Editing Pyrethroid (section)

==Mode of action==
Pyrethroids are [[excitotoxin|excitotoxic]] to [[axon]]s. They act by preventing the closure of the [[voltage-gated sodium channel]]s in the axonal [[membrane]]s. The sodium channel is a [[membrane protein]] with a [[hydrophilic]] interior. This interior is shaped precisely to allow [[sodium ion#aqueous solutions|sodium ions]] to pass through the membrane, enter the axon, and propagate an [[action potential]]. When the toxin keeps the channels in their open state, the nerves cannot [[repolarization|repolarize]], leaving the axonal membrane permanently [[depolarization|depolarized]], thereby paralyzing the organism.<ref name=Soderlund>{{cite journal |doi=10.1016/s0300-483x(01)00569-8 |pmid=11812616 |title=Mechanisms of pyrethroid neurotoxicity: Implications for cumulative risk assessment |journal=[[Toxicology (journal)|Toxicology]]|volume=171 |issue=1 |pages=3–59 |year=2002 |last1=Soderlund |first1=David M |last2=Clark |first2=John M |last3=Sheets |first3=Larry P |last4=Mullin |first4=Linda S |last5=Piccirillo |first5=Vincent J |last6=Sargent |first6=Dana |last7=Stevens |first7=James T |last8=Weiner |first8=Myra L |bibcode=2002Toxgy.171....3S }}</ref> Pyrethroids can be combined with the synergist [[piperonyl butoxide]], a known [[enzyme inhibitor|inhibitor]] of [[microsomal P450]] enzymes which are important in metabolizing the pyrethroid. By that means, the efficacy (lethality) of the pyrethroid is increased.<ref name=Denholm>{{cite journal |doi=10.1017/S0007485300054262 |title=An unconventional use of piperonyl butoxide for managing the cotton whitefly, ''Bemisia tabaci'' (Hemiptera: Aleyrodidae) |journal=[[Bulletin of Entomological Research]] |volume=88 |issue=6 |pages=601–10 |year=2009 |last1=Devine |first1=G.J |last2=Denholm |first2=I }}</ref> It is likely that there are other mechanisms of intoxication also.<ref name="Soderlund-Bloomquist-1989" /> Disruption of [[neuroendocrine cell|neuroendocrine]] activity is thought to contribute to their irreversible effects on insects, which indicates a pyrethroid action on [[voltage-gated calcium channel]]s (and perhaps other [[voltage-gated ion channel|voltage-gated channels]] more widely).<ref name="Soderlund-Bloomquist-1989" />