QUICFIP PLUS SPRAY

Indications

• Control of fleas in dogs and cats
• Control of ticks in dogs
• Control of ants and cockroaches in agricultural settings

Dosage

Children: Fipronil is not generally recommended for use in children. Consult the BNF for Children for specific guidance.

Adults: Dosage varies based on the specific formulation and species being treated. Refer to product labeling for precise dosing information.

Mechanism of action

Fipronil acts as a GABA-gated chloride channel antagonist. It blocks the chloride channels associated with the gamma-amino butyric acid (GABA) receptors in mammals and the GABA and glutamate receptors in insects. This blockage disrupts the neurotransmission processes, resulting in hyperexcitation and eventually death of the insect.

Pharmacodynamics

Fipronil exhibits high potency against a range of insect pests through its mechanism of action, which leads to increased neuronal activity and, ultimately, paralysis in target insects. In mammals, its selective action on insect GABA receptors and relative safety is attributed to the differences in receptor structure and function, limiting its adverse effects in non-target organisms.

Pharmacokinetics

Fipronil is absorbed through oral, dermal, and inhalation routes, with distribution to various tissues. Its metabolism occurs primarily in the liver, where it is converted to several metabolites, some of which retain insecticidal activity. The elimination half-life can vary significantly based on the route of exposure and the species in question. The compound is known to persist in the environment, which can lead to bioaccumulation in certain ecosystems.

Pregnancy

Fipronil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Fipronil is not recommended during breastfeeding due to the lack of data on its safety in nursing infants.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Topical solution
• Spot-on solution
• Oral formulation

Indications

• Insect growth regulation
• Pest control in agricultural settings
• Larvicidal treatment in water bodies

Dosage

Children: Refer to specific guidelines or literature for paediatric dosing, as this may vary based on application and formulation.

Adults: Refer to specific guidelines or literature for adult dosing, as this may vary based on application and formulation.

Mechanism of action

Methoprene functions as an insect juvenile hormone agonist, blocking metamorphosis in certain insect species. It has been shown that a metabolite, methoprene acid, activates vertebrate retinoid X receptors (RXRs) and may interfere with retinoic acid-regulated developmental processes. Research indicates that methoxy-methoprene acid acts as a ligand for RXRs and can activate transcription through retinoic acid receptor/RXR response elements, although methoprene itself and its breakdown products do not activate transcription in specific cell lines.

Pharmacodynamics

Methoprene's pharmacodynamics involve its role in mimicking juvenile hormones, which are crucial for maintaining larval and pupal stages in insects. By acting as an analogue, methoprene prevents the normal progression to adult stages, thus inhibiting reproduction and population growth. The ability of methoprene acid to influence RXR pathways suggests potential effects on vertebrate developmental processes, although the clinical significance of this interaction remains to be fully elucidated.

Pharmacokinetics

The pharmacokinetics of methoprene involve its absorption, distribution, metabolism, and excretion in target organisms. Methoprene is lipophilic, allowing for significant absorption through lipid membranes. It is metabolized into methoprene acid and other breakdown products, which may exert additional biological effects. The specifics of its half-life and excretion pathways in humans or animals are not well-defined in available literature.

Pregnancy

There are no adequate and well-controlled studies of methoprene in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether methoprene is excreted in human milk. Caution should be exercised when methoprene is administered to a nursing woman.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Insect growth regulators (IGRs) for pest control

Mechanism of action

Fipronil is a second-generation phenilpirazol insecticide that is used in agriculture and veterinary medicine for protection against fleas, ticks, ants, cockroaches and other pests. The insecticide blocks the chloride channels associated with the gamma-amino butyric acid (GABA) receptors in mammals and the chloride channels associated with the GABA and glutamate (Glu) receptors in insects. GABA-gated chloride channel antagonists. MicroRNAs (miRNAs), which are a class of small noncoding RNAs, can modulate the expression of many protein-coding genes when an organism is exposed to an environmental chemical. We previously demonstrated that miR-155 was significantly downregulated in adult zebrafish (Danio rerio) in response to fipronil (5-amino-1-[2,6-dichloro-4-(trifluoromethyl) phenyl]-4-[(trifluoromethyl) sulphinyl]-1H-pyrazole-3-carbonitrile) exposure. However, the regulation of this miRNA's predicted target gene cyb561d2, which is a member of the cytochrome b561 (cyt b561) family involved in electron transfer, cell defence, and chemical stress, has not been experimentally validated to date. In this study, we evaluated the effects of fipronil on miR-155 and cyb561d2 in zebrafish. The expression of miR-155 was downregulated, whereas cyb561d2 was upregulated in both mRNA and protein level in a dose-dependent manner upon stimulation of fipronil. The dual luciferase report assay demonstrated that miR-155 interacted with cyb561d2 3'-untranslated regions (3'-UTR). The expression of cyb561d2 was reduced in both mRNA and protein levels when ZF4 cells were transfected with an miR-155 mimic, whereas its expression levels of both mRNA and protein were increased when endogenous miR-155 was inhibited by transfection with an miR-155 inhibitor. The results improved our understanding of molecular mechanism of toxicity upon fipronil exposure, and presents miR-155 as a potential novel toxicological biomarker for chemical exposure. Fipronil is the first phenylpyrazole insecticide widely used in controlling pests, including pyrethroid, organophosphate and carbamate insecticides. It is generally accepted that fipronil elicits neurotoxicity via interactions with GABA and glutamate receptors, although alternative mechanisms have recently been proposed. This study evaluates the genotoxicity of fipronil and its likely mode of action in Drosophila S2 cells, as an in vitro model. Fipronil administrated the concentration- and time-dependent S2 cell proliferation. Intracellular biochemical assays showed that fipronil-induced S2 cell apoptosis coincided with a decrease in the mitochondrial membrane potential and an increase reactive oxygen species generation, a significant decrease of Bcl-2 and DIAP1, and a marked augmentation of Cyt c and caspase-3. Because caspase-3 is the major executioner caspase downstream of caspase-9 in Drosophila, enzyme activity assays were used to determine the activities of caspase-3 and caspase-9. Our results indicated that fipronil effectively induced apoptosis in Drosophila S2 cells through caspase-dependent mitochondrial pathways. For more Mechanism of Action (Complete) data for Fipronil (7 total), please visit the HSDB record page.

