7.1.2. Model synergists
Model synergists are chemical tools that are useful for determining the biological basis of synergistic interactions. Model synergists are not overtly toxic to bees at the doses used, but can greatly alter the toxicity of other agents by changing the absorption, disposition, metabolism or excretion of the second agent.
Commonly used inhibitors of detoxicative metabolism include piperonyl butoxide (PBO), which inhibits cytochrome P450 monooxygenase enzyme activity, S,S,S-tributylphosphorotrithioate (DEF), which inhibits carboxylesterase activity and diethyl maleate (DEM), which inhibits glutathione S-transferase activity. These inhibitors are applied topically to the thoracic notum at sublethal doses of 10 µg (PBO and DEF) or 100 µg (DEM) dissolved in 1 µl of acetone 1h prior to treatment with a second chemical agent (Iwasa et al., 2004; Johnson et al., 2006).
The membrane-bound Multi Drug Resistance transporter can be inhibited by feeding bees verapamil at a concentration of 1mM dissolved in 50% sucrose syrup (Hawthorne and Dively, 2011).