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PubMed1981

Resistance to benzimidazole anthelmintics in equine strongyles. 2. Evidence of side-resistance, and susceptibility of benzimidazole-resistant strongyles to non-benzimidazole compounds.

The susceptibility of a known thiabendazole-resistant population of small strongyles to anthelmintics of both benzimidazole and non-benzimidazole groups, was determined. In the first study, 42 horses infected with thiabendazole-resistant small strongyles were allocated to 6 groups. Treatment groups received one of the following anthelmintics: mebendazole, febantel, febantel plus trichlorphon, morantel tartrate, or a combination of thiabendazole, piperazine and trichlorphon. Morantel tartrate and the thiabendazole/piperazine/trichlorphon combination produced highly significant (p less than 0.001) reductions in faecal strongyle egg counts 20 days post-treatment. Mebendazole, febantel and febantel plus trichlorphon failed to reduce strongyle egg counts significantly. Larval culture and differentiation indicated that in all cases of anthelmintic failure, small strongyles of the sub-family Cyathostominae were involved. Eighteen horses from groups in which treatment had failed were re-allocated to 3 groups. Treatment with either morantel tartrate or haloxon was highly efficient in reducing faecal strongyle egg counts. In the final study, fifty-four horses, infected with benzimidazole-resistant small strongyles were allocated to 10 groups. On day zero, each treatment group received one of the following anthelmintics: thiabendazole, cambendazole, mebendazole, oxibendazole, piperazine, thiabendazole/piperazine, cambendazole/piperazine, mebendazole/piperazine or oxibendazole/piperazine. Oxibendazole, piperazine and the benzimidazole/piperazine combinations produced highly significant reductions in faecal strongyle egg counts 20 days post-treatment (p less than 0.001). When administered alone, benzimidazole anthelmintics failed to reduce strongyle egg counts significantly, with the exception of oxibendazole. Larval culture and differentiation indicated that in all cases of anthelmintic failure, the species involved were small strongyles of subfamily Cyathostominae. There was no significant increase in benzimidazole resistance level (based on in vitro assay) as a result of drug treatment, over one generation.

Animals↗
PubMed1997

5-hydroxytryptamine1A receptor-mediated increases in receptor expression and activation of nuclear factor-kappaB in transfected Chinese hamster ovary cells.

The regulation in expression of human 5-hydroxytryptamine1A (5-HT1A) receptors by agonists and antagonists was studied in a stable transfected Chinese hamster ovary cell line expressing the human 5-HT1A receptor. Receptor density and affinity were measured with [125I]4-(2'-methoxyphenyl)-1-[2'-[N-(2'-pyridinyl)-p-iodobenzamido ]ethyl]piperazine ([125I]p-MPPI), a selective antagonist of 5-HT1A receptors. Treatment of Chinese hamster ovary cells with serotonin or the selective agonist (+/-)-8-hydroxy-N,N-dipropyl-2-aminotetralin stimulated a 2.5-fold increase in receptor density. The antagonists 4-(2'-methoxyphenyl)-1-[2'-[N-(2'-pyridinyl)-p-iodobenzamidoethyl] piperazine, (-)-(S)-pindolol, and spiperone also stimulated up-regulation of receptor expression. Agonist- and antagonist-stimulated up-regulations of receptor expression were mechanistically different. The effect of agonists was inhibited by pertussis toxin, actinomycin D, and cycloheximide. Antagonist-stimulated up-regulation was inhibited by cycloheximide, only partially inhibited by actinomycin D, and not inhibited by pertussis toxin. In the course of identifying potential pathways for coupling of the receptor to activation of transcription, we demonstrated that agonists activate the transcription regulatory factor nuclear factor-kappaB (NF-kappaB). Agonists were found to stimulate degradation of the inhibitory subunit, IkappaB alpha, and to increase the activity of a NF-kappaB-dependent CAT reporter gene. In contrast, the antagonist 4-(2'-methoxyphenyl)-1-[2'-[N-(2'-pyridinyl)-p-iodobenzamidoethyl] piperazine neither elicited degradation of Ikappa-B alpha nor increased reporter activity. Our data suggest that expression of 5-HT1A receptors can be regulated by both agonists and antagonists and that the agonist but not antagonist stimulation occurs concomitantly with activation of NF-kappaB.

