Avermectins and milbemycins

McKellar, Quintin; Benchaoui, H. A.

doi:10.1111/j.1365-2885.1996.tb00062.x

Cited by 262 publications

(203 citation statements)

References 149 publications

(44 reference statements)

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“…Although a significant correlation was observed between the administered IVM doses and the IVM plasma concentrations, large variations in plasma concentration were present within the same treatment doses. A similar pharmacokinetic variability in the IVM plasma profiles has also been observed in other studies (McKellar and Benchaoui, 1996;Lanusse et al, 1997) and can be attributed to differences in breed, the site of IVM injection (muscle or fat tissue), the extent and rate of absorption, availability of the drug, metabolism and body composition, diet intake and body condition (Hennessy and Alvinerie, 2002).…”

Section: Discussionmentioning

confidence: 57%

Experimental selection for ivermectin resistance in Ostertagia ostertagi in cattle

Zeveren

Casaert

Alvinerie³

et al. 2007

Veterinary Parasitology

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Recent reports of suspected ivermectin (IVM) resistance in Ostertagia ostertagi have highlighted the need for research into the mechanisms of IVM resistance. However, there are no reports of resistant field isolates of O. ostertagi, which have been characterized for molecular research. Therefore, an anthelmintic susceptible O. ostertagi population was selected for IVM resistance by repeatedly exposing the population to subtherapeutic and therapeutic levels of IVM over 10 generations. In each selection round, a group of calves was infected with the progeny of the previous IVM-selected O. ostertagi population. In the last selection round a therapeutic IVM dose (0.2 mg/kg BW) only reduced the faecal egg counts by 57% and 65% on days 7 and 14 after treatment, respectively. In contrast, the therapeutic IVM dose was 100% effective at eliminating the parental IVM-susceptible isolate. #

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Section: Discussionmentioning

confidence: 57%

Experimental selection for ivermectin resistance in Ostertagia ostertagi in cattle

Zeveren

Casaert

Alvinerie³

et al. 2007

Veterinary Parasitology

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“…Of the analogues investigated here, only moxidectin exhibited a higher potency than ivermectin, although the difference was not statistically significant ( Table 2). Moxidectin is a milbemycin, which are aglycones of the avermectins, and these have remarkably fewer side effects than avermectins such as ivermectin (40). Indeed, it is predominantly for this reason that moxidectin is currently being tested in human clinical trials for river blindness (41).…”

Section: Discussionmentioning

confidence: 99%

An Improved Ivermectin-activated Chloride Channel Receptor for Inhibiting Electrical Activity in Defined Neuronal Populations

Lynagh¹,

Lynch

2010

Journal of Biological Chemistry

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The ability to silence the electrical activity of defined neuronal populations in vivo is dramatically advancing our understanding of brain function. This technology may eventually be useful clinically for treating a variety of neuropathological disorders caused by excessive neuronal activity. Several neuronal silencing methods have been developed, with the bacterial lightactivated halorhodopsin and the invertebrate allatostatin-activated G protein-coupled receptor proving the most successful to date. However, both techniques may be difficult to implement clinically due to their requirement for surgically implanted stimulus delivery methods and their use of nonhuman receptors. A third silencing method, an invertebrate glutamate-gated chloride channel receptor (GluClR) activated by ivermectin, solves the stimulus delivery problem as ivermectin is a safe, well tolerated drug that reaches the brain following systemic administration. However, the limitations of this method include poor functional expression, possibly due to the requirement to coexpress two different subunits in individual neurons, and the nonhuman origin of GluClR. Here, we describe the development of a modified human ␣1 glycine receptor as an improved ivermectin-gated silencing receptor. The crucial development was the identification of a mutation, A288G, which increased ivermectin sensitivity almost 100-fold, rendering it similar to that of GluClR. Glycine sensitivity was eliminated via the F207A mutation. Its large unitary conductance, homomeric expression, and human origin may render the F207A/A288G ␣1 glycine receptor an improved silencing receptor for neuroscientific and clinical purposes. As all known highly ivermectin-sensitive GluClRs contain an endogenous glycine residue at the corresponding location, this residue appears essential for exquisite ivermectin sensitivity.Several methods for silencing neuronal electrical activity in behaving animals have been developed that could eventually be useful for treating neurological disorders including Parkinson disease, addiction, epilepsy, depression, and chronic pain states (1, 2). Generally, these techniques involve overexpressing an exogenous receptor in molecularly or spatially defined populations of neurons and applying a specific stimulus to activate this receptor and thereby silence the neurons.The two most successful strategies to date have proved to be bacterial halorhodopsin and the Drosophila allatostatin receptor. Halorhodopsin is a light-activated inward chloride pump, which, when exogenously expressed in neurons, hyperpolarizes neurons rapidly and reversibly upon the application of intense yellow light (3). Although this has been employed successfully to correlate neuronal activity with behavior (4), it is limited by 1) the requirement for strong overexpression and 2) the necessity to deliver intense light to neurons in vivo. The recent development of more efficient light-driven outward proton pumps may address the first limitation (5).The alternate approach employs a Drosophila G pro...

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“…The mode of action of the different ML endectocides is similar at any rate in that it is not totally understood (McKellar & Benchaoui, 1996). Efficacy has been demonstrated against nematodes and arthropods, with some exceptions, such as the nematode Thelazia lacrymalis and the mite Ornithonyssus sylviarum (Campbell & Benz, 1984).…”

Section: Mode Of Actionmentioning

confidence: 96%

“…Pharmacokinetics of ivermectin in domestic ruminants has been reviewed by Bennett (1986) and Steel (1993) and of various ML endectocides by McKellar & Benchaoui (1996). The ivermectin absorbed to the circulation is almost totally excreted in the bile.…”

Section: Pharmacokinetics and Route Of Applicationmentioning

confidence: 99%

Synopsis

Oksanen¹

1999

Ran

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Avermectins and milbemycins

Cited by 262 publications

References 149 publications

Experimental selection for ivermectin resistance in Ostertagia ostertagi in cattle

Experimental selection for ivermectin resistance in Ostertagia ostertagi in cattle

An Improved Ivermectin-activated Chloride Channel Receptor for Inhibiting Electrical Activity in Defined Neuronal Populations

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