Index:Astrazeneca stroke renovis cerovive nitrone.
Peter H. Proctor, PhD, MD
This website covers the biological and therapeutic aspects of nitroxide spin labels and nitrone spin traps. One example is Cerovive, Astrazenca's new stroke drug.
Briefly, nitroxides and nitrones are stabilized forms of the biological messenger nitric oxide. They also have some unique properties. e.g. unlike other antioxidants, they generally neither act as proxidants, nor do they propagate free radical chain reactions.
Likewise, these agents inhibit the reaction of superoxide and nitric oxide to produce peroxinitrite. Recent evidence suggests that this reaction may play a crucial role in a wide range of degenerative diseases. These include Parkinsonism, stroke, ischaemic injury, heart attack, and age-related dementias.
Similarly, free radicals are also important, often extracellular, "redox" signaling messengers and this is likely responsible for much "cellular dysfunction" . Thus, many of the actions of the archetype spin trap, PBN or its disulfonic acid derivative ( AstraZeneca's "Cerovive" ), are likely explicable in terms of redox-signaling-mediated processes. One example is the effect of such compounds on cytokines such as TNF alpha. Similarly, the redox-modulated ion channel TRPM7 may play a key role in neuronal death in stroke.
Because they inhibit fundamental pathogenic mechanisms, these drugs are extremely promising for the treatment of inflammatory and degenerative diseases such as the senile dementias, parkinsonism, cancer, stroke, etc. The archetype nitrone drug, PBN, uniquely extends maximum lifespan in experimental animals. For a summary of such diseases and pathogenic processes, read my review article " Free Radicals and Human Disease ",
E.g., US patent 5,732,502 (covering use of PBN and other nitrones as drugs) claims " other free radical diseases as outlined in Proctor et al., "Free Radicals and Disease in Man," Physiological Chemistry and Physics and Medical NMR, volume 16, pp. 175-195 (1984) which is hereby incorporated herein by reference; and the like." Click Free radicals and Disease for a copy of this review article.
Stroke--- Decades ago, Demopolous et al reported a role for free radicals etc. in stroke and and ischaemic injury. For a good general review, see " Mechanisms of Action of Neuroprotectants in Stroke ". The disulfonyl derivative of PBN ( phenybutylnitrone ), NXY059 or "Cerovive" (TM) is now in phase-3 clinical trials for stroke For a review (needs signup for full access), see Cerovive.
Peter H. Proctor, PhD, MD
4126 SW Freeway, Suite 1616
Houston, TX 77027
Phone: +1 713 960 1616
FAX: +1 713 960 1616
Email: drp@drproctor.com
Cerovive is the registered trademark of AstraZeneca for NXY-059, the disulfonyl derivative of phenylbutylnitrone (PBN).
homocysteine redox.
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homocysteine redox Keywords antioxidant free radical organic semiconductors trpm7 alzheimers multiinfarct dementia superoxide ros reperfusion injury reperfusion injury peroxide catalase sod dismutase astrazenica (sp) signaling thiolactone cancer treatment redox vascular musculoskeletal disorder.
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