Mechanism of action

Methoprene (isopropyl (2E,4E)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate) is an insect juvenile hormone agonist that blocks metamorphosis in some insects. Recent evidence suggests that a metabolite, methoprene acid, activates vertebrate retinoid X receptors (RXRs), and may interfere with retinoic acid-regulated developmental processes. Methoprene, methoxy-methoprene acid, and two major breakdown products were tested for their ability to interfere with retinoid-regulated pathways when using transfected cells. The CV-1 cells were transiently transfected with genes encoding RXRs and response elements attached to luciferase reporters, and retinoic acid-sensitive F9 cells were stably transfected with retinoic acid receptor (RAR)/RXR response elements attached a lacZ reporter (Sil-REM/beta-gal-NEO). Experiments confirmed that methoxy-methopreneacid acted as a ligand for RXRs and was capable of activating transcription through RAR/RXR response elements. However, neither methoprenenor the breakdown products, 7-methoxycitronellal and 7-methoxycitronellic acid, activated transcription in transfected CV-1 or F9 cells.Methoprene and methoxy-methoprene acid may interfere with the conversion of all-trans-retinol and all-trans-retinaldehyde to all-trans-retinoic acid in the F9-derived cell line. Methoprene was as effective as the retinol dehydrogenase inhibitor citral in blocking the retinol-induced transcription of RAR/RXR-regulated reporter genes, whereas methoxy-methoprene acid blocked transcription stimulated by retinaldehyde. In holometabolous insects such as mosquito, Aedes aegypti, midgut undergoes remodeling during metamorphosis. Insect metamorphosis is regulated by several hormones including juvenile hormone (JH) and 20-hydroxyecdysone (20E). The cellular and molecular events that occur during midgut remodeling were investigated by studying nuclear stained whole mounts and cross-sections of midguts and by monitoring the mRNA levels of genes involved in 20E action in methoprene-treated and untreated Ae. aegypti. We used JH analog, methoprene, to mimic JH action. In Ae. aegypti larvae, the programmed cell death (PCD) of larval midgut cells and the proliferation and differentiation of imaginal cells were initiated at about 36 hr after ecdysis to the 4th instar larval stage (AEFL) and were completed by 12 hr after ecdysis to the pupal stage (AEPS). In methoprene-treated larvae, the proliferation and differentiation of imaginal cells was initiated at 36h AEFL, but the PCD was initiated only after ecdysis to the pupal stage. However, the terminal events that occur for completion of PCD during pupal stage were blocked. As a result, the pupae developed from methoprene-treated larvae contained two midgut epithelial layers until they died during the pupal stage. Quantitative PCR analyses showed that methoprene affected midgut remodeling by modulating the expression of ecdysone receptor B, ultraspiracle A, broad complex, E93, ftz-f1, dronc and drice, the genes that are shown to play key roles in 20E action and PCD. Thus, JH analog, methoprene acts on Ae. aegypti by interfering with the expression of genes involved in 20E action resulting in a block in midgut remodeling and death during pupal stage. ... Here, a major malaria vector, Anopheles gambiae Giles, was used as a model insect to study the action of methoprene on female reproduction. Ecdysteroid titers and expression profiles of ecdysone-regulated genes were determined before and after a blood meal. An ecdysteroid peak was detected at 12 hr post blood meal (PBM). The maximum expression of ecdysone-regulated genes, such as ecdysone receptor (EcR), hormone receptor 3 (HR3) and vitellogenin (Vg) gene, coincided with the ecdysteroid peak. Interestingly, topical application of methoprene at 6 hr PBM delayed ovarian development and egg maturation by suppressing the expression of ecdysone-regulated genes in female mosquitoes. The data suggest that ecdysteroid titers are correlated with Vg s