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Vanoxerine (GBR-12909) is a piperazine derivative which is a potent and selective dopamine reuptake inhibitor (DRI). GBR-12909 binds to the target site on the dopamine transporter (DAT) ~ 50 times more strongly than cocaine,according to the article at http://www.ncbi.nlm.nih.gov/pubmed/2145054 == Vanoxerine as a treatment for cocaine dependence == Vanoxerine has been researched for use in treating cocaine dependence both as a substitute for cocaine and to block the rewarding effects. This strategy of using a competing agonist with a longer half-life has been successfully used to treat addiction to opiates such as heroin by substituting with methadone. It was hoped that vanoxerine would be of similar use in treating cocaine addiction.〔Vetulani J. Drug addiction. Part III. Pharmacotherapy of addiction. ''Polish Journal of Pharmacology''. 2001 Sep-Oct;53(5):415-34.〕〔Preti A. New developments in the pharmacotherapy of cocaine abuse. ''Addiction Biology''. 2007 Jun;12(2):133-51.〕 Research also indicates that vanoxerine may have additional mechanisms of action including antagonist action at nicotinic acetylcholine receptors,〔Szasz BK, Vizi ES, Kiss JP. Nicotinic acetylcholine receptor antagonistic property of the selective dopamine uptake inhibitor, GBR-12909 in rat hippocampal slices. ''Neuroscience''. 2007 Mar 2;145(1):344-9.〕 and it has also been shown to reduce the consumption of alcohol in animal models of alcohol abuse.〔Kamdar NK, Miller SA, Syed YM, Bhayana R, Gupta T, Rhodes JS. Acute effects of naltrexone and GBR 12909 on ethanol drinking-in-the-dark in C57BL/6J mice. ''Psychopharmacology (Berlin)''. 2007 Jun;192(2):207-17.〕 Vanoxerine has been through human trials up to Phase II,〔Preti A. Vanoxerine National Institute on Drug Abuse. ''Current Opinion in Investigational Drugs''. 2000 Oct;1(2):241-51.〕〔Gorelick DA, Gardner EL, Xi ZX. Agents in development for the management of cocaine abuse. ''Drugs''. 2004;64(14):1547-73.〕 but development was stopped due to observed QTc effects in the context of cocaine use.〔Herman BH, Elkashef A, Vocci F. Medications for the treatment of cocaine addiction: Emerging candidates. ''Drug Discovery Today: Therapeutic Strategies''. 2005 Spring;2(1):87-92.〕 However, GBR 12909 analogs continue to be studied as treatments for cocaine addiction. As an example, GBR compounds are piperazine based and contain a proximal and a distal nitrogen. It was found that piperidine analogs are still fully active DRIs, although they do not have any affinity for the "piperazine binding site" unlike the GBR compounds. Further SAR revealed that while there are 4 atoms connecting the two fluorophenyl rings to the piperazine, the ether in the chain could be omitted in exchange for a tertiary nitrogen. Vanoxerine, a blocker of the dopamine carrier devoid of action on the noradrenaline carrier, while fully increasing dopamine in the nucleus accumbens, is ineffective in raising extracellular dopamine in the prefrontal cortex. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Vanoxerine」の詳細全文を読む スポンサード リンク
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