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At least 19 recordsLinked to original sources
PubMed1990

Novel Onchocerca volvulus filaricides from Carapa procera, Polyalthia suaveolens and Pachypodanthium staudtii.

Suitable drugs for the elimination of adult Onchocerca volvulus are still needed since ivermectin, the new microfilaricide, appears to be ineffective against this parasite stage. Herein we report on the identification of filaricides in three medicinal plants. The compounds carapolide A, mexicanolide-methylangolensate mixture from Carapa procera and oliverine from Polyalthia suaveolens or Pachypodanthium staudtii when tested at 10-100 micrograms.ml-1 were found to exhibit considerable microfilaricidal activity after 24 hours of incubation. Oliverine was found to be filaricidal when tested against adult female worms at 100 micrograms.ml-1. Preliminary toxicity studies in mice showed carapolide A and the mexicanolide-methylangolensate mixture to be relatively non-toxic, whereas, oliverine had a minimal lethal dose of 8 mg.Kg-1 of body weight. Based on the above results further pharmacologic studies are recommended to determine, the potential application of the active compounds on the treatment of onchocerciasis.

Animals↗
PubMed1990

Brugia pahangi adults implanted into mice: a possible screen for filaricidal activity.

Brugia pahangi adults grown in the peritoneal cavities of jirds (Meriones unguiculatus) were implanted into the peritoneal cavities of six inbred mouse strains to investigate this system as a screen for detecting filaricidal activity. The mice were given 15 adult B. pahangi and autopsied 35 days later. The recoveries of adult worms were 25%, 35%, 49%, 33%, 26% and 27% of the number implanted respectively for the MF1, TO, NIH, CBA, BALB/c and C3H/HE strains. There was great variation in the number of worms recovered from each strain of mouse. It is concluded that the variation in recoveries was so high that this system is not useful in detecting low level filaricidal activity.

Animals↗
PubMed1987

Filaricidal effect of mefloquine on adults and microfilariae of Brugia patei and Brugia malayi.

Mefloquine, DL-erythro-2,8-bis(trifluoromethyl)-alpha-(2-piperidyl)-4-quinoline methanolhydrochloride, a recently developed antimalarial drug shows filaricidal activity against larval and adult stages of Brugia patei and B. malayi maintained "in vitro". In the concentration range of 10 to 2 microM mefloquine paralysed and killed the filarial worms within 10 h and 3 d, respectively. The lethal effect of mefloquine treatment on larval and adult worms was shown by loss of motility as well as by decrease of lactate excretion by adults. Chloroquine at a concentration of 10 microM did not affect motility and survival of microfilariae and adults of B. patei. Addition of serum to the cultivation medium abolished the filaricidal effect, possibly due to the tight binding of mefloquine to serum proteins, thereby affecting the uptake of the drug into the parasite.

Animals↗
PubMed1978

Evaluation of the intrathoracic injection method for screening of filaricides.

Intrathoracic injection technique was utilized to examine its value in screening of antifilaria drugs in Litomosoides carinii in the cotton rat, Sigmodon hispidus, using existing filaricides such as diethylcarbamazine, Mel W. metrifonate, suramin, arsenics and antimonials. Diethylcarbamazine at a dose of 100 mg/kg for 5 days given intrathoracically caused marked decrease of more than 95% of the microfilaria count in the blood 1 week after the initial injection which is the same effect as was observed by intraperitoneal injection. Whereas adult worms in the pleural cavity were not affected. Mel W at a dose of 10 mg/kg for 5 days killed all adults but had no effect on microfilaria density in the blood. When it was given intraperitoneally, even a larger dose of 50 mg/kg did not affect adults in the pleural cavity. In cotton rats tolerating suramin at 80 and 40 mg/kg for 5 days, adult worms were intact. However, a reduced dose of 20 mg/kg and 10 mg/kg given weekly for 6 weeks showed remarkable macrofilaricidal activity. Thus the slow action of suramin was reproduced by this method. There was no significant change in the microfilaria density in the blood. Aresenics such as Mapharsemin and Neo Neo Arsemin, and antimonials such as stibophen and tartar emetic were shown to have macrofilaricidal activity by intrathoracic injection with no effect on microfilaria density in the blood within a week. Effect of existing filaricides by this method showed remarkable coincidence with their action Wuchereria bancrofti.

