Current Pharmaceutical Biotechnology - Volume 13, Issue 6, 2012

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Carbon monoxide (CO) is a colourless and odourless gas that has long been considered as a potent respiratory poison. Recent advances have demonstrated its production by haem oxygenases in both mammals and microbes, and it has roles as a gasotransmitter in higher organisms. This review concentrates on the application of CO, via carbon monoxidereleasing molecules (CO-RMs), as an anti-bacterial agent. Currently, t Read More

Chronic obstructive pulmonary disease (COPD) is a disease involving airways restriction, alveolar destruction, and loss of lung function, primarily due to cigarette smoke (CS) exposure. The inducible stress protein heme oxygenase-1 (HO-1) has been implicated in cytoprotection against the toxic action of many xenobiotics, including CS. HO-1 also protects against elastase-induced emphysema. Differential expression of HO-1 Read More

Despite modern clinical practice in critical care medicine, acute lung injury still causes unacceptably high rates of morbidity and mortality. Therefore, the challenge today is to identify new and effective strategies in order to improve the outcome of these patients. Carbon monoxide, endogenously produced by the heme oxygenase enzyme system, has emerged as promising gaseous therapeutic that exerts protective Read More

During the degradation of heme by the enzyme heme oxygenase (HO), Carbon monoxide (CO) is generated. Although it is considered as a non - significant and potentially toxic waste gas of heme catabolism, CO is a key signaling molecule used to regulate different cardiovascular functions. In this review, we focus the protective roles of CO in vascular injury/disease, which may be important to explore the overall protective role Read More

Although a potentially toxic gaseous molecule, carbon monoxide recently gains rising scientifically and clinical interest as its beneficial effects and mechanisms of action are defined substantially in various in vitro and in vivo experiments. Its anti-inflammatory, anti-apoptotic and anti-proliferative properties but its increasing impact concerning numerous disease models in means of protection, well describe this gas as Read More

Carbon monoxide is generally believed to be a ‘toxic’ gas molecule due to its binding capability with hemoglobin. Overexposure to carbon monoxide leads to a hypoxic state that may cause the death of a mammalian. In contrast, directly exposure of carbon monoxide may protect cells or organs from various disease insults. The paradox effects of carbon monoxide might vary on the ways of exposure and the amounts being expos Read More

Carbon monoxide (CO), often referred to as the silent killer, is a colorless, odorless and tasteless gas. It combines with hemoglobin to produce carboxyhemoglobin, which is ineffective for delivering oxygen to animal and human tissues. On the other hand, CO is endogenously produced in the body as a byproduct of heme degradation catalyzed by the heme oxygenase (HO) enzymes. In the past decade, evidence has accumula Read More

Carbon monoxide (CO) is an endogenously produced gas resulting from the degradation of heme by heme oxygense or from fatty acid oxidation. Heme oxygenase (HO) enzymes are constitutively expressed in the kidney (HO-2) and HO-1 is induced in the kidney in response to several physiological and pathological stimuli. While the beneficial actions of HO in the kidney have been recognized for some time, the importa Read More

Carbon monoxide (CO) is an invisible, chemically inert, colorless and odorless gas and is toxic at high concentrations due to its interference with oxygen delivery. However, CO is endogenously and physiologically generated in mammalian cells via the catabolism of heme in a rate-limiting step of heme oxygenase systems, and CO potently protects against cellular injury. CO relaxes blood vessels and exerts anti-thrombotic effect Read More

Carbon monoxide (CO) has long been considered a purely toxic by-product of incomplete combustion processes. Acute exposure to high concentrations of CO is one of the leading causes of fatal poisoning in industrial countries. However, after two decades of intensive research, there is ample evidence that CO endogenously produced by heme oxygenase enzymes has essential physiological functions and is of vital imp Read More

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The macrocyclic lactones enjoy a position of prominence in the control of parasites, and their history may be of interest, and even of use, in an age in which the search for chemotherapeutic agents has been transformed by modern technology. Much of their history has been recorded piecemeal in a wide variety of publications. The present review provides additional detail, and offers a personal perspective on the history of iverm Read More

Macrocyclic lactones (MLs), exemplified by the prototype of the class, ivermectin (IVM), are mainstays of programs for the control of nematode and arthropod parasites and pests. Since their introduction 30 years ago, research has revealed that they act on a family of ligand-gated chloride channels gated by glutamate, which is largely restricted to animals in the phyla Nematoda and Arthropoda. Studies on IVM in model org Read More

Resistance to the macrocyclic lactones (MLs) has been confirmed or suspected in many target organisms and is a serious problem in some. For some species, such as parasitic nematodes of small ruminants, ML resistance has become severe enough to threaten effective worm control worm control. Resistance is also a major concern in horse parasites and an emerging problem in cattle. Despite this, we have insufficient unde Read More

The macrocyclic lactones have pharmacokinetic properties which enhance their use against endo- and ectoparasites in animals and man. The most consistent physico-chemical feature of the group which contributes to their kinetic characteristics is high lipid solubility. This appears to be necessary for their pharmacodynamic action as well as common kinetic features such as large volumes of distribution and the influence Read More

