generation run 2026-05-11
65 min completedmodel pipeline-v5plan not recordedrun/43a57409…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
- safety_data_unverified
Reproduce
- inputs
- 26 source keys (listed under Sources)
- plan
- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
- model
- pipeline-v5
- streams
- none — agent transcripts are persisted from 2026-09 onward
18 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed · absence | dichloropane RTI-111 dopamine reuptake inhibitor tropane | 0 | — | — |
| 2 | ClinicalTrials.gov · absence | dichloropane RTI-111 cocaine dopamine transporter | 0 | — | — |
| 3 | PubChem | methyl (1R,2S,3S,5S)-3-(3,4-dichlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate | 1 | 1 | Investigating nortropane vs N-methyl tropane discrepancy |
| 4 | Web | RTI-111 dichloropane binding affinity DAT SERT NET Ki cocaine analog pharmacology | 10 | 3 | Specific binding affinity values not found in PubMed abstracts |
| 5 | PubMed | RTI 111 phenyltropane cocaine self-administration rhesus monkey | 2 | 2 | Direct RTI-111 behavioral pharmacology data |
| 6 | NCATS Inxight Drugs | — | — | — | — |
| 7 | PubChem | dichloropane | 1 | 1 | Primary chemical identity verification |
| 8 | PubMed | 3,4-dichlorophenyl tropane cocaine analogue binding affinity | 15 | 4 | Directly relevant to 3,4-dichlorophenyl tropane pharmacology |
| 9 | PubMed | PMID 8464040 | — | 1 | — |
| 10 | PubMed/web | dichloropane saliva detection | 1 | 1 | — |
| 11 | Web/Vermont Law Cornell | Vermont regulated drugs dichloropane RTI-111 | — | — | — |
| 12 | PubMed | PMID 8164265 | — | 1 | — |
| 13 | Web | dichloropane EMCDDA EU early warning 2016 | — | — | — |
| 14 | Web | dichloropane research chemical market first appeared 2010 | — | — | — |
| 15 | MGH Martinos Center | — | — | — | — |
| 16 | BenchChem | — | — | — | — |
| 17 | Web | MAOI SNDRI interaction serotonin syndrome | — | — | — |
| 18 | PubChem | CID 9797476 | — | — | — |
47 claims by section — every cited sentence, checked against its source
safety9 · 7 ok
Compulsive redosing: Dichloropane functions as a positive reinforcer in primate self-administration models, indicating liability for compulsive use, though slower onset may partially attenuate this risk relative to cocaine.supported
Studied RTI-111 (dichloropane) reinforcing and discriminative stimulus effects in rhesus monkeys, and interaction with methamphetamine. pmid:11255920
Compulsive redosing: Dichloropane functions as a positive reinforcer in primate self-administration models, indicating liability for compulsive use, though slower onset may partially attenuate this risk relative to cocaine.partially supported
Slower-onset nonselective analog RTI-112 did not produce behavioral-stimulant effects. Onset rate more important than duration. pmid:17258302
Claim in safety — inconclusiveinconclusiveworking →
The phenyltropane class generally shows lower reinforcing strength than cocaine, attributed to slower onset of DAT occupancysupported
Rate of DAT binding inversely correlated with reinforcing efficacy. sj.npp.1300795
The phenyltropane class generally shows lower reinforcing strength than cocaine, attributed to slower onset of DAT occupancysupported
Slow-onset DAT-selective uptake inhibitors have lower abuse liability than cocaine. j.pbb.2010.05.017
The phenyltropane class generally shows lower reinforcing strength than cocaine, attributed to slower onset of DAT occupancysupported
slower uptake correlated with fewer drug infusions j.pbb.2008.03.032
However, dichloropane functions as a positive reinforcer in primate models and produces cocaine-like discriminative stimulus effects, confirming non-negligible abuse potentialsupported
Studied RTI-111 (dichloropane) reinforcing and discriminative stimulus effects in rhesus monkeys, and interaction with methamphetamine. pmid:11255920
Claim in safety — inconclusiveinconclusiveworking →
Non-DAT-selective analogs such as the structurally similar RTI-112 may have lower abuse potential than DAT-selective compounds, though this relationship is complex.supported
Slower-onset nonselective analog RTI-112 did not produce behavioral-stimulant effects. Onset rate more important than duration. pmid:17258302
history7 · 6 ok
A dedicated analytical method for dichloropane detection in oral fluids — microextraction by packed sorbent coupled with ion mobility spectrometry (MEPS-IMS) — was validated by Sorribes-Soriano and colleagues in 2019, achieving a limit of detection of 30 µg/Lsupported
MEPS-IMS method developed for dichloropane detection in oral fluids. LOD 30 microg/L. j.chroma.2019.06.054
Claim in history — inconclusiveinconclusiveworking →
Among the analogs characterized, dichloropane exhibited the highest affinity for the dopamine transporter, leading the authors to describe it as "one of the most potent cocaine congeners yet reported".supported
