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Medical Forum / General / General / April 2006Novel brain-penetrating antioxidant
Since the PROBLEM with the anti-psychotics IS the .. buildup of iron .. then one might think the 'novel brain-targeted antioxidant ' .. might be an iron .. chelator. Clin Neuropharmacol. 2005 Nov-Dec;28(6):285-8. Related Articles, Links A novel brain-targeted antioxidant (AD4) attenuates haloperidol-induced abnormal movement in rats: implications for tardive dyskinesia. Sadan O, Bahat-Stromza M, Gilgun-Sherki Y, Atlas D, Melamed E, Offen D. Department of Neurology and Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, 49100 Israel. BACKGROUND: Tardive dyskinesia (TD), characterized by abnormal movements, is the major late-onset chronic side effect of antipsychotic treatment found in about 30% of those patients. The association of oxidative stress and the release of free radicals is one of the hallmarks of dopaminergic malfunctions and is one of the leading theories suggested for the pathophysiology of TD. To this day, no brain-targeted antioxidant has been tested as a potential treatment of TD. In light of this assumption, the authors chose a novel, low-molecular weight thiol antioxidant, N-acetyl cysteine amide (AD4), that crosses the blood-brain barrier as a possible treatment of TD. OBJECTIVE: To examine the protective effects of the novel brain-penetrating antioxidant AD4 on TD experimental models. METHODS: The typical vacuous chewing movement occurs in rats following chronic haloperidol injections (1.5 mg/kg/day intraperitoneally for 21 days). This purposeless mouth opening in the vertical plane is similar to TD symptoms in humans. The authors tested rats treated with haloperidol without or with AD4 in the drinking water (1 g/kg orally). Thiobarbituric acid reactive substances and anticarbonyl antibodies were used to measure oxidation of membranes and proteins. RESULTS: Haloperidol increased the vacuous chewing movements to 66.5 +/- 7.6 movements/5 minutes compared with 16.4 +/- 2.4 movements/5 minutes in untreated rats (P < 0.01). Coadministration of haloperidol and AD4 decreased the vacuous chewing movements level to 42.1 +/- 6.7 movements/5 minutes (P < 0.05). Haloperidol also increased the level of lipid peroxidation and protein oxidation in the rat brain, whereas coadministration with AD4 preserved their normal levels. CONCLUSION: Haloperidol causes behavioral abnormalities associated with oxidative stress in rats, similar to TD. AD4, the brain-targeted potent antioxidant, reduces the cellular oxidation markers and improves the typical clinical behavior. Hence, AD4 is a potential new treatment of antipsychotic-induced TD. PMID: 16340385 [PubMed - indexed for MEDLINE] -------------------------------------------------------------------------------- Who loves ya. Tom Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://pages.ivillage.com/ironjustice/manisaherbivore DEAD PEOPLE WALKING http://pages.ivillage.com/ironjustice/deadpeoplewalking "S" No, tk is not the build up of iron. ">>S" No, tk is not the build up of iron.<< Isr J Med Sci 1993 Sep;29(9):587-92 Iron modulates neuroleptic-induced effects related to the dopaminergic system. Ben-Shachar D, Livne E, Spanier I, Zuk R, Youdim MB Department of Pharmacology, B. Rappaport Faculty of Medicine, Technion Haifa, Israel. Long-term neuroleptic medication to schizophrenic patients is often associated with extrapyramidal side effects, of which tardive dyskinesia is the most severe. The mechanism by which neuroleptics induce these side effects is unclear. The dopaminergic system is the main target with which the neuroleptics interact in the brain. Intact dopaminergic function is dependent on normal iron metabolism. Thus, the relationship between iron and the neuroleptics may elucidate some new aspects of their mechanism of action. Indeed, peripheral iron status plays a crucial role in neuroleptic-induced dopamine supersensitivity. Moreover, neuroleptics such as haloperidol and chlorpromazine, alter the blood brain barrier (BBB) of the rat and enhance the normally restricted iron transport into the brain. Increased brain iron levels may be related to the toxic effects of these drugs since clozapine, an atypical neuroleptic with a low incidence of extrapyramidal side effects, prohibits iron uptake into the brain but causes sedimentation of iron in brain blood vessels. The demonstration that peripheral iron concentrations affect neuroleptic-induced dopamine receptor supersensitivity as well as iron transport into the brain may have therapeutic significance. In addition, the different potentials of typical and atypical neuroleptics to increase iron transport into the brain may be related to the severity of the side effects they induce and to the pathophysiology of tardive dyskinesia. Publication Types: Review Review, tutorial Who loves ya. Tom Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://pages.ivillage.com/ironjustice/manisaherbivore DEAD PEOPLE WALKING http://pages.ivillage.com/ironjustice/deadpeoplewalking > Since the PROBLEM with the anti-psychotics IS the .. buildup of iron .. > then one might think the 'novel brain-targeted antioxidant ' .. might > be an iron .. chelator. anti-psychotics??? Preaching to the choir? Gee, I bet all the psychotics in these ngs with thank you forever. :( Ha, ... Hah, Ha!!! Are there any NON-kooks on these ngs? ironjustice@aol.com wrote: > Since the PROBLEM with the anti-psychotics IS the .. buildup of iron .. > then one might think the 'novel brain-targeted antioxidant ' .. might > be an iron .. chelator. anti-psychotics??? Preaching to the choir? Gee, I bet all the psychotics in these ngs will thank you forever. :( Ha, ... Hah, Ha!!! Are there any NON-kooks on these ngs? > ironjustice@aol.com wrote: >> Since the PROBLEM with the anti-psychotics IS the .. buildup of iron .. [quoted text clipped - 10 lines] > > Are there any NON-kooks on these ngs? Don't you hate it with you make those kind of mistakes? Neuroleptics are commonly called "anti-psychotics." Did I miss a spelling error? > > ironjustice@aol.com wrote: > >> Since the PROBLEM with the anti-psychotics IS the .. buildup of iron .. [quoted text clipped - 12 lines] > > Don't you hate it with you make those kind of mistakes?
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