Action Of Avermectins Research Articles

Inhibition of Plasmodium sporogonic stages by ivermectin and other avermectins

BackgroundThe transmissible forms of Plasmodium parasites result from a process of sporogony that takes place inside their obligatory mosquito vector and culminates in the formation of mammalian-infective parasite forms. Ivermectin is a member of the avermectin family of endectocides, which has been proposed to inhibit malaria transmission due its insecticidal effect. However, it remains unclear whether ivermectin also exerts a direct action on the parasite’s blood and transmission stages.MethodsWe employed a rodent model of infection to assess the impact of ivermectin treatment on P. berghei asexual and sexual blood forms in vivo. We then made use of a newly established luminescence-based methodology to evaluate the activity of ivermectin and other avermectins against the sporogonic stages of P. berghei parasites in vitro independent of their role on mosquito physiology.ResultsOur results show that whereas ivermectin does not affect the parasite’s parasitemia, gametocytemia or exflagellation in the mammalian host, several members of the avermectin family of compounds exert a strong inhibitory effect on the generation and development of P. berghei oocysts.ConclusionsOur results shed light on the action of avermectins against Plasmodium transmission stages and highlight the potential of these compounds to help prevent the spread of malaria.

Acute behavioural and physiological responses of sheep to S/C ivermectin injection

Acute behavioural and physiological responses of sheep to S/C ivermectin injection

Expression of Caenorhabditis elegans mRNA in n Xenopus oocytes: a model system to study the mechanism of action of avermectins.

It has recently been shown that Xenopus oocytes injected with mRNA from the free-living nematode Caenorhabditis elegans express avermectin-sensitive chloride channels. Joseph Arena here reviews what is known about the mechanism of action of avermectin and how these recent results relate to the mechanism in nematodes.

The action of avermectin (MK 936) on identified central neurones from Helix and its interaction with acetylcholine and gamma-aminobutyric acid (GABA) responses

I. Intracellular recordings were made from identified neurones in the suboesophageal ganglionic mass of the snail, Helix aspersa. 2. Avermectin, MK 936, 0.01-1.0 μM, induced an outward current in certain neurones. The size of this current varied from one cell type to another. This direct effect of Avermectin occurred irrespective of whether the neurones were sensitive to GABA or not and was generally irreversible. 3. Avermectin, 0.1 μM, reduced the chloride mediated inhibitory GABA response and potentiated the largely sodium mediated excitatory GABA response. 4. Avermectin, 0.1 μM, reduced the chloride mediated acetylcholine inhibitory response and potentiated the sodium mediated excitatory acetylcholine response. In neurones which showed a biphasic response to acetylcholine, Avermectin enhanced the excitatory and depressed the inhibitory component. 5. It is concluded that Avermectin can interact with chloride ionophores to induce an outward current and can reduce chloride mediated responses associated with acetylcholine and GABA.

Action of avermectin B 1a on the leg muscles and the nervous system of the American cockroach

The action of avermectin was studied in the leg muscle and the central nervous system of the American cockroach, Periplanata americana L. Avermectin at a low concentration (10 −7 M) causes a failure of the leg muscles to respond to external stimuli within 30 min without affecting the magnitude of contraction. Avermectin was found to stimulate Cl − uptake by the leg muscles within 4 min at 10 −7 M. The threshold concentration to cause such stimulation was on the order of 10 −8 M. This stimulatory action could be antagonized by picrotoxinin (10 −4 M) and to a lesser extent by bicuculline methiodide (10 −4 M). The phenomenon is observable under both Na +-free and K +-free conditions. It was concluded that the action of avermectin is to open the chloride channel on the plasma membrane. This action of avermectin does not seem to be mediated through GABA, GABA receptors, diazepine receptors, or picrotoxinin receptor in this insect species, and therefore suggests that avermectin directly attacks the chloride channel proper both in the central nervous and the neuromuscular systems.