Synergists can be regarded as chemicals that increase the effect of a pesticide without themselves being toxic. Their mode of action is generally to inhibit the metabolic enzymes (esterases and oxidases) that degrade the insecticide molecules. The ‘gold standard’ synergist is generally regarded as piperonyl butoxide (PBO) a chemical that inhibits both esterases and oxidases.

Historically, PBO was considered a specific inhibitor of P450s, and if synergism was found with PBO the resistance mechanism was (mistakenly) concluded to be an enhanced P450. Now it is known that PBO inhibits both major defence enzyme groups, the sue can be made of another synergist, EN 16-5/1, to correctly diagnose metabolic resistance. This is because EN 16/5 is a specific inhibitor of esterases, having a vastly reduced efficacy against oxidases. The use of EN 16-5/1 together with PBO is known as ‘differential synergism’.

Commonly, PBO was used with natural pyrethrum, but mixing PBO with most classes of insecticide results in an increase in pest mortality. At the simplest level, the enzymes conferring resistance are now having to bind to the synergist as well as the insecticide. However, a superior method is to pre-expose the pest to the synergist before application of insecticide. This concept has been termed ‘temporal synergism’.