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Rti-386 Information

RTI-177 (2β-(3-phenylisoxazol-5-yl)-3β-(4-chlorophenyl)tropane, β-CPPIT) is a synthetic stimulant drug from the phenyltropane family, which acts as a DRI with micromolar affinity for the SERT.[1] RTI-177 has an unusually long duration of action of 20 hours or more, substantially longer than the related compound RTI-336 from which it differs in molecular structure only by the absence of a p-methyl group.[2]

"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]

Comparison of six MAT inhibitors

RTI X R [3H]CFT [3H]Nisoxetine [3H]Paroxetine
Coc 89.1 3298 (1986) 1045 (45)
177 Cl phenyl 1.28 504 (304) 2420 (220)
176 Me phenyl 1.58 398 (239) 5110 (465)
354 Me ethyl 1.62 299 (180) 6400 (582)
336 Cl p-cresyl 4.09 1714 (1033) 5741 (522)
386 Me p-anisoyl 3.93 756 (450) 4027 (380)

In the Lindsey paper, RTI-177 was wrongly considered to be a dual inhibitor of the NET, although this was later found out to be incorrect (despite being written in plain English).

"In acute toxicity studies in male rats, 3β-(4-chlorophenyl)-2β-[3-(4’-methylphenyl)isoxazol-5-yl]tropane (RTI-336) possessed an LD50 of 180 mg/kg after oral administration, compared with 49 mg/kg for RTI-177 (unpublished results, Howell 2005; Table 9). These results suggested that RTI-336 was a better candidate than RTI-177 for further preclinical development."[2]

Also the potency of the heterocyclic compounds is not as great as would be predicted based on in vitro test results.

References

  1. ^ [1] Lindsey, K.P., Wilcox, K.M., Votaw, J.R., Goodman, M.M., Plisson, C., Carroll, F.I., Rice, K.C., Howell, L.L. Effects of dopamine transporter inhibitors on cocaine self-administration in rhesus monkeys: relationship to transporter occupancy determined by positron emission tomography neuroimaging. Journal of Pharmacology and Experimental Therapeutics, 309: 959-969, 2004.
  2. ^ a b [2] Carroll FI, Howard JL, Howell LL, Fox BS, Kuhar MJ. Development of the dopamine transporter selective RTI-336 as a pharmacotherapy for cocaine abuse. AAPS J. 2006 Mar 24;8(1):E196-203.
  3. ^ [3] Kimmel HL, O'Connor JA, Carroll FI, Howell LL. Faster onset and dopamine transporter selectivity predict stimulant and reinforcing effects of cocaine analogs in squirrel monkeys. Pharmacol Biochem Behav. 2007 Jan;86(1):45-54.
Phenyltropanes (classifications)
2-Carboxymethyl Esters

TroparilWIN 35428RTI-31RTI-32RTI-51RTI-55RTI-83

(3,4-Disubstituted Phenyl)-tropanes

DichloropaneRTI-112RTI-353

Arylcarboxy

RTI-113RTI-120

Carboxyalkyl

RTI-121RTI-150

Acyl

PTT/WF-11WF-23PIT/WF-21WF-33

β,α Stereochemistry

RTI-352RTI-274

α,β Stereochemistry

BrasofensineTesofensineNS2359

Heterocycles: 3-Substituted-isoxazol-5-yl

RTI-177RTI-336RTI-371

Heterocycles: 3-Substituted-1,2,4-oxadiazole

RTI-126RTI-371

N-alkyl

FP-β-CPPITFE-β-CPPITAltropaneIoflupane (123I)

N-replaced (S,O,C)

Tropoxane

Irreversible

RTI-76

Nortropanes (N-demethylated)

NS2359 (GSK-372,475)

Stimulants (N06B)
Adamantanes

Adaphenoxate • Adapromine • AmantadineBromantane • Chlodantane • Gludantane • Memantine • Midantane

Adenosine antagonists 8-Chlorotheophylline8-Cyclopentyltheophylline8-PhenyltheophyllineAminophyllineCaffeineCGS-15943DimethazanParaxanthineSCH-58261TheobromineTheophylline
Alkylamines

CyclopentamineCypenamineCyprodenateHeptaminolIsomethepteneMethylhexaneamineOctodrinePropylhexedrineTuaminoheptane

Arylcyclohexylamines

BenocyclidineDieticyclidineEsketamineEticyclidineGacyclidineKetamine • Phencyclamine • PhencyclidineRolicyclidineTenocyclidineTiletamine

