RTI-336

Chemical compound From Wikipedia, the free encyclopedia

RTI-336, also known as RTI-4229-336 or LS-193,309 is a potent and selective dopamine reuptake inhibitor that was initially developed by the Research Triangle Institute, now known as RTI International.[1]

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RTI-336
Identifiers
  • 5-[(1S,3S,4S,5R)-3-(4-Chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octan-4-yl]-3-(4-methylphenyl)-1,2-oxazole
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Chemical and physical data
FormulaC24H25ClN2O
Molar mass392.93 g·mol−1
3D model (JSmol)
  • CC1=CC=C(C=C1)C2=NOC(=C2)[C@@H]3[C@H]4CC[C@H](N4C)C[C@@H]3C5=CC=C(C=C5)
  • InChI=1S/C24H25ClN2O/c1-15-3-5-17(6-4-15)21-14-23(28-26-21)24-20(16-7-9-18(25)10-8-16)13-19-11-12-22(24)27(19)2/h3-10,14,19-20,22,24H,11-13H2,1-2H3/t19-,20+,22+,24-/m0/s1
  • Key:AUXUFNHAVGIVDC-IKJKNFHUSA-N
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Pharmacology

It is a phenyltropane derivative that binds to the dopamine transporter with approximately 20 times the affinity of cocaine.[2] However, it produces relatively mild stimulant effects, with a slow onset and a long duration of action.[3] (Although, other sources classify it as having among the faster onsets of action among phenyltropanes.[4])

Affinity of RIT-336 and analogs for the main monoamine transporters (DAT, NET, SERT):[1]

More information X, R ...
RTIXR[3H]CFT[3H]Nisoxetine[3H]ParoxetineN ÷ DS ÷ D
Coc——89.13298 (1986)1045 (45)37.0111.79
177Clphenyl1.28504 (304)2420 (220)393.81891
176Mephenyl1.58398 (239)5110 (465)251.93234
354Meethyl1.62299 (180)6400 (582)184.63951
336Clp-tolyl4.091714 (1033)5741 (522)419.11404
386Mep-anisyl3.93756 (450)4027 (380)192.41025
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  • [3H]CFT: [3H]CFT is a selective radioligand for the dopamine transporter (DAT)
  • [3H]Nisoxetine: This is a radioligand for the norepinephrine transporter (NET)
  • [3H]Paroxetine: This is a radioligand for the serotonin transporter (SERT)
  • N ÷ D: ratio of norepinephrine transporter (NET) affinity to dopamine transporter (DAT) affinity
  • S ÷ D: ratio of serotonin transporter (SERT) affinity to dopamine transporter (DAT) affinity

Animal studies

These characteristics make it a potential candidate for the treatment of cocaine addiction, as a possible substitute drug, analogous to the use of methadone for treating heroin dependence.[1][5] RTI-336 fully substitutes for cocaine in addicted monkeys and supports self-administration,[4][6] and significantly reduces rates of cocaine use, especially when combined with SSRIs.[7] Research is ongoing to determine whether it could be a viable substitute drug in human cocaine addicts.

RTI-336 and RTI-177 exhibited lower reinforcing strength than cocaine in nonhuman primates, indicating reduced abuse liability and supporting their viability as pharmacotherapies for addiction.[8]

Chronic RTI-336 administration in rhesus monkeys altered motor activity and sleep patterns but did not cause adverse hormonal changes, suggesting a relatively safe profile for long-term therapeutic use.[9]

Clinical studies

A dosage of up to 20mg has been tolerated in healthy males.[10]

See also

References

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