Ivermectin

Positive allosteric modulator of the α7 neuronal nicotinic acetylcholine receptor and the purinergic P2X₄ receptor. Antihelmintic. Also modulates glutamate- and GABA-activated chloride channels. Potentiates glycine-gated currents at low co

Efficacy of Moxidectin Versus Ivermectin Against Strongyloides stercoralis Infections: A Randomized, Controlled Noninferiority Trial.[Pubmed:28369530]

Clin Infect Dis. 2017 Jul 15;65(2):276-281.

Background: Infections with Strongyloides stercoralis are of considerable public health relevance. Moxidectin, a well-established drug in veterinary medicine under consideration for regulatory submission for the treatment of onchocerciasis, might serve as an alternative to the widely used Ivermectin. Methods: We conducted an exploratory, randomized, single-blind trial to evaluate the efficacy and safety of moxidectin (8 mg) vs Ivermectin (200 mug/kg) against S. stercoralis infections. Cure rate (CR) against S. stercoralis was the primary outcome. Safety and efficacy against coinfections with soil-transmitted helminths and Opisthorchis viverrini were secondary outcomes. Noninferiority required the lower limit of the 95% confidence interval (CI) of the differences in CRs not exceed 7 percentage points. Results: A total of 127 participants were enrolled and randomly assigned to the 2 treatments whereby 1 participant per arm was lost to follow-up. We observed a CR of 93.7% (59/63) for moxidectin compared to 95.2% (59/62) for Ivermectin. Differences between CRs were estimated as -1.5% percentage points (95% CI, -9.6 to 6.5), thus the lower limit of the CI exceeds the noninferiority margin of 7 percentage points. No side effects were observed. CRs against hookworm infection were 57% (moxidectin) and 56% (Ivermectin). Low efficacy for both drugs against O. viverrini was observed. Conclusions: Moxidectin might be a safe and efficacious alternative to Ivermectin for the treatment of S. stercoralis infection, given that only slight differences in CRs were observed. However, noninferiority could not be demonstrated. Larger clinical trials should be conducted once the drug is marketed. Clinical Trials Registration: Current Controlled Trials: ISRCTN11983645.

TREATMENT OF PULMONICOLA COCHLEOTREMA INFECTION WITH IVERMECTIN-PRAZIQUANTEL COMBINATION IN AN ANTILLEAN MANATEE (TRICHECHUS MANATUS MANATUS).[Pubmed:28363040]

J Zoo Wildl Med. 2017 Mar;48(1):217-219.

The aim of this study was to report the use of an oral combination of Ivermectin plus praziquantel in the treatment of a Pulmonicola cochleotrema in an Antillean manatee ( Trichechus manatus manatus). A female manatee was found exhibiting respiratory changes and the presence of parasites in the nares. Based on clinical manifestations presented by the manatee, a symptomatic therapeutic protocol was employed, which included an anthelmintic treatment using a combination of Ivermectin plus praziquantel. The parasites retrieved were identified as P. cochleotrema. The fourth day after the onset of the therapeutic protocol, the clinical signs declined and on the seventh day posttreatment no clinical signs were observed. This is the first time a therapeutic protocol of Ivermectin plus praziquantel has been used in the treatment of P. cochleotrema in manatees.

Posttreatment Reactions After Single-Dose Diethylcarbamazine or Ivermectin in Subjects With Loa loa Infection.[Pubmed:28329346]

Clin Infect Dis. 2017 Apr 15;64(8):1017-1025.

