tcsc0720 Ivermectin

Ivermectin (MK-933) is a widely used antiparasitic agent in human and veterinary medicine. It is a positive allosteric effector of P2X₄ and the α7 neuronal nicotinic acetylcholine receptor (nAChRs).

In Vitro: Ivermectin (MK-933; IVM) is a specific positive allosteric effector of heterologously expressed P2X₄ and possibly of heteromeric P2X₄/ P2X₆ channels. In the submicromolar range (EC₅₀=250 nM) the action of IVM is rapid and reversible, resulting in increased amplitude and slowed deactivation of P2X₄ channel currents evoked by ATP. Ivermectin (MK-933; IVM) also markedly increases the potency of ATP and that of the normally low-potency agonist a,b-methylene-ATP in a use- and voltage-independent manner without changing the ion selectivity of P2X₄ channels^[1]. Ivermectin (MK-933; IVM) activates glutamate-gated chloride channels in the nerves and muscles of the parasite, leading to membrane hyperpolarization and muscle paralysis. The major mode of action of Ivermectin (MK-933; IVM) is most likely the disruption of ingestive activity of the parasite, resulting in starvation^[2]. Preapplication of ivermectin, in the micromolar range, strongly enhances the subsequent acetylcholine-evoked current of the neuronal chick or human α7 nicotinic acetylcholine receptors reconstituted in Xenopus laevis oocytes and K-28 cells^[3]. Ivermectin activates the rat recombinant α₁β₂γ_2s GABA_A receptor. Activation of the channel with 10 mM GABA results in currents rising within 1 ms to their maximal amplitudes. The EC₅₀ value for GABA is 7.5 μM^[4].