(-)-2β-(3-(4-Methylphenyl)isoxazol-5-yl)-3β-(4-chlorophenyl)tropane
Wikipedia on Answers.com:
Top
(-)-2β-(3-(4-Methylphenyl)isoxazol-5-yl)-3β-(4-chlorophenyl)tropane
 |
|
|---|---|
| Systematic (IUPAC) name | |
| (1R,2S,3S,5S)-8-methyl-2-(3-(4-methylphenyl)isoxazol-5-yl)-3-(4-chlorophenyl)-8-azabicyclo[3.2.1]octane | |
| Clinical data | |
| Pregnancy cat. | ? |
| Legal status | ? |
| Identifiers | |
| ATC code | ? |
| PubChem | CID 9800708 |
| Chemical data | |
| Formula | C24H25ClN2O |
| Mol. mass | 392.920 |
| SMILES | eMolecules & PubChem |
RTI-336, (LS-193,309, (-)-2β-(3-(4-methylphenyl)isoxazol-5-yl)-3β-(4-chlorophenyl)tropane) is a phenyltropane derivative which acts as a potent and selective dopamine reuptake inhibitor and stimulant drug. It binds to the dopamine transporter with around 20x the affinity of cocaine,[1] however it produces relatively mild stimulant effects, with a slow onset and long duration of action.[2] These characteristics make it a potential candidate for treatment of cocaine addiction, as a possible substitute drug analogous to how methadone is used for treating heroin abuse.[3][4] RTI-336 fully substitutes for cocaine in addicted monkeys and supports self-administration,[5][6] and significantly reduces rates of cocaine use, especially when combined with SSRIs,[7] and research is ongoing to determine whether it could be a viable substitute drug in human cocaine addicts.
|
Contents
|
Update
Pharmacotherapy for Cocaine Abuse
| RTI | X | R | [3H]CFT | [3H]Nisoxetine | [3H]Paroxetine | N ÷ D | S ÷ D |
|---|---|---|---|---|---|---|---|
| Coc | — | — | 89.1 | 3298 (1986) | 1045 (45) | 37.01 | 11.79 |
| 177 | Cl | phenyl | 1.28 | 504 (304) | 2420 (220) | 393.8 | 1891 |
| 176 | Me | phenyl | 1.58 | 398 (239) | 5110 (465) | 251.9 | 3234 |
| 354 | Me | ethyl | 1.62 | 299 (180) | 6400 (582) | 184.6 | 3951 |
| 336 | Cl | p-cresyl | 4.09 | 1714 (1033) | 5741 (522) | 419.1 | 1404 |
| 386 | Me | p-anisyl | 3.93 | 756 (450) | 4027 (380) | 192.4 | 1025 |
See also
References
- ^ Carroll, F.; Pawlush, N.; Kuhar, M.; Pollard, G.; Howard, J. (2004). "Synthesis, monoamine transporter binding properties, and behavioral pharmacology of a series of 3beta-(substituted phenyl)-2beta-(3'-substituted isoxazol-5-yl)tropanes". Journal of Medicinal Chemistry 47 (2): 296–302. doi:10.1021/jm030453p. PMID 14711303.
- ^ Carroll, F.; Fox, B.; Kuhar, M.; Howard, J.; Pollard, G.; Schenk, S. (2006). "Effects of dopamine transporter selective 3-phenyltropane analogs on locomotor activity, drug discrimination, and cocaine self-administration after oral administration". European Journal of Pharmacology 553 (1–3): 149–156. doi:10.1016/j.ejphar.2006.09.024. PMID 17067572.
- ^ Carroll, F.; Howard, J.; Howell, L.; Fox, B.; Kuhar, M. (2006). "Development of the dopamine transporter selective RTI-336 as a pharmacotherapy for cocaine abuse". The AAPS journal 8 (1): E196–E203. doi:10.1208/aapsj080124. PMC 2751440. PMID 16584128. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2751440.
- ^ Sofuoglu M, Kosten TR. Emerging pharmacological strategies in the fight against cocaine addiction. Expert Opinion on Emerging Drugs. 2006 Mar;11(1):91-98. doi:10.1517/14728214.11.1.91
- ^ Kimmel, H. .; O'Connor, J. .; Carroll, F. .; Howell, L. . (2007). "Faster onset and dopamine transporter selectivity predict stimulant and reinforcing effects of cocaine analogs in squirrel monkeys". Pharmacology, Biochemistry, and Behavior 86 (1): 45–54. doi:10.1016/j.pbb.2006.12.006. PMC 1850383. PMID 17258302. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1850383.
- ^ Kimmel, H.; Negus, S.; Wilcox, K.; Ewing, S.; Stehouwer, J.; Goodman, M.; Votaw, J.; Mello, N. et al (2008). "Relationship between rate of drug uptake in brain and behavioral pharmacology of monoamine transporter inhibitors in rhesus monkeys". Pharmacology, Biochemistry, and Behavior 90 (3): 453–462. doi:10.1016/j.pbb.2008.03.032. PMC 2453312. PMID 18468667. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2453312.
- ^ Howell, L.; Carroll, F.; Votaw, J.; Goodman, M.; Kimmel, H. (2007). "Effects of combined dopamine and serotonin transporter inhibitors on cocaine self-administration in rhesus monkeys". The Journal of Pharmacology and Experimental Therapeutics 320 (2): 757–765. doi:10.1124/jpet.106.108324. PMID 17105829.
- ^ Navarro, H.; Howard, J.; Pollard, G.; Carroll, F. (2009). "Positive allosteric modulation of the human cannabinoid (CB1) receptor by RTI-371, a selective inhibitor of the dopamine transporter". British Journal of Pharmacology 156 (7): 1178–1184. doi:10.1111/j.1476-5381.2009.00124.x. PMC 2697692. PMID 19226282. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2697692.
|
|||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
This drug article relating to the nervous system is a stub. You can help Wikipedia by expanding it. |
This entry is from Wikipedia, the leading user-contributed encyclopedia. It may not have been reviewed by professional editors (see full disclaimer)
Post a question - any question - to the WikiAnswers community:
Copyrights:
Wikipedia on Answers.com
This article is licensed under the Creative Commons Attribution/Share-Alike License. It uses material from the Wikipedia article (-)-2β-(3-(4-Methylphenyl)isoxazol-5-yl)-3β-(4-chlorophenyl)tropane.
Read more