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At least 37 records · Page 2Linked to original sources
PubMed1994

Pregnancy alterations following xenobiotic-induced delays in ovulation in the female rat.

Chlordimeform [N'-(4-chloro-o-tolyl)-N,N-dimethylformamidine] has been shown to cause a 1-day delay in the surge of luteinizing hormone (LH) in ovariectomized, steroid-primed female rats, presumably through its ability to block CNS alpha-noradrenergic receptors and consequently CNS regulation of anterior pituitary function. In the present study, we determined whether a chlordimeform-induced delay in the ovulatory surge of LH would alter pregnancy outcome in intact females. Chlordimeform (50 mg/kg) or sodium pentobarbital (35 mg/kg), as a positive control, was administered in order to delay ovulation 24 (1-day delay) or 48 hr (2-day delay). Females were then housed with proven fertile males on the evening of proestrus (0-day delay group), the following evening (1-day delay group), or the evening after that (2-day delay group). The number of receptive females in each group, the mean lordosis quotient, and the number of sperm-positive females in each group were recorded. All females were killed on Gestation Day 20. The number of pregnant females in the 1- or 2-day delay groups was reduced with both chlordimeform and pentobarbital. Also, delaying ovulation for 1 or 2 days with either compound resulted in a significant reduction in the number of live pups present on Gestation Day 20 and a decrease in the number of implantation sites. Litter size was not affected if the females were mated on the same day that treatment was administered (0-day delay).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Influence of the formamidine pesticide chlordimeform on ovulation in the female hamster: dissociable shifts in the luteinizing hormone surge and oocyte release.

The formamidine pesticide chlordimeform (CDF) has been found to interfere with the hormonal control of ovulation in the rat by a presumptive disruption in the catecholaminergic regulation of the midcycle surge of luteinizing hormone (LH). While the brain hypothalamic mechanisms underlying generation of the hamster surge have not been as well-defined, there is evidence for an adrenergic component. The present experiments were designed to investigate the effects of CDF on ovulation in the golden hamster and whether any observed alterations are associated with differences in the appearance of the surge. Intraperitoneal CDF injections (0, 75, 150, or 200 mg/kg) at 1400 hr on proestrus caused a dose-related reduction in oocytes retrieved at 0700 hr on the day of estrus. Additional experiments demonstrated that this effect was due to a delay in ovulation and not a decrease in the complement of oocytes released. Doses of 150 or 200 mg/kg at 1100 hr or 200 mg/kg at 1600 hr were without a comparable ovulatory effect. Characterization of the LH surge indicated that there was a dose-related delay, but that this effect was not sufficient to account for the delay in ovulation. Animals dosed at 1100 hr (150 or 200 mg/kg) exhibited shifts in the surge identical to those animals injected at 1400 hr, but did not show any such detectable effects on the time of oocyte release. CDF administered at 1100 or 1400 hr also caused alterations in serum estradiol and progesterone, even at a relatively low dose of 37.5 mg/kg. The results indicate that CDF given at a time just prior to the preovulatory rise in LH is able to impede ovulation in the hamster by possibly influencing some ovulatory event(s) triggered by the surge. Also, the ability of CDF to alter the timing of LH release is consistent with catecholaminergic participation in the generation of the gonadotropin signal stimulating the final events leading to ovulation. Under the present conditions, this perturbation can be characterized as a delay in the LH trigger, rather than a blockade.

Animals↗
PubMed2001

Interaction of formamidine pesticides with the presynaptic alpha(2)-adrenoceptor regulating.

The effects of the formamidine pesticides amitraz and chlordimeform on the alpha(2)-adrenergic receptor subtype that mediates the release of [(3)H]noradrenaline by synaptosomes from rat hypothalami were studied. We initially characterized the presynaptic autoreceptor on noradrenergic nerve endings using selective antagonists. Yohimbine (a nonselective alpha(2) antagonist) and BRL 44408 (selective for subtypes alpha(2A)/alpha(2D)) diminished the inhibitory effect of xylazine on K(+)-evoked release of [(3)H]noradrenaline; the K(B) values were 481 and 154 nM, respectively. In contrast, prazosin (a selective alpha(2B)/alpha(2C) antagonist) did not modify the inhibitory effect of xylazine. These results indicate that the release of noradrenaline by noradrenergic nerve endings in the rat hypothalamus is regulated by alpha(2D)-adrenoceptors, a species variation of the human alpha(2A) subtype. We then assessed the effects of the two pesticides on the K(+)-evoked release of [(3)H]noradrenaline. Amitraz reduced release in a dose-dependent manner; the effect observed at the maximal concentration tested (10 microM) was 13.0 +/- 2.0% and it was reversed by yohimbine. Amitraz also diminished the inhibitory effects of the alpha(2)-adrenergic agonists clonidine and xylazine. Chlordimeform displayed no effects, possibly because the true active compound of this insecticide is its demethylated metabolite. Based on these findings we conclude that the formamidine pesticides act as partial agonists of presynaptic alpha(2D)-adrenergic receptors in the rat hypothalamus. This interaction may be responsible for the in vivo alterations in catecholaminergic regulation of cyclic variations in gonadotropin-releasing hormone (GnRH) secretion, which can have grave functional repercussions on the reproductive system of mammals exposed to these xenobiotics.

