RTI-112

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RTI-112
Identifiers
  • Methyl (1R,2S,3S,5S)-3-(4-chloro-3-methylphenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
JSmol)
  • CC1=C(C=CC(=C1)[C@H]2C[C@@H]3CC[C@H]([C@H]2C(=O)OC)N3C)Cl
  • InChI=1S/C17H22ClNO2/c1-10-8-11(4-6-14(10)18)13-9-12-5-7-15(19(12)2)16(13)17(20)21-3/h4,6,8,12-13,15-16H,5,7,9H2,1-3H3/t12-,13+,15+,16-/m0/s1 ☒N
  • Key:VMITZEMDDZVHBZ-XNISGKROSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

RTI(-4229)-112 (2β-carbomethoxy-3β-(3-methyl-4-chlorophenyl)tropane) is a synthetic

triple reuptake inhibitor.[1]

In vitro tests show a very similar serotonin transporter (SERT)/dopamine transporter (DAT)/norepinephrine transporter (NET) selectivity to cocaine,[2] although in vivo behaviour is different:

"The nonselective monoamine transporter inhibitor RTI-126 and the DAT-selective inhibitors RTI-150 and RTI-336 both had a faster rate of onset (30 min) and a short duration of action (4h). In contrast, the nonselective monoamine transporter inhibitor RTI-112 had a slower rate of onset (30–60 min) and a longer duration of action (10h). The DAT-selective inhibitors RTI-171 and RTI-177 also had slower rates of onset (30–120 min), but RTI-171 had a short duration of action (2.5 h) while RTI-177 had a very long duration of action (20 h)."[3]

The efficacy of cocaine analogs to elicit self-administration is related to the rate at which they are administered.[clarification needed] Slower onset analogs are less likely to function as behavioral stimulants than analogs eliciting a faster rate of onset.[4] Nonselective analogs are less likely to function as "reinforcers" than reuptake inhibitors that have DAT specificity.[3]

In order for a

PET scans on primates reveal that the DAT occupancy needs to be >60%.[5]

RTI-112 has equipotent in vitro affinity at the SERT, NET and DAT, respectively.[2] RTI-112 was not reliably self-administered, in contrast to the DAT selective reuptake inhibitors that were used in this study.[2]

In vivo at the ED50, RTI-112 had no DAT occupancy at all.[2] At the ED50, almost all of the RTI-112 occupied the SERT at this dose.[2] A significantly higher dose was required to get >70% DAT occupancy in the case of RTI-112;[2] however, RTI-112 was still able to suppress cocaine administration at the ED50, suggesting a serotonergic mechanism was responsible for this.[2]

References

  1. S2CID 10004289. Archived from the original
    (PDF) on 2010-06-11.
  2. ^
    S2CID 39794215. Archived from the original
    (PDF) on 2010-06-11. Retrieved 2009-07-15.
  3. ^
    PMID 17258302
    .
  4. PMID 15957006
    .
  5. PMID 11408518. Archived from the original
    (PDF) on 2006-09-21.
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