Glutamate-gated chloride channel
Ivermectin binds with high affinity to glutamate-gated chloride channels
which occur in invertebrate nerve and muscle cells, causing an increase in
the permeability of the cell membrane to chloride ions with hyperpolarization
of the nerve or muscle cell. Hyperpolarization results in paralsysis and death
of the parasite either directly or by causing the worms to starve. (Consult
2005) At least one study, however, seems to suggest a depolarizing rather
than hyperpolarizing role for Ivermectin on the glutamate-gated chloride channel.
(Pemberton, Franks et al. 2001) However, in either case, the end result is
the deactivation of the channel by manipulation of chloride levels.
Figure 1. A schematic of the unactivated and activated.
Binding of glutamate (or ivermectin) causes the glutamate gated channel to
open thereby permitting entry of chloride ions, which induce hyperpolarization.
Source: http://www.bioanim.com/CellTissueHumanBody6/O3channels/kanalGlutam1lgwa.html
Selectivity
Selective activity of compounds of this class is attributable to the facts
that some mammals do not have glutamate-gated chloride channels and that avermectins
have low affinity for mammalian ligand-gated chloride channels. In addition,
ivermectin does not readily cross the blood-brain barrier in humans but rather
targets its antiparasitic activity to the general circulation.
Figure 2 The blood barrier is created by the tight apposition
of endothelial cells lining blood vessels in the brain preventing easy passage
of large macromolecules and pathogens between the circulation and the brain.
Ivermectin cannot penetrate this barrier.
Source: http://www-ermm.cbcu.cam.ac.uk/03006264h.htm
Targetted organisms
The target of Ivermectin is largely aimed at the microfilaria stage of various
parasites. Ivermectin is active against various life-cycle stages of many
but not all nematodes. It is active against tissue microfilariae of Onchocerca
volvulus. Its activity against Strongyloides stercoralis is limited to the
intestinal stages. (Consult 2005)
The macrofilaricdal effect of Ivermectin is debatable but there is evidence
for the macrofilaricidal effect of Ivermectin in Onchocerca volvulus. 3-monthly
regimen appeared to cause increase adult female worm death due to a direct,
anthelminthic, macrofilaricdal action of ivermectin or by increasing the prevalence
and intensity of a potentially fatal pleomorphic ovarians neoplasm (PN)(Duke
2005)
There is also evidence in nematode studies particularly those in Trichinella
spiralis that ivermectin may work by blocking signal transmission from interneurons
to excitatory motoneurons that that GABA is the neurotransmitter being blocked.
(Moreno)
a. 
b. 
c. 
Figure 3 Ivermectin is effective at paralyzing and killing the microfilaria of various parasites including Onchocerca volvulus (a) and Wucheria bancrofti (b). Its effect against macrofilaria adult worms (c) is still uncertain.