Animals↗
PubMed2000

Synthesis of new 2-(aminomethyl)-4-phenylpyrrolo[1,2-a]-quinoxalines and their preliminary in-vivo central dopamine antagonist activity evaluation in mice.

In the search for antipsychotic agents that are not associated with extrapyramidal side effects, efforts have been focused on finding selective D4-receptor antagonists and investigating their pharmacology. Our laboratory has developed a synthesis program for new pyrroloquinoxalines with therapeutic potential. We have described the synthesis of some new pyrroloquinoxalines with substituted arylpiperazino or aryltetrahydropyrido chain at position 3 of the quinoxaline ring (2-(4-phenylpiperazin-1-ylmethyl)-4-phenylpyrrolo[1,2-a]quinoxalinium oxalate (3a), 2-[4-(2-methoxyphenyl)piperazin-1-ylmethyl]-4-phenylpyrrolo[1,2-a]quinoxalinium oxalate (3b), 2-[4-(3-trifluoromethylphenyl)piperazin-1-ylmethyl]-4-phenylpyrrolo[1,2-a]quinoxalinium oxalate (3c), 2-[4-(4-chlorophenyl)piperazin-1-ylmethyl]-4-phenylpyrrolo[1,2-a]quinoxalinium oxalate (3d), 2-(4-pyridin-2-ylpiperazin-1-ylmethyl)-4-phenylpyrrolo[1,2-a]quinoxalinium oxalate (3e), and 2-(4-phenyl1,2,3,6-tetrahydropyridin-1-ylmethyl)-4-phenylpyrrolo[1,2-a]quinoxalinium oxalate (3f)). A preliminary pharmacological study of these products was conducted using climbing behaviour induced by apomorphine (2.5 mg kg(-1), s.c.) in mice. The derivatives were administered intraperitoneally 30 min before apomorphine. Haloperidol, chlorpromazine and clozapine were used as references. Among this series, 3b, 3c and 3f revealed a central dopamine antagonist activity. The most active derivative was 3b, which exhibited a profile relatively close to clozapine.

Animals↗
PubMed1996

Oxidative metabolism of flunarizine and cinnarizine by microsomes from B-lymphoblastoid cell lines expressing human cytochrome P450 enzymes.

The oxidative metabolism of cinnarizine [(E)-1-(diphenylmethyl)-4-(3-phenyl-2-propyl)piperazine, CZ] and flunarizine [(E)-1-[bis(4-fluorophenyl)methyl]-4-(3-phenyl-2-propyl)piperazine, FZ] was examined in microsomes from lymphoblastoid cells that expressed human cytochrome P450 (CYP) enzymes. Among 10 kinds of CYP enzymes examined, only CYP2D6 catalyzed p-hydroxylation of the cinnamyl phenyl ring of CZ (C-2 formation) and FZ (F-2 formation), and only CYP2B6 exhibited activity for p-hydroxylation (C-4 formation) of the diphenylmethyl group of CZ at a substrate concentration of 50 microM. On the other hand, CYP2C9 together with CYP1A1, -1A2 and/or -2A6 mediated N-desalkylation at the 1- and 4-positions of the piperazine ring of the two drugs that formed C-1 and C-3 from CZ and F-1 and F-3 from FZ, respectively, whereas CYP2C8, -2C19, -2E1 or -3A4 did not show detectable activity for these reactions under the conditions used. We then examined kinetics for the oxidative metabolism of CZ and FZ using CYP2B6 and -2D6 that have considerable activities. CYP2D6 with Km values of 2 to 4 microM had intrinsic clearance values (Vmax/Km) of 0.31 and 0.14 ml/min/nmol CYP for C-2 and F-2 formation, respectively, while CYP2B6 with a Km value of 17 microM exhibited the clearance value of 0.10 ml/min/nmol CYP for C-4 formation. These results suggest that CYP2D6 mainly mediates p-hydroxylation of the cinnamyl phenyl rings of CZ and FZ, and CYP2B6 mediates that of the diphenylmethyl group of CZ.