Benzazepines

6-Br-APBSKF-77434SKF-81297SKF-82958

Cholinergics

A-84543A-366,833ABT-202 • ABT-418 • AR-R17779AltiniclineAnabasineArecolineCotinineCytisineDianiclineEpibatidineEpiboxidineGTS-21IsproniclineNicotinePHA-543,613PNU-120,596PNU-282,987PozaniclineRivaniclineSazetidine ASIB-1553A • SSR-180,711 • TC-1698 • TC-1827 • TC-2216TC-5619TebaniclineUB-165VareniclineWAY-317,538

Convulsants

Anatoxin-aBicucullineDMCMFlurothylGabazinePentetrazolPicrotoxinStrychnineThujone

Eugeroics

AdrafinilArmodafinilCRL-40941Modafinil

Oxazolines

4-MethylaminorexAminorexClominorexCyclazodoneFenozoloneFluminorexPemolineThozalinone

Phenethylamines

1-(4-Methylphenyl)-2-aminobutane • 1-Phenyl-2-(piperidin-1-yl)pentan-3-one • 1-Methylamino-1-(3,4-methylenedioxyphenyl)propane2-Fluoroamphetamine2-Fluoromethamphetamine2-OH-PEA • 2-Phenyl-3-aminobutane • 2-Phenyl-3-methylaminobutane • 2,3-MDA3-Fluoroamphetamine3-Fluoroethamphetamine3-Fluoromethcathinone3-Methoxyamphetamine3-Methylamphetamine3,4-DMMC4-BMC4-Ethylamphetamine4-FA4-FMA4-MA4-MMA4-MTA6-FNEAlfetamineα-EthylphenethylamineAmfecloralAmfepentorexAmfepramoneAmidephrineAmphetamine (Dextroamphetamine, Levoamphetamine) • AmphetaminilArbutamineβ-Methylphenethylamineβ-PhenylmethamphetamineBenfluorexBenzedroneBenzphetamineBDB (J) • BOH (Hydroxy-J) • BPAPBuphedroneBupropion (Amfebutamone) • ButyloneCathineCathinoneChlorphentermine • Cinnamedrine • ClenbuterolClobenzorexCloforexClortermineD-DeprenylDenopamineDimethoxyamphetamineDimethylamphetamineDimethylcathinone (Dimethylpropion, Metamfepramone) • DobutamineDOPA (Dextrodopa, Levodopa) • DopamineDopexamineDroxidopaEBDB (Ethyl-J) • EphedrineEpinephrine (Adrenaline) • Epinine (Deoxyepinephrine) • EtafedrineEthcathinone (Ethylpropion) • Ethylamphetamine (Etilamfetamine) • Ethylnorepinephrine (Butanefrine) • EthyloneEtilefrineFamprofazoneFenbutrazateFencamineFenethyllineFenfluramine (Dexfenfluramine) • FenmetramideFenproporexFlephedroneFludorexFurfenorexGepefrine • HMMA • HordenineIbopamineIMPIndanylamphetamineIsoetarineIsoethcathinoneIsoprenaline (Isoproterenol) • L-Deprenyl (Selegiline) • LefetamineLisdexamfetamineLophophine (Homomyristicylamine) • ManifaxineMBDB (Methyl-J; "Eden") • MDA (Tenamfetamine) • MDBUMDEA ("Eve") • MDMA ("Ecstasy", "Adam") • MDMPEA (Homarylamine) • MDOHMDPRMDPEA (Homopiperonylamine) • MefenorexMephedroneMephentermineMetanephrineMetaraminol • Methamphetamine (Desoxyephedrine, Methedrine; Dextromethamphetamine, Levomethamphetamine) • MethoxamineMethoxyphenamineMMAMethcathinone (Methylpropion) • MethedroneMethoxyphenamineMethyloneMMDAMMDMAMMMAMorazone • N-Benzyl-1-phenethylamine • N,N-Dimethylphenethylamine • NaphthylamphetamineNisoxetineNorepinephrine (Noradrenaline) • NorfenefrineNorfenfluramineNormetanephrineOctopamineOrciprenalineOrtetamineOxilofrineParedrine (Norpholedrine, Oxamphetamine, Mycadrine) • PBAPCAPHAPargylinePentorex (Phenpentermine) • PentylonePhenatinePhendimetrazinePhenmetrazinePhenpromethaminePhenterminePhenylalaninePhenylephrine (Neosynephrine) • PhenylpropanolaminePholedrinePIAPMAPMEAPMMAPPAPPrenylaminePropylamphetaminePseudoephedrineRadafaxineRopiniroleSalbutamol (Albuterol; Levosalbutamol) • SibutramineSynephrine (Oxedrine) • TheodrenalineTiflorex (Flutiorex) • TranylcypromineTyramineTyrosineXamoterolXylopropamineZylofuramine

