What is bioactivation?

Activyl® contains an innovative, highly efficacious agent: indoxacarb. Activyl® is unique because indoxacarb was designed as a pro-insecticide–that requires biological or metabolic activation, also known as “bioactivation”, in susceptible insects to convert it to its highly insecticidal form–thus enhancing its selective toxicity1. In addition, indoxacarb works at a site of action in the flea different from other commercialized insecticides used for flea control1.

The indoxacarb in Activyl® is bioactivated in the flea by enzymatic N-decarbomethoxylation changing it to a more active, highly insecticidal metabolite.

  • Insect esterase enzymes cleave the carbomethoxyl group from the urea linkage
  • Yields an active, highly insecticidal metabolite
  • Pharmacological action in insects
  • Potent and rapid voltage dependent sodium ion channel blocker.2

A unique mode of action

This enzymatic cleavage occurs in insects but not mammals. Mammals metabolize indoxacarb differently, mostly to non-toxic metabolites. In addition, compared to insects, mammalian sodium channels are significantly less sensitive to bioactivated indoxacarb.

Activyl® provides selective toxicity through:

  • High rate of biological activation in susceptible insects
  • Differential sensitivity of sodium ion channels between insects and mammals: significantly lower concentrations are effective in insects3
  • Alternative metabolic pathways (indanone and oxadiazine ring cleavage) in mammals convert indoxacarb mainly to non-toxic metabolites3, 4
  • Relatively minor biological activation in mammals3, 4

Indoxacarb produces its potent effects at a unique binding site in voltage-gated sodium ion channels of the nervous system of susceptible insects.4 This effect differs strikingly from those reported for other insecticides such as pyrethroids, also known to affect the voltage-dependant sodium channels, but at a different site.1, 2, 4

The active metabolite of indoxacarb induces irreversible hyperpolarization of insect nerve cell membranes. It blocks the sodium current amplitude in the neuron differently than the pyrethroids. This results in impaired insect nerve function, feeding cessation, paralysis and death of susceptible insects.

Effective against immature flea stages and thereby breaking
the flea life cycle

Activyl® rapidly affects adult fleas following contact or ingestion resulting first in cessation of flea feeding and then causing flea paralysis and death. Controlled tests show that 90% of adult fleas are killed within 12 hours of application and newly arriving fleas are killed within 8-12 hours for a full month.

Activyl® also kills developing stages of fleas in the environment of treated dogs and cats, meaning that these stages cannot develop into biting adult fleas.
A single treatment with Activyl® inhibits the development of immature fleas exposed to debris from treated animals by more than 90% for at least 4 weeks5. This is reflected in the dramatic decrease in household infestation following treatment with Activyl®.

Since more than just adult fleas are affected, pets get relief and the flea life cycle in the environment is also inhibited, rapidly solving the many stages of your client’s flea problem.

  1. Wing KD, Sacher M, Kagaya Y, Tsurubuchi Y, Mulderig L, Connair M, Schnee M. Crop Protection. 2000;19:537-545.
  2. Lapied B, Grolleau F, Sattelle DB. Br J Pharmacol. 2001;132:587-595.
  3. Zhao X, Ikeda T, Yeh JZ, Narahashi Y. Neurotoxicology 2003;24:83–96.
  4. Dong K. Insect sodium channels and insecticide resistance. InvertNeurosci. 2007;7:17–30.
  5. Data on file, Merck Animal Health.

Activyl® helps break the flea life cycle.

Activyl® is adulticidal, larvicidal and inhibits flea development in the environment.
No Insect Growth Regulator (IGR) required.

Activyl® inhibited 95%-100% of flea development in the
environment of treated pets for at least 35 days post-treatment. 5