Animals↗
PubMed1985

Brugia pahangi in the BALB/C mouse: a model for testing filaricidal compounds.

The BALB/C mouse infected with Brugia pahangi has been evaluated as a model for the selection of filaricidal compounds with activity against immature worms. Mice were infected by the intraperitoneal inoculation of 50 infective larvae and candidate compounds were administered by the intraperitoneal (i.p.), subcutaneous or oral route once daily from day 4 to day 8 post infection. Animals were examined on days 29 to 32 post infection. Variation in the larval recoveries from undrugged mice within and between experimental groups limited the value of drug assessments based upon percentage worm recoveries. The infection rate of undrugged mice was 85% over-all, range 60 to 100%. Using the infection rate of drugged v. undrugged animals as the criterion of activity the test has been evaluated with a series of standard nematicidal compounds. Levamisole and the benzimidazole carbamates, mebendazole, flubendazole and fenbendazole given i.p. at 10 mg/kg daily were active in this screen whilst DEC, DEC-N-oxide, ivermectin, amoscanate, metrifonate and suramin were inactive at the dosages tested. No retardation of growth or morphological abnormalities were observed in worms from the drugged mice.

Animals↗
PubMed1984

Studies of potential filaricides: Part 14--Activity of 1-iso-butoxycarbonyl-4-methylpiperazine against experimental filariasis.

The synthesis and filaricidal activity of 1-iso-butoxycarbonyl-4-methylpiperazine against Litomosoides carinii in Sigmodon hispidus and Dipetalonema viteae in Mastomys natalensis is reported. At an intraperitoneal or oral dose of 3 mg/kg given for 6 days, the compound removed 91% of the circulating microfilariae but had no effect on adult L. carinii. However, it killed all microfilariae and adults of D. viteae at a subcutaneous dose of 50 mg/kg given for 6 days. The compound also possessed chemoprophylactic activity against the larvae of L. carinii and D. viteae at a dose of 30 and 50 mg/kg respectively.

Animals↗
PubMed1994

Activity of albendazole-ivermectin combination and other filaricidal drugs against infective larvae, preadult, microfilariae and adult worms of Molinema dessetae in the rodent Proechimys oris.

The efficacy of albendazole-ivermectin combination was tested an adult and developing stages of Molinema dessetae in the rodent Proechimys oris. Albendazole and ivermectin, both given alone, suramin and diethylcarbamazine were used as reference compounds. The drug combination (albendazole at 10 mg/kg/ day x 5 days and Ivermectin at 0.04 mg/kg/day x 5 days) was effective against infective larvae and preadult worms, and substantially reduced the number of live adult worms. The known filaricidal agents, diethylcarbamazine (400 mg/kg twice daily x 5 days), ivermectin (0.2 mg/kg/day x 5 days), and suramin (40 mg/kg/day x 5 days), as well as albendazole (50 mg/kg/day x 5 days) were active on infective larvae, preadult worms, microfilariae and adult worms. All drugs had the same level of efficacity on infective larvae. Albendazole had the highest efficacy against adult and preadult worms and diethylcarbamazine was the most active on microfilariae. Although the drug combination was not as effective against preadult and adult worms as albendazole alone, the results indicate that albendazole-ivermectin combination at a low dose had prophylactic effect and suggest a possible macrofilaricidal activity.

Administration, Oral↗
PubMed1997

Tissue distribution and metabolism in rat of an ethynesulphonamide with filaricidal activity.