Piperazines

2C-B-BZPBZP • CM156 • DBL-583 • GBR-12783 • GBR-12935 • GBR-13069 • GBR-13098 • GBR-13119 • MeOPPMBZPVanoxerine

Piperidines

1-Benzyl-4-(2-(diphenylmethoxy)ethyl)piperidine • 1-(3,4-Dichlorophenyl)-1-(piperidin-2-yl)butane • 2-Benzylpiperidine • 2-Methyl-3-phenylpiperidine • 3,4-Dichloromethylphenidate4-Benzylpiperidine4-MethylmethylphenidateDesoxypipradrolDifemetorexDiphenylpyralineEthylphenidateMethylnaphthidateMethylphenidate (Dexmethylphenidate) • N-Methyl-3β-propyl-4β-(4-chlorophenyl)piperidine • NocainePhacetoperanePipradrolSCH-5472

Pyrrolidines

2-Diphenylmethylpyrrolidineα-PPPα-PBPα-PVPDiphenylprolinolMDPPPMDPBPMDPVMPBPMPHPMPPPMOPPPNaphyronePEPProlintanePyrovalerone

Tropanes

3-CPMT • 3'-Chloro-3α-(diphenylmethoxy)tropane • 3-Pseudotropyl-4-fluorobenzoate4'-Fluorococaine • AHN-1055 • Altropane (IACFT)BrasofensineCFT (WIN 35,428)β-CIT (RTI-55)CocaethyleneCocaineDichloropane (RTI-111)DifluoropineFE-β-CPPITFP-β-CPPITIoflupane (123I)NorcocainePITPTTRTI-31RTI-32RTI-51 • RTI-105 • RTI-112RTI-113 • RTI-117 • RTI-120RTI-121 (IPCIT)RTI-126RTI-150 • RTI-154 • RTI-171 • RTI-177 • RTI-183 • RTI-193 • RTI-194 • RTI-199 • RTI-202 • RTI-204 • RTI-229 • RTI-241 • RTI-336RTI-354RTI-371RTI-386SalicylmethylecgonineTesofensineTroparil (β-CPT, WIN 35,065-2)TropoxaneWF-23WF-33 • WF-60

Others

1-(Thiophen-2-yl)-2-aminopropane2-Amino-1,2-dihydronaphthalene2-Aminoindane2-Aminotetralin2-MDP • 2-Phenylcyclohexylamine • 2-Phenyl-3,6-dimethylmorpholine3-Benzhydrylmorpholine3,3-Diphenylcyclobutanamine5-(2-Aminopropyl)indole5-Iodo-2-aminoindaneAL-1095Amfonelic acidAmineptineAmiphenazoleAtipamezoleAtomoxetine (Tomoxetine) • BemegrideBenzydamineBTQBTS 74,398CamfetamineCarphedonCiclazindolCilobamineClofenciclan • Cropropamide • Crotetamide • CypenamineD-161DiclofensineDimethocaineEfaroxanEtamivanEXP-561FencamfamineFenpentadiolFeprosidnineG-130GamfexineGilutensinGSK1360707FGYKI-52895HexacyclonateIdazoxanIndanorexIndatralineJNJ-7925476JZ-IV-10Lazabemide • Leptacline • LevopropylhexedrineLomevactone • LR-5182 • MazindolMeclofenoxateMedifoxamine • Mefexamide • MesocarbMethastyridoneMethiopropamine • N-Methyl-3-phenylnorbornan-2-amine • NefopamNikethamideNomifensineO-2172OxaprotilinePhthalimidopropiophenonePNU-99,194PropylhexedrinePRC200-SSRasagilineRauwolscineRubidium chlorideSetazindolTametralineTandamineTraziumUH-232Yohimbine