Adrenergic alpha-Agonists↗
PubMed1979

Effects of pesticides on the reticuloendothelial system.

The information available concerning the effects of compounds utilized as pesticides on functions of the reticuloendothelial system is quite limited. Review of selected examples of such studies in this and other reports (3) reveals considerable diversity in terms of species of experimental animal, purity and dose of pesticide, length of exposure, and class of pesticide employed. Observations include depression, enhancement, or no significant effect on the selected reticuloendothelial system function studies. With the present available information it is difficult to formulate general conclusions or to predict whether or not any individual pesticide will consistently and significantly alter any specific function of the reticuloendothelial system. At the present time, it is not known if pesticides within a single chemical class act in a similar manner in regard to their ability to influence reticuloendothelial system function. In addition, the relationship, if any, between the toxic, mutagenic teratogenic, or carcinogenic potential of any pesticide and its ability to alter the reticuloendothelial system is also unknown. More extensive systematic studies in experimental animal models would appear to be required before protocols to effectively evaluate the potential of pesticides to influence reticuloendothelial system function in man can be developed.

Animals↗
PubMed1987

Interaction of the pesticide chlordimeform with adrenergic receptors in mouse brain: an in vitro study.

Chlordimeform (N'(4-chloro-o-tolyl)-N, N-dimethylformamidine; CDM) is a formamidine insecticide acaricide whose major active metabolite is its N-monomethyl analog, desmethylchlordimeform, (DCDM). While their pesticidal action in invertebrates appears to be related to activation of octopamine receptors, their mechanism of action in mammals has not been established. Because of similarities between octopamine and adrenergic receptors and suggestions of CDM and DCDM action on adrenoceptors, the in vitro interactions of CDM and DCDM with adrenoceptors were studied. In mouse brain membrane preparations CDM inhibited the binding of [3H]-clonidine to alpha 2- adrenoceptors and of [3H]-WB4101 to alpha 1-adrenoceptors with IC50 values of 18.2 and 87 microM, respectively. DCDM was a much more potent inhibitor, with IC50 values toward alpha 2-, and alpha 1-adrenoceptors of 44 nM and 1 microM, respectively. Both compounds were only weak inhibitors of the binding of [3H]-dihydroalprenolol to beta-adrenoceptors and of [3H]-quinuclidinyl benzilate to muscarinic receptors and were inactive toward benzodiazepines and gamma aminobutyric acid (GABAA) receptors. Inhibition of [3H]-clonidine binding by both compounds was competitive, as indicated by a decreased receptor affinity without changes in receptor density. Interaction of CDM and DCDM with [3H]-WB4101 binding, on the other hand, was more complex, and not of the competitive type. These results show that CDM and its metabolite DCDM can interact directly in vitro with alpha-adrenergic receptors, suggesting that these receptors could mediate some of the effects of CDM and DCDM in vivo.

Amidines↗
PubMed1978

Increased feeding in rats treated with chlordimeform and related formamidines: a new class of appetite stimulants.

Low doses of the formamidine pesticide, chlordimeform (CDM) induce voracious daytime feeding in non-food deprived rats. Following CDM (10 mg/kg), food intakes were five times control intakes after 3 h and 1.1 times control intakes after 24 h. Other selected formamidines, such as the N-demethylated metabolite of CDM, and amitraz, increased 3-h food intake by two and five times control intake, respectively. Anorexia accompanied by excessive CNS stimulation was noted with higher doses of CDM (above 40 mg/kg) and other formamidines. This contrasts with the sedation usually observed with high doses of other structurally diverse appetite stimulants. In addition, hyperphagia was not observed with other CNS stimulants or local anesthetics such as amphetamine, cocaine, and holocaine. Thus the formamidines constitute a new class of appetite stimulants, which should prove to be useful agents for the study of feeding behavior.

Amidines↗
PubMed1989

Enhanced susceptibility to kindling by chlordimeform may be mediated by a local anesthetic action.

