Toxicology Update

Burg, R Von

doi:10.1002/(sici)1099-1263(199909/10)19:5<379::aid-jat563>3.0.co;2-8

Cited by 106 publications

(33 citation statements)

References 31 publications

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“…CO-RM-3 and CO-RM-A1, pharmacologic effects were observed without altering the serum COHb levels. 33-35 The lethal dose of CO is reported to be over 50% COHb, 36, 37 but some animal studies suggest that 50% COHb is far from lethal. 38 As a result, the safety margin is well over 10-fold in many applications.…”

Section: Co Pharmacology and Drug Delivery Issuesmentioning

confidence: 99%

Toward Carbon Monoxide–Based Therapeutics: Critical Drug Delivery and Developability Issues

Damera

Zheng

et al. 2016

Journal of Pharmaceutical Sciences

164

143

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Carbon monoxide is an intrinsic signaling molecule with importance on par with that of nitric oxide. During the past decade, pharmacological studies have amply demonstrated the therapeutic potential of carbon monoxide. However, such studies were mostly based on CO inhalation and metal-based CO releasing molecules (CO-RMs). The field is now at the stage that a major effort is needed to develop pharmaceutically acceptable forms of CO for delivery via various routes such as oral, injection, infusion, or topical applications. This review examines the state of the art, discusses existing hurdles to overcome, and proposes developmental strategies necessary to address remaining drug delivery issues.

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Section: Co Pharmacology and Drug Delivery Issuesmentioning

confidence: 99%

Toward Carbon Monoxide–Based Therapeutics: Critical Drug Delivery and Developability Issues

Damera

Zheng

et al. 2016

Journal of Pharmaceutical Sciences

164

143

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“…Binding of CO to subunits of hemoglobin also increases the affinity for O 2 binding, thus inhibiting O 2 release. Even though this process is reversible, it can lead to CO poisoning [355, 356]. Another potential target of CO is the cytochrome P450 family of enzymes.…”

Section: Carbon Monoxide and Hydrogenmentioning

confidence: 99%

Biological signaling by small inorganic molecules

Basudhar

Ridnour

Cheng

et al. 2016

Coordination Chemistry Reviews

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Small redox active molecules such as reactive nitrogen and oxygen species and hydrogen sulfide have emerged as important biological mediators that are involved in various physiological and pathophysiological processes. Advancement in understanding of cellular mechanisms that tightly regulate both generation and reactivity of these molecules is central to improved management of various disease states including cancer and cardiovascular dysfunction. Imbalance in the production of redox active molecules can lead to damage of critical cellular components such as cell membranes, proteins and DNA and thus may trigger the onset of disease. These small inorganic molecules react independently as well as in a concerted manner to mediate physiological responses. This review provides a general overview of the redox biology of these key molecules, their diverse chemistry relevant to physiological processes and their interrelated nature in cellular signaling.

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“…Direct clinical toxicity of high doses of inhaled CO has been known for decades, and the underlying mechanisms are primarily attributed to the high affinity of CO for hemoglobin and the unfavourable competition with oxygen that is essential for tissue respiration (Yoon et al 1998;Von Burg 1999;Gorman et al 2003). On the other hand, a host of clinical conditions with complex and enigmatic aetiologies are associated with excessive upregulation of HO and the products of its metabolic activity (iron, CO, and bilirubin) and are discussed in the following.…”

Section: Excessive Activation Of the Ho/co System And Potential Applimentioning

confidence: 99%

Inhibitors of the heme oxygenase – carbon monoxide system: on the doorstep of the clinic?

Kinobe

Dercho

Nakatsu

2008

Can. J. Physiol. Pharmacol.

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The past decade has seen substantial developments in our understanding of the physiology, pathology, and pharmacology of heme oxygenases (HO), to the point that investigators in the field are beginning to contemplate therapies based on administration of HO agonists or HO inhibitors. A significant amount of our current knowledge is based on the judicious application of metalloporphyrin inhibitors of HO, despite their limitations of selectivity. Recently, imidazole-based compounds have been identified as potent and more selective HO inhibitors. This 'next generation' of HO inhibitors offers a number of desirable characteristics, including isozyme selectivity, negligible effects on HO protein expression, and physicochemical properties favourable for in vivo distribution. Some of the applications of HO inhibitors that have been suggested are treatment of hyperbilirubinemia, neurodegenerative disorders, certain types of cancer, and bacterial and fungal infections. In this review, we address various approaches to altering HO activity with a focus on the potential applications of second-generation inhibitors of HO.

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Toxicology Update

Cited by 106 publications

References 31 publications

Toward Carbon Monoxide–Based Therapeutics: Critical Drug Delivery and Developability Issues

Toward Carbon Monoxide–Based Therapeutics: Critical Drug Delivery and Developability Issues

Biological signaling by small inorganic molecules

Inhibitors of the heme oxygenase – carbon monoxide system: on the doorstep of the clinic?

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