See also
Dopaminergics
Receptor ligands
Agonists Adamantanes: AmantadineMemantineRimantadine; Aminotetralins: 7-OH-DPAT8-OH-PBZIRotigotineUH-232; Benzazepines: 6-Br-APBFenoldopamSKF-38,393SKF-77,434SKF-81,297SKF-82,958SKF-83,959; Ergolines: BromocriptineCabergolineDihydroergocryptineLisurideLSDPergolide; Dihydrexidine derivatives: 2-OH-NPAA-86,929CiladopaDihydrexidineDinapsolineDinoxylineDoxanthrine; Others: A-68,930A-77636A-412,997ABT-670ABT-724AplindoreApomorphineAripiprazoleBifeprunoxBP-897CY-208,243DizocilpineEtilevodopaFlibanserinKetamineMelevodopaModafinilPardoprunoxPhencyclidinePD-128,907PD-168,077PF-219,061PiribedilPramipexolePropylnorapomorphinePukateineQuinagolideQuineloraneQuinpiroleRDS-127Ro10-5824RopiniroleRotigotineRoxindoleSalvinorin ASKF-89,145SumaniroleTergurideUmespironeWAY-100,635
Antagonists Typical antipsychotics: AcepromazineAzaperoneBenperidolBromperidolClopenthixolChlorpromazineChlorprothixeneDroperidolFlupentixolFluphenazineFluspirileneHaloperidolLoxapineMesoridazineMethotrimeprazineNemonapridePenfluridolPerazinePericiazinePerphenazinePimozideProchlorperazinePromazineSulforidazineSulpirideSultoprideThioridazineThiothixeneTrifluoperazineTriflupromazineTrifluperidolZuclopenthixol; Atypical antipsychotics: AmisulprideAsenapineBlonanserinCariprazineCarpipramineClocapramineClorotepineClozapineGevotrolineIloperidoneLurasidoneMelperoneMolindoneMosapramineOlanzapinePaliperidonePerospironePiquindoneQuetiapineRemoxiprideRisperidoneSertindoleTiospironeZiprasidoneZotepine; Antiemetics: AS-8112AlizaprideBromoprideCleboprideDomperidoneMetoclopramideThiethylperazine; Others: AmoxapineBuspironeButaclamolEcopipamEEDQEticloprideFananserinL-745,870NafadotrideNuciferinePNU-99,194RacloprideSarizotanSB-277,011-ASCH-23,390SKF-83,959SonepiprazoleSpiperoneSpiroxatrineStepholidineTetrahydropalmatineTiaprideUH-232Yohimbine
Reuptake inhibitors
Plasmalemmal
DAT inhibitors Piperazines: DBL-583GBR-12,935NefazodoneVanoxerine; Piperidines: BTCPDesoxypipradrolDextromethylphenidateDifemetorexEthylphenidateMethylnaphthidateMethylphenidatePhencyclidinePipradrol; Pyrrolidines: DiphenylprolinolMethylenedioxypyrovalerone (MDPV) • NaphyroneProlintanePyrovalerone; Tropanes: β-CPPITAltropaneBrasofensineCFTCocaineDichloropaneDifluoropineFE-β-CPPITFP-β-CPPITIoflupane (123I)IometopaneRTI-112RTI-113RTI-121RTI-126RTI-150RTI-177RTI-229RTI-336TenocyclidineTesofensineTroparilTropoxaneWF-11WF-23WF-31WF-33; Others: AdrafinilArmodafinilAmfonelic acidAmineptineBenzatropine (Benztropine) • BromantaneBTQBTS-74,398Bupropion (Amfebutamone) • CiclazindolDiclofensineDimethocaineDiphenylpyralineDizocilpineDOV-102,677DOV-21,947DOV-216,303Etybenzatropine (Ethylbenztropine) • EXP-561FencamineFencamfamineFezolamineGYKI-52,895IndatralineKetamineLefetamineLevophacetoperane • LR-5182 • ManifaxineMazindolMedifoxamineMesocarbModafinilNefopamNomifensineNS-2359O-2172PridefrinePropylamphetamineRadafaxineSEP-225,289SEP-227,162SertralineSibutramineTametralineTedatioxetineTripelennamine
Vesicular
VMAT inhibitors DeserpidineIbogaineReserpineTetrabenazine
Releasing agents