1. The tissue distribution and metabolism of a new filaricidal agent P903 (N-[(2-phenylethynyl)sulfonyl]morpholine) were studied in rat. 2. After s.c. administration of 14C and 13C P903, the Tmax in the blood was observed on day 2. Elimination was slow and > 95% was bound to protein. Radioactivity was distributed in the whole organism but particularly in erythrocytes and the lymphatic channel. Four days later, > 60% of the radioactivity was excreted in urine and faeces at equal amounts and 15% remained at the injection point. 3. In all biological fluids tested no P903 was found but only its metabolites. 4. One principal metabolite, the N-[(2-phenyloxo-2-ethane) sulphonyl] morpholine or oxosulphonamide was identified in blood, urine and faeces as compared with the reference compound by GC/MS and NMR. This latter molecule was detected following hydrolysis by hydrochloric acid but not with beta glucuronidase/sulphatase. 5. Unconjugated and conjugated oxosulphonamide represented > 85% of the radioactivity at all times tested in blood but only 38 and 35% respectively of urinary and faecal radioactivity on day 1 after the administration of the labelled drug. 6. Thus, P903 is rapidly converted to a reactive metabolite, probably an oxirene, which is then conjugated with endogenous components to form conjugated oxosulphonamide and an unknown metabolite. The role of this reactive metabolite in antifilarial activity seems to be very important in understanding the mechanism of action of P903.

Animals↗
PubMed1989

In-vitro evaluation of filaricidal activity of GABA and 1,3-dipalmitoyl-2-(4-aminobutyryl)glycerol HCl: a diglyceride prodrug.

A diglyceride ester of gamma-aminobutyric acid (GABA) has been synthesized and its filaricidal activity compared with GABA, and progabide in-vitro, on infective larvae and microfilariae of Molinema dessetae, a rodent filaria. GABA induced paralysis in infective larvae but was inactive on microfilariae. There were interactions between the culture medium and GABA. The ester drug at 0.1 mmol L-1 (1,3-dipalmitoyl-2-(4-aminobutyryl)glycerol HCl) was as active as progabide on infective larvae and hundredfold more potent than GABA. Its microfilaricidal activity at 1 mmol L-1 was lower than that progabide at 0.1 mmol L-1 but a delayed effect was observed. The data confirm filariae sensitivity to GABA derivatives.

Animals↗
PubMed1990

[The research of filaricides for the control of african onchocerciasis].

Amongst several other chemical series, the epoxi and ethylenesulfonamides (which are more stable) have been selected after that we have shown good filaricidal activities on the Filaria Molinema dessetae. This has been confirmed on other models. Good activity was observed with O. gutturosa adult male in vitro, while microfilariae of O. lienalis were insusceptible to the selected compounds. The future of these products was discussed, in the prospect of their development and in relation with their mode of action and the other available pharmacological data.

Drug Evaluation, Preclinical↗
PubMedDate not supplied

[Use of surviving infectious larvae of Dipetalonema dessetae in study and research on filaricidal substances].

Dipetalonema dessetae in Proechimys oris, the natural final host is a rodent filariasis model used as an in vivo antifilarial screening test. The laboratory vector is Aedes aegypti. Infective larvae L3 isolated from the intermediate host develop and remain healthy for up to 30 days in a biphasic culture medium composed of a cell feeder layer (L 929) and RPMI 1640 supplemented with foetal calf serum. This culture technique has enabled us to screen antifilarial compounds on a new in vitro test. This model has been tested to several pharmacological classes of anthelmintics and effective concentrations 90% are given: diethylcarbamazine 430 mg/l, suramin 490 mg/l, Mel W 3.5 mg/l, mebendazole 78 mg/l, flubendazole 45 mg/l, levamisole 0.55 mg/l, morantel 0.62 mg/l, ivermectin 1.2 mg/l, amoscanate 2.3 mg/l. In vitro test response is remarkable for neurotoxic anthelmintics and nitro-compounds. Furthermore, all compounds considered as reference filaricides are active. For each compound, the in vitro and in vivo results have been compared to appreciate usefulness as well as limits of this in vitro test.

Animals↗
PubMed1971

Chemotherapeutic studies on Litomosoides carinii infection of Mastomys natalensis. 1. The filaricidal action of 2,6-bis-benzimidazoles.