Background: Severe adverse reactions have been observed in individuals with Loa loa infection treated with either diethylcarbamazine (DEC), the drug of choice for loiasis, or Ivermectin (IVM), which is used in mass drug administration programs for control of onchocerciasis and lymphatic filariasis in Africa. In this study, posttreatment clinical and immunologic reactions were compared following single-dose therapy with DEC or IVM to assess whether these reactions have the same underlying pathophysiology. Methods: Twelve patients with loiasis and microfilarial counts <2000 mf/mL were randomized to receive single-dose DEC (8 mg/kg) or IVM (200 microg/kg). Clinical and laboratory assessments were performed at 4, 8, 24, 48, and 72 hours and 5, 7, 9, and 14 days posttreatment. Results: Posttreatment adverse events were similar following DEC or IVM, but peaked earlier in subjects who received DEC, consistent with a trend toward more rapid and complete microfilarial clearance in the DEC group. After a transient rise (post-IVM) or fall (post-DEC) in the first 24 hours posttreatment, the eosinophil count rose significantly in both groups, peaking at day 5 in the DEC group and day 9 in the IVM group. Serum interleukin 5 levels and eosinophil activation, as assessed by surface expression of CD69 and serum levels of eosinophil granule proteins, were increased posttreatment in both groups. Conclusions: Despite differences in eosinophil and lymphocyte counts during the first 24 hours posttreatment, the overall pattern of hematologic and immunologic changes suggest that posttreatment reactions following DEC and IVM share a common pathophysiology. Clinical Trials Registration: NCT01593722.

Ivermectin alters reproductive success, body condition and sexual trait expression in dung beetles.[Pubmed:28324834]

Chemosphere. 2017 Jul;178:129-135.

Ivermectin is a very common parasiticide used in livestock. It is excreted in the dung and has negative effects on survival and reproduction of dung-degrading organisms, including dung beetles. Here we exposed the dung beetle Euoniticellus intermedius to different concentrations of Ivermectin in the food and evaluated reproductive success and the expression of traits associated with survival and reproduction under laboratory conditions. It is the first time the effects of Ivermectin were evaluated on offspring physiological condition and the expression of a secondary sexual trait. We also registered the number of emerged beetles, sex ratio and body size of emerged adult beetles. Besides reducing the number of emerged beetles and body size, as found in the same and other insects, Ivermectin at high doses reduced muscle mass while at intermediate doses it increased lipid mass. Ivermectin changed offspring sex ratio and at high doses increased the size of male horn, which is an important trait defining the male mating success. Our results highlight the importance of regulating parasiticide usage in livestock in order to maintain ecosystem services provided by dung beetles and confirm that contaminants impose new environmental conditions that not only impact on wild animal survival, but also on evolutionary processes such as sexual selection.

Ivermectin, an unconventional agonist of the glycine receptor chloride channel.[Pubmed:11278873]

J Biol Chem. 2001 Apr 20;276(16):12556-64.

The effects of the antihelmintic, Ivermectin, were investigated in recombinantly expressed human alpha(1) homomeric and alpha(1)beta heteromeric glycine receptors (GlyRs). At low (0.03 microm) concentrations Ivermectin potentiated the response to sub-saturating glycine concentrations, and at higher (> or =0.03 microm) concentrations it irreversibly activated both alpha(1) homomeric and alpha(1)beta heteromeric GlyRs. Relative to glycine-gated currents, Ivermectin-gated currents exhibited a dramatically reduced sensitivity to inhibition by strychnine, picrotoxin, and zinc. The insensitivity to strychnine could not be explained by Ivermectin preventing the access of strychnine to its binding site. Furthermore, the elimination of a known glycine- and strychnine-binding site by site-directed mutagenesis had little effect on Ivermectin sensitivity, demonstrating that the Ivermectin- and glycine-binding sites were not identical. Ivermectin strongly and irreversibly activated a fast-desensitizing mutant GlyR after it had been completely desensitized by a saturating concentration of glycine. Finally, a mutation known to impair dramatically the glycine signal transduction mechanism had little effect on the apparent affinity or efficacy of Ivermectin. Together, these findings indicate that Ivermectin activates the GlyR by a novel mechanism.

Activation of rat recombinant alpha(1)beta(2)gamma(2S) GABA(A) receptor by the insecticide ivermectin.[Pubmed:10771281]

Eur J Pharmacol. 2000 Apr 14;394(2-3):163-70.