Morpholines: FenbutrazateMorazonePhendimetrazinePhenmetrazine; Oxazolines: 4-Methylaminorex (4-MAR, 4-MAX) • AminorexClominorexCyclazodoneFenozoloneFluminorexPemolineThozalinone; Phenethylamines (also amphetamines, cathinones, phentermines, etc): 2-Hydroxyphenethylamine (2-OH-PEA) • 4-CAB4-Methylamphetamine (4-MA) • 4-Methylmethamphetamine (4-MMA) • AlfetamineAmfecloralAmfepentorexAmfepramoneAmphetamine (Dextroamphetamine, Levoamphetamine) • Amphetaminilβ-Methylphenethylamine (β-Me-PEA) • Benzodioxolylbutanamine (BDB) • Benzodioxolylhydroxybutanamine (BOH) • BenzphetamineBuphedroneButyloneCathineCathinoneClobenzorexClortermineD-DeprenylDimethoxyamphetamine (DMA) • Dimethoxymethamphetamine (DMMA) • DimethylamphetamineDimethylcathinone (Dimethylpropion, metamfepramone) • Ethcathinone (Ethylpropion) • EthylamphetamineEthylbenzodioxolylbutanamine (EBDB) • EthyloneFamprofazoneFenethyllineFenproporexFlephedroneFludorexFurfenorexHordenineLophophine (Homomyristicylamine) • MefenorexMephedrone • Methamphetamine (Desoxyephedrine, Methedrine; Dextromethamphetamine, Levomethamphetamine) • Methcathinone (Methylpropion) • MethedroneMethoxymethylenedioxyamphetamine (MMDA) • Methoxymethylenedioxymethamphetamine (MMDMA) • Methylbenzodioxolylbutanamine (MBDB) • Methylenedioxyamphetamine (MDA, tenamfetamine) • Methylenedioxyethylamphetamine (MDEA) • Methylenedioxyhydroxyamphetamine (MDOH) • Methylenedioxymethamphetamine (MDMA) • Methylenedioxymethylphenethylamine (MDMPEA, homarylamine) • Methylenedioxyphenethylamine (MDPEA, homopiperonylamine) • MethyloneOrtetamineParabromoamphetamine (PBA) • Parachloroamphetamine (PCA) • Parafluoroamphetamine (PFA) • Parafluoromethamphetamine (PFMA) • Parahydroxyamphetamine (PHA) • Paraiodoamphetamine (PIA) • Paredrine (Norpholedrine, Oxamphetamine) • Phenethylamine (PEA) • PholedrinePhenpromethaminePrenylaminePropylamphetamineTiflorex (Flutiorex) • Tyramine (TRA) • XylopropamineZylofuramine; Piperazines: 2,5-Dimethoxy-4-bromobenzylpiperazine (2C-B-BZP) • Benzylpiperazine (BZP) • Methoxyphenylpiperazine (MeOPP, paraperazine) • Methylbenzylpiperazine (MBZP) • Methylenedioxybenzylpiperazine (MDBZP, piperonylpiperazine); Others: 2-Amino-1,2-dihydronaphthalene (2-ADN) • 2-Aminoindane (2-AI) • 2-Aminotetralin (2-AT) • 4-Benzylpiperidine (4-BP) • 5-IAIClofenciclanCyclopentamineCypenamineCyprodenateFeprosidnineGilutensinHeptaminolHexacyclonateIndanylaminopropane (IAP) • IndanorexIsomethepteneMethylhexanamineNaphthylaminopropane (NAP) • OctodrinePhthalimidopropiophenonePropylhexedrine (Levopropylhexedrine) • Tuaminoheptane (Tuamine)
Allosteric modulators
Quinazolinamines: SoRI-9804 • SoRI-20040 • SoRI-20041
Enzyme inhibitors
Anabolism
PAH inhibitors 3,4-Dihydroxystyrene
TH inhibitors 3-IodotyrosineAquayamycinBulbocapnineMetirosineOudenone
AAAD/DDC inhibitors BenserazideCarbidopaGenisteinMethyldopa
Catabolism
MAO inhibitors Nonselective: BenmoxinCaroxazoneEchinopsidineFurazolidoneHydralazineIndantadolIproclozideIproniazidIsocarboxazidIsoniazidLinezolidMebanazineMetfendrazineNialamideOctamoxinParaxazonePhenelzinePheniprazinePhenoxypropazinePivalylbenzhydrazineProcarbazineSafrazineTranylcypromine; MAO-A selective: AmiflamineBazinaprineBefloxatoneBefolBrofaromineCimoxatoneClorgilineEsuproneHarmala alkaloidsMethylene BlueMetralindoleMinaprineMoclobemidePirlindoleSercloremineTetrindoleToloxatoneTyrima; MAO-B selective: D-DeprenylL-Deprenyl (Selegiline) • LadostigilLazabemideMilacemidePargylineRasagilineSafinamide
COMT inhibitors EntacaponeTolcapone
DBH inhibitors DisulfiramDopastinFusaric acidNepicastatTropolone
Others
Precursors L-PhenylalanineL-TyrosineL-DOPA (Levodopa)
Cofactors Ferrous iron (Fe2+) • TetrahydrobiopterinVitamin B3 (Niacin, NicotinamideNADPH) • Vitamin B6 (Pyridoxine, Pyridoxamine, PyridoxalPyridoxal phosphate) • Vitamin B9 (Folic acidTetrahydrofolic acid) • Vitamin C (Ascorbic acid) • Zinc (Zn2+)
Others Activity enhancers: Benzofuranylpropylaminopentane (BPAP) • Phenylpropylaminopentane (PPAP); Toxins: Oxidopamine (6-Hydroxydopamine)
List of dopaminergic drugs

Categories:

 

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