Drugs acting on hemoglobin and the oxygen transport system

Norton, James M.; Smith, Roger P.

doi:10.1016/0306-039x(76)90006-4

Cited by 1 publication

(2 citation statements)

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“…Methemoglobinemia (MtHb) is the phenomenon by which PAPP causes its toxic effect. MtHb occurs when the central iron atom of a heme group situated on the hemoglobin protein is oxidized from the ferrous (Fe 2+ ) to is the ferric (Fe 3+ ) form ( Figure 1) (Ash-Bernal et al 2004, Hall et al 1986, Norton and Smith 1976. Hemoglobin a globular protein within red blood cells that acts to deliver oxygen to vital organs such as the brain (Norton and Smith 1976).…”

Section: The Biochemical Mechanism Of Toxicity Of Papp and Papp-like mentioning

confidence: 99%

“…MtHb occurs when the central iron atom of a heme group situated on the hemoglobin protein is oxidized from the ferrous (Fe 2+ ) to is the ferric (Fe 3+ ) form ( Figure 1) (Ash-Bernal et al 2004, Hall et al 1986, Norton and Smith 1976. Hemoglobin a globular protein within red blood cells that acts to deliver oxygen to vital organs such as the brain (Norton and Smith 1976). This oxidation of the iron atom situated on the heme causes a 'left shift' in the oxygen dissociation curve, which essentially results in a higher affinity for O 2 by the remaining heme iron, which in turn causes the hemoglobin to loses its ability to combine reversibly with molecular oxygen ( Martin et al 1995).…”

Section: The Biochemical Mechanism Of Toxicity Of Papp and Papp-like mentioning

confidence: 99%

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Toxicodynamics of Methemoglobin (MtHb) Inducers

Conole¹,

Brimble²,

Rennison³

et al. 2010

vertebrate_pest_conference

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There is a need in New Zealand for a new, more advanced generation of toxins to minimize the impact of invasive animals. A new pest control agent, para-aminopropiophenone (PAPP), represents a lead candidate presently undergoing registration for the humane control of stoats and feral cats. It exhibits low toxicity to most bird species, no secondary poisoning risk, and has a simple and highly effective antidote. PAPP induces methemoglobinemia (MtHb), which acts to prevent oxygen from binding to red blood cells. This reduces oxygen supply to the brain, causing animals to become lethargic, sleepy, and unconscious prior to eventual death in 1 to 2 hours. Despite such promise, to date no previous study has comprehensively examined the effect of modifying the structure of PAPP on MtHb induction. Using PAPP as a platform, this paper describes the design, synthesis, and bioevaluation of PAPP-like red blood cell toxins. The impacts of introducing groups of varying electronic nature at different positions on the PAPP molecule are presently being evaluated. Analogues are synthesized and their MtHb-inducing properties determined using an in vitro assay to establish a formal structure-activity profile. In vivo evaluation in rats is used to assess both their acute toxicity and humaneness of potential candidates. Structure-activity profiles are discussed with the objective of optimizing the bioavailability and potency of PAPP-like compounds to target, high priority pests, particularly rodents.

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Section: The Biochemical Mechanism Of Toxicity Of Papp and Papp-like mentioning

confidence: 99%