B-Lymphocytes↗
PubMed2002

Synthesis of N-substituted piperazinyl carbamoyl and acetyl derivatives of tetrahydropapaverine: potent antispasmodic agents.

The synthesis and structure-activity-relationship (SAR) for a series of N-substituted piperazinyl carbamoyl 7-15 and piperazinyl acetyl 18-26 derivatives of tetrahydropapaverine have been carried out. The general synthetic methods of carbamoyl tetrahydropapaverine analogues involve N-substituted piperazines and carbamoyl imidazole tetrahydropapaverine as starting materials. Another route for synthesizing these compounds, involving the formation of carbamoyl imidazole piperazine has also been explored. Acylation of tetrahydropapaverine followed by substitution with various piperazinyl moities afforded the acetyl tetrahydropapaverine derivatives. Variously substituted piperazines have been used to monitor the effect of electron releasing and electron withdrawing substituents upon the antispasmodic activity of the molecules. Effect of varying electron densities on the antispasmodic activity, by altering the position of these groups on the benzene ring has also been monitored. Pharmacological methods involve the in vitro antispasmodic activity studies on a freshly removed guinea pig ileum using a force displacement transducer amplifier connected to a physiograph. Among the analogues synthesized in the present study, a promising compound 7, a potent muscle relaxant as compared to papaverine has been obtained.

Animals↗
PubMed1992

Comparative metabolism of flunarizine in rats, dogs and man: an in vitro study with subcellular liver fractions and isolated hepatocytes.

1. The biotransformation of 3H-flunarizine ((E)-1-[bis(4-fluorophenyl)methyl]-4-(3-phenyl-2-propenyl)piperazine dihydrochloride, FLUN) was studied in subcellular liver fractions (microsomes and 12,000 g fraction) and in suspensions or primary cell cultures of isolated hepatocytes of rats, dogs and man. The major in vitro metabolites were characterized by h.p.l.c. co-chromatography and/or by mass spectrometric analysis. 2. The kinetics of FLUN metabolism was studied in microsomes of dog and man. The metabolism followed linear Michaelis-Menten kinetics over the concentration range 0.1-20 microM FLUN. 3. A striking sex difference was observed for the in vitro metabolism of FLUN in rat. In male rats, oxidative N-dealkylation at one of the piperazine nitrogens, resulting in bis(4-fluorophenyl) methanol, was a major metabolic pathway, whereas aromatic hydroxylation at the phenyl of the cinnamyl moiety, resulting in hydroxy-FLUN, was a major metabolic pathway in female rats. In incubates with hepatocytes, these two metabolites were converted to the corresponding glucuronides. 4. In human subcellular fractions, aromatic hydroxylation to hydroxy-FLUN was the major metabolic pathway. In primary cell cultures of human hepatocytes, oxidative N-dealkylation at the 1- and 4-piperazine nitrogen and glucuronidation of bis(4-fluorophenyl)methanol were observed. The in vitro metabolism of FLUN in humans, resembled more than in female rats and in dogs than that in male rats. 5. The present in vitro results are compared with data of previous in vivo studies in rats and dogs. The use of subcellular fractions and/or isolated hepatocytes for the study of species differences in the biotransformation of xenobiotics is discussed.

Animals↗
PubMed1981

Morphological Observation Of Enterobius Vermicularis Expelled By Various Anthelmintics.

