| 描述 |
Ivermectin (IVM), a widely used antiparasitic agent in human and veterinary medicine. Ivermectin (MK-933) activates glutamate-gated chloride channels in the nerves and muscles of the parasite, leading to membrane hyperpolarization and muscle paralysis[3]. Ivermectin is a specific positive allosteric effector of heterologously expressed P2X(4) and possibly of heteromeric P2X(4)/P2X(6) channels. In the submicromolar range (EC50 = 250 nM) the action of Ivermectin is rapid and reversible, resulting in increased amplitude and slowed deactivation of P2X4 channel currents evoked by ATP. Ivermectin also markedly increased the potency of ATP and that of the normally low-potency agonist alpha, beta-methylene-ATP in a use- and voltage-independent manner without changing the ion selectivity of P2X(4) channels[4]. Ivermectin has potent antiviral activity towards both HIV-1 and dengue virus, both of which are strongly reliant on importin α/β nuclear import, with respect to the HIV-1 integrase and NS5 (non-structural protein 5) polymerase proteins respectively. Ivermectin strongly inhibits the binding of Impα/β1 to NS5 (IC50 = 17 μM), but not of Impβ1 alone to NS5[5]. Ivermectin also inhibits bovine herpesvirus 1 (BoHV-1) replication and inhibits BoHV-1 DNA polymerase nuclear import[6]. |
