Index:Astrazeneca stroke renovis cerovive NXY-059.
Peter H. Proctor, PhD, MD
The spin trap homepage covers the biological and therapeutic aspects of 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. This may acount for the effect of REN-1654, Renovis' drug for neuropathic pain. 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 ",
A Patent Dispute with Centaur
Look here for my patents, etc. on nitrone and nitroxide drugs. While nominally for topical use, these patents also grant general utility for "ameliorating a cellular dysfunction of a tissue". This includes "parenteral" use. Thus, the patents incorporate claims for the treatment of diseases which I had previously listed in review articles.
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 at Astrazeneca. 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.
Finasteridearthritis inflammation endothelium no inos cnos signaling messenger active oxygen deafness nkbeta inner ear cis platinum stria vascularis adriamycin bleomycin pbn nxy-059 astrazenica electron transfer hydroxyl radical catalase peroxidase anticancer high conductivity alcaptonuria phenothiazine dopa uric acid radioprotection radiation treatment melanin lesch-nyhan manganese hemochromatosis iron copper porphyria cancer radiotherapy nkbeta apoptosis
vascular endothelium parkinsonism multiple sclerosis als amylotrophic lateral sclerosis spin trap label tempo tempol dmpo dementia deafness psychosis homocystinuria inflammation cox2
homocysteine redox Keywords antioxidant free radical organic semiconductors trpm7 alzheimers multiinfarct dementia superoxide ros reperfusion injury reperfusion injury (sp) signaling thiolactone cancer treatment redox vascular musculoskeletal disorder.
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