When enterobiasis cases were treated with anthelmintics only for one time, the interval to recurrence was variable by different drugs used. And this phenomenon is supposedly connected with biological or developmental cycle of the worm and the consequent efficacy of the different anthelmintics. This study was undertaken to confirm this fact by studying the expelled worms morphologically to correlate the anthelmintics efficacy and stage of worm development in Enterobius vermicularis. A total of 131 children in 3 orphanages was examined by 4 anal swabs (mean positive rate, 80%). They were randomized into 5 experimental groups. Each group was treated with placebo, mebendazole, pyrantel, pyrvinium, and piperazine (70 mg/kg, single dose) respectively. After treatment, all stool were collected for 3 days to get the expelled Enterobius. A total of 6,165 pinworms was studied under the microscope. The sex was discriminated and the length was individually measured. A number of male pinworms was collected in all groups. Females of 2~11 mm in length were also collected in 5 groups. However, significantly larger number of short females was observed in mebendazole group compared with other groups. Twenty-one days after the first treatment, all children were again treated with mebendazole. Once more stool were examined. A total of 1,853 worms was collected. In mebendazole group, there were no females longer than 8.74 mm in the second treatment. In pyrvinium group, 8.31mm in lenght was the longest for female. However in control, pyrantel and piperazine groups, females of 2~11 mm in length were collected. From above results, one could conclude that the removing ability of mebendazole and pyrvinium was satisfactory for the worms in the early stage of development in Enterobius. Pyrantel and single dose of piperazine showed less effective in worm reduction ability especially on those at the early stages.

Journal Article↗
PubMedDate not supplied

[Effect of trihexphenidyl on the excitability of alpha motor neurons of the foot plantar flexor in chemically induced parkinsoniam rigidity].

For assessment of the effect of trihexiphenidil on the excitability state of the alpha-motoneurons of the plantar flexor of the foot in patients with drug-induced parkinsonian rigidity curves of the excitability of motoneurons of the soleus muscle were plotted in two variants of experiments: I. with afferent stimulation of the Ia fibres of the soleus muscle as the conditioning and testing stimulus (tibial nerve in the popliteal fossa), II. with afferent stimulation of Ia fibres of the anterior tibial muscle (peroneal nerve behind the fibular capitulum) used as the conditioning stimulus and stimulation of the tibial nerve as the testing stimulus. These investigations were carried out on 12 psychiatric patients who received no drugs at the time of these investigations (control group), 13 similar patients treated with chlorpromazine, 12 treated with phenothiazine compounds with piperazine ring in the side chain. The investigations were repeated 30-50 min. after oral administration of trihexiphenidil 5 mg. In variant I typical excitability curves were obtained and 5 phases could be discerned in them. In patients treated with piperazine-containing phenothiazine derivatives inducting more significant parkinsonian effects phase III - depression - was significantly shortened, and the excitability was raised in phase IV. In variant II phases III and IV were reversed and in phase IV a rise in excitability was observed in place of depression. In variant II in the group of drug-induced parkinsonism as compared with controls the rise in exictability was greater in phase III and depression in phase IV was smaller. The effect of trihexiphenidil in variant I depended on the initial state. In controls and in patients treated with chlorpromazine trihexiphenidil reduced the duration of phase III of depression and decreased its intensity. In atients treated with phenothiazines containing the piperazine ring depression in phase III was weak but increased after trihexiphenidil administration and increased excitability in phase IV was decreased. The curves became similar to those obtained in controls. In variant II in the control group excitability in phase III increased after trihexiphenidil administration.

Administration, Oral↗
PubMedDate not supplied

Tissue metabolites of trifluorperazine, fluphenazine, prochlorperazine, and perphenazine. Kinetics in chronic treatment.

Repeated oral treatment of male rats with piperazine-substituted phenothiazine drugs in doses of 25 mg/kg or more daily led to an accumulation of metabolites containing an ethylenediamine group instead of the piperazine ring. These products of ring degradation with and without removal of the N-alkyl group were found, together with the parent drugs and their N-dealkylated metabolites, in liver, lung, kidney, and spleen, as well as in brain when high doses were administered. After termination of treatment, the ethylenediamine derivatives were eliminated more slowly than were their congeners containing the intact piperazine ring. Parallel observations were made in dogs given fluphenazine in daily doses of up to 40 mg/kg. Quantitative differences were observed in the relative amounts of mono- and disubstituted ethylenediamine metabolites accumulated in rat tissues during treatment with the various drugs; the proportion of the monosubstituted product formed by N-dealkylation and ring cleavage declined in the following order: perazine, prochlorperazine, trifluoperazine, fluphenazine, perphenazine. Condensation products of the ethylenediamine derivatives with formaldehyde were split in the extraction procedure used.