The antifilarial action of 2-[2-(4-hydroxyphenyl)-6-benzimidazolyl]-6-(1-methyl-4-piperazyl) benzimidazole (HOE 33258) was investigated in Mastomys natalensis infected with Litomosoides carinii. The subcutaneous administration of HOE 33258 in a single daily dose for 5 consecutive days, or at other intervals, produced, depending on the dosage, a rapid reduction in the number of microfilariae in the circulating blood. The reduction amounted to more than 90% within 7-14 days after the treatment was started or at the end of the dosage schedule. The small, slow increase in the microfilarial count during a period of 6-7 weeks after treatment ended reached not more than half the number present before treatment. HOE 33258 showed marked activity on the reproductive system of mature female worms, although only few macrofilariae were killed by the drug. The results also demonstrated the usefulness of L. carinii infection of M. natalensis as a model for the evaluation of the filaricidal activity of drugs.

Animals↗
PubMed1978

Chemotherapeutic studies on Litomosoides carinii infection of Mastomys natalensis. 7. Filaricidal activity of furazolidone.

Investigations were carried out on the filaricidal activity of furazolidone against Litomosoides carinii infection in Mastomys natalensis. Oral administration of the drug in daily doses of 25, 50, 75, and 150 mg/kg body weight on 5 consecutive days revealed respectively 96,4, 99,3 and, with the two later doses, 100% reduction of macrofilariae in the pleural cavities, and produced a continuing dose-dependant decrease of microfilaraemia in the circulating blood. After oral doses of 5 x 50 mg/kg, all the adult parasites were killed within two weeks of the start of treatment and were found encapsulated in fibrinous masses in the pleural cavities. Deformed and degenerated embryonic stages could be seen in female worms as early as 3 days after the end of treatment. Furazolidone possesses a considerable chemotherapeutic index.

Administration, Oral↗
PubMed1976

[Preliminary results of the use of a new rodent filaria, Dipetalonema dessetae (Bain, 1973), in the evaluation of filaricides].

The sensitivity of this filarial worm living in his natural host has been identified with respect to 2 well known filaricidal compounds. With diethylcarbamazine the microfilaremia drops rapidly but not completely and a long term treatment destroys the adults. Suramin is toxic to the adults and to the microfilariae. This experimental model is therefore more sensitive than anything presently available.

Animals↗
PubMed1997

[Experimental studies of filaricides].

Several chemical compounds have shown filarical activities, which are presented and compared in this presentation: diethylcarbamazin, ivermectin, benzimidazoles and original compounds as epoxy and ethynesulphonamide, or carboxamides. Their metabolism and tissue distribution are depending of the host, and whether hosts are parasitized or not. Reference compounds have filaricidal activities depending of the stage of Filaria, and of the experimental model. The necessity of a good model is essential to extrapolate the results. Biochemical targets which can be identified from these animals models may be inappropriate for use in human filariasis; that is why fundamental research is still necessary in this area.

Animals↗
PubMed1993

Experimental chemotherapy of filariasis: comparative evaluation of the efficacy of filaricidal compounds in Mastomys coucha infected with Litomosoides carinii, Acanthocheilonema viteae, Brugia malayi and B. pahangi.

Eleven types/classes of compound with antifilarial activity were comparatively evaluated in Mastomys coucha infected with Litomosoides carinii, Acanthocheilonema viteae, Brugia malayi or B. pahangi. The paper deals with the efficacy of (i) predominantly microfilaricidal compounds [diethylcarbamazine, levamisole, avermectins (ivermectin, milbemycin), nitrofurans (nitrofurantoin, hydroxymethylnitrofurantoin, nifurtimox, furazolidone, furapyrimidone), organophosphorals (metrifonate, haloxon), and aminophenyl-amidines], (ii) predominantly macrofilaricidal compounds [suramin, benzimidazoles (flubendazole, mebendazole, oxfendazole, ciclobendazole, albendazole, cambendazole, fenbendazole), and arsenicals (thiacetarsamide, Mel PH, R7/45)], and (iii) micro- and macrofilaricidal compounds [benzazole derivatives (CGP 20376 and other benzothiazoles) and nitrophenylamines (amoscanate, CGP 6140)]. Minimum effective doses against microfilariae and minimum curative doses against adult filariae as well as detailed data on dose-efficacy relationships are reported for the various drugs. The results obtained in M. coucha are compared with those published for other experimental in vivo filarial systems, thus attempting to describe a general status of in vivo antifilarial activity of the compounds.

Animals↗