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Vanoxerine
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| Systematic (IUPAC) name | |
| 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine | |
| Identifiers | |
| CAS number | |
| ATC code | ? |
| PubChem | |
| Chemical data | |
| Formula | C28H33F2N2O |
| Mol. mass | 450.563 g/mol (freebase); 523.494 g/mol (dihydrochloride) |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | 6 hours approx |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
? |
| Legal status |
Investigational New Medicine |
| Routes | ? |
Vanoxerine, also known as GBR-12909, is a piperazine derivative which is a potent and selective dopamine reuptake inhibitor. GBR-12909 binds to the target site on the dopamine reuptake transporter around 500 times more strongly than cocaine, but simultaneously inhibits the release of dopamine. This combined effect only slightly elevates dopamine levels, giving vanoxerine only mild stimulant effects.1
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.23
Research also indicates that vanoxerine may have additional mechanisms of action including antagonist action at nicotinic acetylcholine receptors,4 and it has also been shown to reduce the consumption of alcohol in animal models of alcohol abuse.5
Vanoxerine has been through human trials up to Phase II,678 but development was halted after it was shown to cause long QT syndrome.9
A decanoate ester of vanoxerine, DBL-583, has also been developed, which slowly breaks down in the body and lasts for up to a month after a single injection.1011
References
- ^ Singh S. Chemistry, Design, and Structure-Activity Relationship of Cocaine Antagonists. Chemistry Reviews, 2000. 100(3): 925-1024.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ Søgaard U, Michalow J, Butler B, et al (1990). "A tolerance study of single and multiple dosing of the selective dopamine uptake inhibitor GBR 12909 in healthy subjects". International clinical psychopharmacology 5 (4): 237–51. PMID 2150527.
- ^ 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.
- ^ 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.
- ^ Baumann MH, Ayestas MA, Sharpe LG, Lewis DB, Rice KC, Rothman RB. Persistent antagonism of methamphetamine-induced dopamine release in rats pretreated with GBR12909 decanoate. Journal of Pharmacology and Experimental Therapeutics. 2002 Jun;301(3):1190-7.
- ^ Baumann MH, Phillips JM, Ayestas MA, Ali SF, Rice KC, Rothman RB. Preclinical evaluation of GBR12909 decanoate as a long-acting medication for methamphetamine dependence. Annals of the New York Academy of Sciences. 2002 Jun;965:92-108.
Wikipedia content modification information:
- This page was last modified on 30 October 2008, at 21:04.
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