Animals↗
PubMed1988

The relaxation induced by indole and nonindole 5-HT agonists in the molluscan smooth muscle.

1. The abilities of two indole agonists and some nonindole agonists to induce relaxation of catch contraction and the influence of the agonists on cyclic AMP (cAMP) levels in the anterior byssus retractor muscle (ABRM) of Mytilus were investigated. 2. 5-MeOT (5-methoxytryptamine) and 5-MeODMT (5-methoxy-N,N-dimethyltryptamine) dose-dependently relaxed the contraction. 3. TFMPP (m-trifluoromethylphenyl piperazine), PAPP (p-amino-phenyl TFMPP) and mCPP (1-(3-chlorophenyl)piperazine dose-dependently relaxed the contraction, but 2MPP (1-(2-methylphenyl) piperazine and quipazine did not. 4. 5-MeOT (10(-6)M), 5-MeODMT (10(-6)M), TFMPP (10(-4)M), 2MPP (10(-4)M), quipazine (10(-4)M) and 8-OH-DPAT (3 x 10(-5) M) significantly reduced the cAMP levels, but PAPP (3 x 10(-4)M) and mCPP (10(-4)M) did not have any effect on cAMP levels. 5. These findings indicate that the pharmacological properties of 5-HT1-like receptors in the ABRM are similar to those of 5-HT1A receptors in mammalian tissues, and that the changes in cAMP levels induced by the agonists used are unlikely to be directly linked to the relaxation induced by them.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1987

Tissue-dependent alpha adrenoceptor activity of buspirone and related compounds.

The present organ chamber and receptor binding studies were designed to evaluate the alpha adrenoceptor subtype (alpha-1 vs. alpha-2) and tissue selectivity of buspirone and the related compounds, gepirone, isapirone and 1-(2-pyrimidinyl)-piperazine (a metabolite of buspirone). Buspirone, gepirone and isapirone were found to possess weak alpha-1 adrenoceptor affinity (relative to prazosin) but significant and selective alpha-1 adrenoceptor intrinsic efficacy (relative to norepinephrine, phenylephrine and ST-587), which was expressed in a tissue- and species-dependent manner. The rank order for alpha-1 adrenoceptor affinity (isapirone greater than buspirone approximately equal to gepirone) was different from the rank order for alpha-1 adrenoceptor intrinsic efficacy (buspirone greater than gepirone greater than isapirone). The tissues that were the most responsive to norepinephrine and ST-587 (i.e., rat and rabbit aorta) were the same tissues in which the intrinsic efficacy of buspirone was expressed. In contrast, 1-(2-pyrimidinyl)-piperazine was inactive at alpha-1 adrenoceptors. Although no alpha-2 adrenoceptor intrinsic efficacy was observed for any of the compounds, isapirone and 1-(2-pyrimidinyl)-piperazine displayed weak alpha-2 adrenoceptor affinity (relative to rauwolscine). Recent studies have shown buspirone to have an effect on central and peripheral monoaminergic mechanisms. The demonstration in the present study that buspirone and related compounds display significant alpha adrenoceptor activity suggests that alpha adrenoceptor involvement should be considered as a potential contributing factor in the central nervous system and/or peripheral activity of this class of compounds.

Animals↗
PubMed1981

Apparent inactivity of several antiparasitic compounds against the eyeworm Thelazia lacrymalis in equids.

Activity of 15 compounds, given alone or in mixtures [butamisole, cambendazole, caviphos, febantel (alone or with trichlorfon), fenbendazole, ivermectin, levamisole-piperazine, oxfendazole, oxibendazole, pyrantel pamoate (alone or with piperazine-carbon disulfide complex), thiabendazole (alone or with piperazine or with trichlorfon), tioxidazole, and trichlorfon], against Thelazia lacrymalis was evaluated in 102 equids. Determination of activity was based on comparison of infection rate in treated animals examined at necropsy with infection rate of dead equids in our contemporary surveys. None of the compounds appeared to be active against T lacrymalis.