In the present study, the activation of rat recombinant alpha(1)beta(2)gamma(2S) gamma-aminobutyric acid (GABA)-ergic Cl(-) channel expressed in human embryonic kidney (HEK) 293 cells by Ivermectin was investigated. Maximal activation of the channel occurred with GABA concentrations of 10 mM or 20 microM Ivermectin both achieving about the same current amplitudes. With those saturating concentrations, the currents rose with GABA within 1 ms to the maximal values, whereas the rise time for Ivermectin was about 500 times longer. In contrast to activation with GABA, no desensitisation in the presence of the agonist was observed with Ivermectin. With both agonists, two different open states were detected. On simultaneous application of GABA and Ivermectin the current amplitudes and the kinetics were determined by the agonist applied in the concentration eliciting the higher open probability. It is concluded that GABA and Ivermectin activated the channel independently resulting in different kinetic properties.

Allosteric control of gating and kinetics at P2X(4) receptor channels.[Pubmed:10460235]

J Neurosci. 1999 Sep 1;19(17):7289-99.

The CNS abundantly expresses P2X receptor channels for ATP; of these the most widespread in the brain is the P2X(4) channel. We show that Ivermectin (IVM) is a specific positive allosteric effector of heterologously expressed P2X(4) and possibly of heteromeric P2X(4)/P2X(6) channels, but not of P2X(2), P2X(3), P2X(2)/P2X(3,) or P2X(7) channels. In the submicromolar range (EC(50,) approximately 250 nM) the action of IVM was rapid and reversible, resulting in increased amplitude and slowed deactivation of P2X(4) channel currents evoked by ATP. IVM 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. Therefore, IVM evokes a potent pharmacological gain-of-function phenotype that is specific for P2X(4) channels. We also tested whether IVM could modulate endogenously expressed P2X channels in the adult trigeminal mesencephalic nucleus and hippocampal CA1 neurons. Surprisingly, IVM produced no significant effect on the fast ATP-evoked inward currents in either type of neuron, despite the fact that IVM modulated P2X(4) channels heterologously expressed in embryonic hippocampal neurons. These results suggest that homomeric P2X(4) channels are not the primary subtype of P2X receptor in the adult trigeminal mesencephalic nucleus and in hippocampal CA1 neurons.

Ivermectin: a positive allosteric effector of the alpha7 neuronal nicotinic acetylcholine receptor.[Pubmed:9463487]

Mol Pharmacol. 1998 Feb;53(2):283-94.

We report that preapplication of Ivermectin, in the micromolar range, strongly enhances the subsequent acetylcholine-evoked current of the neuronal chick or human alpha7 nicotinic acetylcholine receptors reconstituted in Xenopus laevis oocytes and K-28 cells. This potentiation does not result from nonspecific Cl- currents. The concomitant increase in apparent affinity and cooperativity of the dose-response curve suggest that Ivermectin acts as a positive allosteric effector. This interpretation is supported by the observation of an increase in efficiency of a partial agonist associated with the potentiation and by the differential effect of Ivermectin on mutants within the M2 channel domain. Ivermectin effects reveal a novel allosteric site for pharmacological agents on neuronal alpha7 nicotinic acetylcholine receptors.

Ivermectin (MK-933) is a broad-spectrum anti-parasite medication used in humans most commonly to treat nematode infections such as onchocerciasis, as well as scabies and lice. Ivermectin (MK-933) is a specific inhibitor of Impα/β1-mediated nuclear import and has potent antiviral activity towards both HIV-1 and dengue virus. It is a positive allosteric effector of P2X4 and the α7 neuronal nicotinic acetylcholine receptor (nAChRs). Ivermectin also inhibits bovine herpesvirus1 (BoHV-1) replication and inhibits BoHV-1 DNA polymerase nuclear import.

Ivermectin,70288-86-7,22,23-Dihydroavermectin B1,Natural Products,P2X purinergic receptor, buy Ivermectin , Ivermectin supplier , purchase Ivermectin , Ivermectin cost , Ivermectin manufacturer , order Ivermectin , high purity Ivermectin