The formamidine pesticides amitraz and chlordimeform have recently been shown to be potent proconvulsants (Gilbert 1988). Two main neuroactive properties have been identified as mediators of formamidine neurotoxicity, alpha-2 adrenergic agonism and local anesthetic actions. These two proposed mechanisms of formamidine action were contrasted using electrical kindling of the amygdala. Male rats were administered 0, 10 and 40 mg/kg of the local anesthetic lidocaine, 0, 0.01 and 0.10 mg/kg of the alpha-2 adrenergic agonist clonidine or 0, 10 and 30 mg/kg chlordimeform, IP, once per day. After each injection, kindling stimulation was delivered through chronically-implanted electrodes. The high dosage of chlordimeform and both dosages of lidocaine enhanced the rate of kindling development (mean sessions to stage 5 seizures = 8.6 +/- 1.16, 10.15 +/- 1.04 and 8.5 +/- 0.95, respectively) relative to controls (mean = 14.59 +/- 1.36). Afterdischarge (AD) durations were increased over the first seven sessions by both treatments, but the total cumulative AD did not differ from controls. Clonidine, by contrast, delayed kindling development (mean 27.57 +/- 1.97) and shortened the mean AD duration over the first seven sessions. These data provide support for a local anesthetic action of chlordimeform and stand in contrast to several recent demonstrations of alpha-2 activity of formamidines as a primary contributor to formamidine toxicity.

Amidines↗
PubMed1981

Inhibition of monoamine oxidase activity after combined action of chlordimeform with the antidepressant nialamide.

The 40-day oral administration of 5, 10, and 50 mg/kg chlordimeform to male rats moderately decreased monoamine oxidase activity (MAO) in the brain, liver, and serum, determined with the substrates kynuramine, tyramine, tryptamine, serotonin, dopamine, and benzylamine. The enzyme was inhibited predominantly in the liver. The study of MAO inhibition after 10 days application of 2, 6, 10, 15, and 20 mg/kg nialamide revealed that 2 mg/kg had a threshold effect. A dose of 6 mg/kg resulted in a pronounced decrease in the enzyme activity. Experiments with a 30-day application of 5, 10 and 50 mg/kg chlordimeform were made, followed by treatment with 6 mg/kg nialamide in combination for another 10 days. The statistical evaluation by the Student's t-test demonstrated increased MAO inhibitory action. Dose-effect relationship was established with kynuramine in liver, brain, and serum, and with benzylamine in liver.

Amidines↗
PubMed1976

Uptake and persistence of pesticides in cultured human cells.

The uptake and persistence of 14C-labeled pesticides in cultur-s of human embryonic lung diploid cells were studied. Chlordimeform, DDT, parathion, aldrin and dieldrin were selected as test compounds. Results obtained from these experiments divided the chemical into two groups. The first group consisted of three chemical DDT, aldrin and dieldrin which are generally classified as persistent insecticides while the second group was composed of chlordimeform and parathion, generally considered to be non-persistent insecticides. The rate of initial cellular incorporation of first group was approximately 20 to 70 times greater than the non-persistent insecticides. During the course of an incubation, the amounts of pesticide taken up by the cells decreased gradually.

Aldrin↗
PubMed1977

MAO inhibition, an unlikely mode of action for chlordimeform.

Inhibition constants of several formamidines, their corresponding formanilides and other representatives of compounds derived from aniline, such as phenylureas, N-phenyl-carbamates and acylanilides, were determined for rat liver monoamine oxidase. The reversability of the inhibition and the lack of correlation between inhibition potencies and toxicities of the compounds tested add to the opinion that MAO inhibition is not a prominent factor in chlordimeform poisoning.

Amidines↗
PubMed1979

[Enzymatic N-acetylation of tryptamine by brain homogenates of Locusta migratoria before and after intoxication by chlordimeform or lindane (author's transl)].

Brain homogenates of Locusta migratoria are found to possess enzyme capable of catalyzing the N-acetylation of tryptamine. A main product of the enzymatic reaction is isolated and identified as N-acetyltryptamine by chromatography analyse. Both insecticides, chlordimeform and lindane, inhibit enzyme activity. A direct correlation between the degree of intoxication and acetylation of tryptamine is described.

Acetylation↗
PubMed1980

Pharmacological modulation of edema mediated by prostaglandin, serotonin and histamine.

Previous studies demonstrated that the formamidine pesticide chlordimeform (CDM) reversibly inhibited prostaglandin biosynthesis and prevented the late (PG-mediated) phase of carrageenin-induced hind paw edema. This study emphasizes antagonism by CDM of the early (5HT and histamine-mediated) phase of carrageenin edema. CDM and cyproheptadine both antagonized paw edema induced by albumin (5HT and histamine-mediated) and by the direct injection of 5HT and histamine, whereas aspirin and the PG antagonist, SC-19220, were ineffective. As expected, cyproheptadine selectively reduced the early phase, whereas aspirin and SC-19220 selectively reduced the late phase of carrageenin-induced edema. These results are thus consistent with earlier studies demonstrating PG mediation of the late phase of carrageenin edema, and 5HT and histamine mediation of albumin edema and the early phase of carrageenin edema. In addition, they indicate that CDM possesses multiple acute anti-inflammatory actions not exhibited by aspirin, by SC-19220 or by cyproheptadine alone.

Albumins↗