Animals↗
PubMed1996

Novel benzodioxan derivative, 5-[3-[((2S)-1,4-benzodioxan-2-ylmethyl) amino]propoxy]-1,3-benzodioxole HCl (MKC-242), with anxiolytic-like and antidepressant-like effects in animal models.

Behavioral effects of MKC-242 (5-{3-[((2>)-1,4-benzodioxan-2-ylmethyl)amino] propoxy}-1,3-benzodioxole CHl), a novel and selective serotonin 1A receptor agonist, were investigated in rats and mice and compared against those of diazepam, buspirone and tandospirone. MKC-242 (0.0625-0.25 mg/kg, p.o.) significantly increased punished drinking in water-deprived rats. The reference compounds also increased punished drinking at doses of 10 to 40 mg/kg, p.o. The increase by MKC-242 was blocked by N-tert-butyl-3-(4-(2-methoxypenyl)piperazin-1-yl) -2-phenylpropanamide, a serotonin 1A receptor antagonist. MKC-242 (0.1-0.5 mg/kg, p.o.) also increased social interaction under high light and unfamiliar conditions in rats. It had weak benzodiazepine-like side effects in mice. MKC-242 (1, 3 mg/kg, p.o.) attenuated the reduction of locomotion caused by restraint stress in rats, the same effects were observed on both buspirone (100 mg/kg, p.o.) and tandospirone (100 mg/kg, p.o.). In the forced swimming test in rats, MKC-242 (0.3-3 mg/kg, i.p.), 8-hydroxy-2-(di-n-propylamino) tetralin (1, 3 mg/kg, i.p.) and amitriptyline (30 mg/kg, i.p.) reduced immobility, although diazepam, buspirone and tandospirone did not. The reduction by MKC-242 and 8-OH-DPAT was antagonized by N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-1-yl) -2-phenylpropanamide. Moreover, the reduction was also blocked by 1-(2--pyrimidinyl)piperazine (1-PP), a common metabolite of buspirone and tandospirone. These findings suggest that MKC-242 possesses potent anxiolytic and antidepressant properties that are mediated via an activation of serotonin 1A receptors.

Animals↗
PubMed1977

The effect of niclosamide on Echinococcus granulosus, Taenia hydatigena and Taenia ovis infections in dogs.

The effect of niclosamide (particle size 1 micron m) and its piperazine salt (particle size 5-10 micron m) on Echinococcus granulosus and Taenia hydatigena has been investigated. The piperazine salt of niclosamide was also tested for activity against Taenia ovis. These trials involved 326 dogs. Irrespective of particle size, the drug was found to be virtually inactive against 28-day-old E granulosus. Some evidence was found indicating that there may be a low degree of activity against 70-day-old worms. The drug was found to be effective at 32 mg/kg and 64 mg/kg against T hydatigena and 50 mg/kg against T ovis. Some evidence was obtained that milk decrease the efficiency of the piperazine salt against T hydatigena at the lower dose rates. Micronisation of the drug did not increase the efficiency against this parasite. Vomiting and diarrhoea were common sequelae.

Administration, Oral↗
PubMed2005

Chiral separation and CD characterisation of enantiomeric cyclotriphosphazene derivatives.

The gem-disubstituted cyclotriphosphazene 1 reacted with piperazine (pip) to give the piperazine-bridged derivative 2, which is expected to exist in meso and racemic forms because the two PCl (pip) groups are stereogenic. The proton-decoupled (31)P NMR spectrum of 2 gave rise to two similar sets of ABX signals in a 1:1 ratio, consistent with formation of diastereoisomers. The meso and racemic forms of compound 2 were separated by column chromatography on silica gel and characterised by elemental analysis, mass spectrometry, (31)P NMR spectroscopy, and X-ray crystallography. Using HPLC with a chiral stationary phase, the racemic form of compound 2 was further separated into enantiomers, which were characterised by circular dichroism (CD) spectroscopy. This is the first report of the separation of enantiomers in the field of cyclophosphazene chemistry and hence the first CD spectra of derivatives in which the cyclophosphazene ring is at the chiral centre.

