-4'-(1-dimethyl amino ethylidene amino)phenyl] 1,4-phenyene dimethylidyne amine) at a single dose of 150 mg/kg. One h after medication, some worms showed cuticular swelling, fusion of transverse striations and attachment of host leucocytes onto the worm's damaged cuticular surface. Four h post treatment, the cuticle revealed a moderate swelling or even erosion. Meanwhile, the ventral cutting plates appeared to be swollen. After 8-24 h, severe cuticular swelling, erosion and peeling in female worm tails and male copulatory bursa were seen. No increases in lesions in the small intestinal mucosa of infected golden hamsters were observed 4-8 h after medication.

Topics: Animals; Anthelmintics; Cricetinae; Female; Intestinal Diseases, Parasitic; Intestinal Mucosa; Male; Mesocricetus; Microscopy, Electron, Scanning; Necator; Necatoriasis; Phenylenediamines

Topics: Ancylostomiasis; Animals; Anthelmintics; Cricetinae; Dogs; Necatoriasis; Nematode Infections; Nippostrongylus; Phenylenediamines; Pyrantel Pamoate; Rats