Macrocyclic lactones (MLs) are antiparasitic drugs used against endo-ectoparasites. Regarding the wide use of MLs in different species, it is likely that drug-drug interactions may occur after their co-administration with other compounds. A new paradigm was introduced in the study of the pharmacology of MLs during the last years since the interactions of MLs with ATP-binding cassete (ABC) transporters have been describe Read More

The characterisation of ivermectin pharmacokinetics can be used to predict and to ensure an optimal activity in the target species and for designing programmes aimed for parasite control. Ivermectin pharmacokinetic studies performed in several minor ruminant species are reviewed in this paper with the aim of facilitating the adoption of rational basis for the establishment of appropriate dosage schedules.

A review of the developments on the analysis of residues of avermectins and milbemycins (both macrocyclic lactones) is presented. The macrocyclic lactones (MLs) are an important class of chemicals, which are used worldwide as veterinary drugs and as crop protection agents. As a result, residues of MLs are important from both a food safety and environmental perspective. A review of the developments in ML resid Read More

The macrocyclic lactone endectocides typified by ivermectin are safe and effective drugs when used according to label directions. However, off-label use, misuse and overdosing can result in toxicity in animal patients as revealed by pharmacovigilance activities. Preclinical toxicity studies demonstrates that the major clinical signs of toxicity are those associated with neurotoxic effects and these are the most common adve Read More

P-glycoprotein, encoded by the multidrug resistance gene MDR1, is an ATP-driven drug efflux pump which is highly expressed at the blood-brain barrier of vertebrates. Drug efflux of macrocyclic lactones by P-glycoprotein is highly relevant for the therapeutic safety of macrocyclic lactones, as thereby GABA-gated chloride channels, which are confined to the central nervous system in vertebrates, are protected from high drug c Read More

From a human safety perspective, the administration of ivermectin to food producing animal species entails potential risks related to the presence of drug residues in edible tissues, milk, and other derived products. The European Medicines Agency has established the maximum residue limits for ivermectin in the European Union, with values of 100 μg·kg-1 in fat and liver and 30 μg·kg-1 in kidney for all mammalian food produc Read More

Macrocyclic lactones, including avermectins and milbemycins, are novel parasiticides and insecticides that are produced through fermentation by soil-dwelling microorganisms. Although various macrocyclic lactones may differ in their potency and safety, all of them are believed to share common pharmacologic/toxicologic mechanisms, i.e. leading to paralysis and death of parasites and other target organisms via the acti Read More

The avermectins, milbemycins and spinosyns are collectively referred to as macrocyclic lactones (MLs) which comprise several classes of chemicals derived from cultures of soil micro-organisms. These compounds are extensively and increasingly used in veterinary medicine and agriculture. Due to their potential effects on non-target organisms, large amounts of information on their impact in the environment has been compiled i Read More

The use of macrocyclic lactones has become the main stay for the treatment of endo- and ectoparasites in the cattle industry. Here we review those drugs that are currently approved for use in cattle in the United States. The general efficacy, tissue distribution and toxicity of each drug formulation are discussed. Included is a discussion regarding the current status for nematode anthelmintic resistance in cattle populatio Read More

Macrocyclic lactones (MLs) revolutionized parasite control in horses and other animals. They are unique in that they are effective against arthropods and nematodes. The first of the widely used avermectins was ivermectin. In 1983, it was marketed for use in horses as an injectable formulation but was withdrawn in 1984 after about a year and half on the market because of adverse problems. It was replaced by a pa Read More

Macrocyclic lactones (MLs) have many anti-parasitic applications in small companion animal medicine. They were first developed as chemoprophylactics against heartworm (Dirofilaria immitis) infection to be applied monthly for retroactive killing of third- and fourth-stage larvae. ML-containing products formulated for oral (ivermectin, milbemycin oxime), topical (selamectin, moxidectin) or injectable sustained rele Read More

The main indication for use of avermectins in aquaculture-produced fish is infestations with ectoparasitic copepods. The compounds ivermectin and emamectin benzoate are predominantly used as in-feed formulations on salmonid fish against copepods in the family Caligidae: Lepeophtheirus salmonis, Caligus elongatus and C. rogercresseyi. These agents are well-documented as very effective on all developmental stages of th Read More

Ivermectin is a broad spectrum antiparasitic veterinary drug introduced in human medicine in 1987. It is considered the drug of choice in onchocerciasis and strongyloidiasis infections, and remains as a therapeutic option for mass treatment in lymphatic filariasis, for which it has widely proved its efficacy. While research continued for human use, new therapeutic targets for ivermectin have emerged. It is currently the be Read More

The donation of Mectizan® by Merck & Co Inc. in 1987 “as much as was needed for as long as was needed for onchocerciasis control” was a major change from traditional corporate drug donations. The company realised that those who needed the drug most would never be able to purchase it, and so gave it away. The donation enabled the Onchocerciasis Control Programme in West Africa to add Mectizan distribution to its ongo Read More