Chromatography, High Pressure Liquid↗
PubMed1989

Mutagenicity of urine from mice exposed orally to nitrite and various aminated antiparasitic drugs.

Mutagenic N-nitroso compound formation from the in vitro reaction of amebicides and anthelmintic drugs, which are pyrimidine derivatives or contain secondary aliphatic amines or heterocyclic nitrogens, has been previously described (Arriaga Alba et al.: Environmental and Molecular Mutagenesis 12:65-73, 1988). Under similar conditions, antiparasitic drugs containing halogenated derivatives of tertiary amines or quaternary ammonium salts do not form mutagenic nitrosated compounds. In the present study the mutagenic activity of mouse urine was determined after oral administration of sodium nitrite and the two above-mentioned groups of drugs (pyrantel pamoate, chloroquine, piperazine and dehydroemetine/iodochlorhydroxyquin and bephenium hydroxynaphthoate, respectively). Results show that the simultaneous administration of piperazine or chloroquine with sodium nitrite produced urinary mutagens that appeared conjugated as glucuronides, whereas pyrantel pamoate and dehydroemetine in the presence of nitrite caused only slightly mutagenic urine. No mutagenic activity was detected in the urine of mice to which halogenated derivatives of tertiary amines (iodochlorhydroxyquin) or quaternary ammonium salts (bephenium hydroxynaphthoate) were administered together with nitrite.

Amebicides↗
PubMed1986

Effects of diethylcarbamazine on the motility of Angiostrongylus cantonensis and Dirofilaria immitis.

Effects of piperazine derivatives, especially of diethylcarbamazine (DEC) on adult Angiostrongylus cantonensis and Dirofilaria immitis were examined. Piperazine (3 X 10(-5)-10(-4) M) paralyzed A. cantonensis and the action was antagonized by picrotoxin. 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) (10(-5)-10(-4) M) caused contraction but little effect was produced by strychnine. An inhibitory effect on untreated preparations was caused by lower concentrations (3 X 10(-6)-10(-5) M) of diethylcarbamazine citrate (DEC) and also on the preparations contracted by eserine. A stimulatory effect was also seen when higher concentrations (10(-4)-3 X 10(-4) M) of this drug were applied to both preparations. The inhibitory action of DEC was antagonized by gabergic antagonists such as picrotoxin and bicuculline, but not by alpha-adrenergic antagonists like dibenamine and phentolamine. When the worm preparation was paralyzed by strychnine or hexylresorcinol (inhibitors of the release of acetylcholine in this worm), the stimulatory effect of DEC was blocked, but pyrantel (a nicotinic cholinergic agonist) contracted the paralyzed preparation. However, the effect of DEC on D. immitis (10(-7)-3 X 10(-4) M) was inhibitory, and this action was also antagonized by picrotoxin. These results suggest that the DEC inhibitory and stimulatory action is through the gabergic and cholinergic mechanisms in adult A. cantonensis and D. immitis.

Angiostrongylus↗
PubMed1987

A comparison of the genetic activity of pyrvinium pamoate with that of several other anthelmintic drugs in Saccharomyces cerevisiae.

Several anthelmintic drugs that are used routinely in oxyuriasis therapy were analyzed for genotoxicity in a diploid mitotic recombination and gene conversion assay (strain D5 of Saccharomyces cerevisiae), and in a haploid yeast reversion assay (strain XV185-14C). Piperazine citrate, piperazine adipate, mebendazole and thiabendazole did not appear to be genotoxic in either yeast strain. Pyrvinium pamoate induced the reversion of the missense, nonsense and frameshift alleles in strain XV185-14C, whereas pyrantel pamoate induced only the reversion of the frameshift allele. Pyrvinium pamoate was recombinogenic in strain D5, and there is an indication that pyrantel pamoate, at the lowest dose that was tested, might induce gene conversion or aneuploidy.

Anthelmintics↗