BFIPRONIL SPRAY (Each ml contains: Fipronil 2.5mg)

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

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.