The synthesis and binding affinity of 3beta-(3,4-dichlorophenyl)tropane-2beta-carboxylic acid methyl ester, one of the most potent cocaine congeners yet reported, is presented. pmid:8464040
Dichloropane was studied preclinically in self-administration and discriminative stimulus paradigms in rhesus monkeys and rats, and was evaluated as a PET imaging probe for dopamine terminalssupported
Studied RTI-111 (dichloropane) reinforcing and discriminative stimulus effects in rhesus monkeys, and interaction with methamphetamine. pmid:11255920
Dichloropane was studied preclinically in self-administration and discriminative stimulus paradigms in rhesus monkeys and rats, and was evaluated as a PET imaging probe for dopamine terminalssupported
Cocaine congeners as PET imaging probes for dopamine terminals pmid:8965196
Despite its potency, dichloropane was not selected for clinical development; RTI-336 advanced as the lead candidate from the programsupported
Development of the dopamine transporter selective RTI-336 as a pharmacotherapy for cocaine abuse aapsj080124
The rhodamine-labeled analog JHC 1-64, used to visualize DAT trafficking in live neurons and to study postendocytic sorting of constitutively internalized DAT, was derived from the dichloropane core structure.supported
DAT trafficking studied using JHC 1-64 (fluorescent cocaine analog derived from dichloropane scaffold). DAT endocytosed and sorted to late endosomes/lysosomes. jbc.m110.131003
clinical-evidence6 · 5 ok
Dichloropane was evaluated within the RTI International phenyltropane program, which sought to develop a long-acting, low-abuse-potential dopamine transporter ligand for cocaine addiction pharmacotherapysupported
Review of discovery and preclinical development of selective dopamine reuptake inhibitors as pharmacotherapies for cocaine addiction; RTI series including RTI-111 compounds discussed. aapsj080124
The program's lead candidate, RTI-336, advanced further in preclinical development on the basis of superior DAT selectivity and a more favorable reinforcing-efficacy profilesupported
Development of the dopamine transporter selective RTI-336 as a pharmacotherapy for cocaine abuse aapsj080124
Self-administration and discriminative stimulus (rhesus monkeys): Ranaldi and colleagues directly studied RTI-111 for reinforcing and discriminative stimulus effects and its interaction with methamphetamine.supported
Studied RTI-111 (dichloropane) reinforcing and discriminative stimulus effects in rhesus monkeys, and interaction with methamphetamine. pmid:11255920
Claim in clinical-evidence — inconclusiveinconclusiveworking →
The rhodamine-labeled analog JHC 1-64 was developed for live-neuron DAT visualization, enabling direct observation of dopamine transporter trafficking and postendocytic sorting — applications that exploit dichloropane's high DAT affinity without requiring it to function as a therapeutic agent.supported
Novel fluorescently tagged cocaine analogs based on 2beta-carbomethoxy-3beta-(3,4-dichlorophenyl)tropane (dichloropane) used to visualize DAT trafficking in cultured live midbrain dopaminergic neurons. jneurosci.4177-08.2009
The rhodamine-labeled analog JHC 1-64 was developed for live-neuron DAT visualization, enabling direct observation of dopamine transporter trafficking and postendocytic sorting — applications that exploit dichloropane's high DAT affinity without requiring it to function as a therapeutic agent.supported
DAT trafficking studied using JHC 1-64 (fluorescent cocaine analog derived from dichloropane scaffold). DAT endocytosed and sorted to late endosomes/lysosomes. jbc.m110.131003
comparative-pharmacology6 · 5 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
This difference is attributable to the nortropane nitrogen, which enhances SERT and NET affinity without proportionally increasing DAT affinity.supported
N-Demethylation of cocaine and 3beta-(substituted phenyl)tropane analogues produced 4-19-fold enhanced SERT affinity and 2-44-fold NET affinity, with relatively small effects at DAT. pmid:8164265
The rate of DAT occupancy onset is a key determinant of stimulant reinforcing effects in the phenyltropane series — slower-onset compounds produce reduced reinforcing strength relative to cocaine.supported
Rate of drug uptake corresponded with time to peak discriminative stimulus effects; slower uptake correlated with fewer drug infusions. j.pbb.2008.03.032
RTI-112, the structurally closest published analog (3'-methyl-4'-chlorophenyl), failed to produce behavioral stimulant effects in squirrel monkeys due to its similarly slow onset and nonselective profile.supported
Slower-onset nonselective analog RTI-112 did not produce behavioral-stimulant effects. Onset rate more important than duration. pmid:17258302
The broader phenyltropane class generally shows lower reinforcing strength than cocaine, attributed to slower onset of DAT occupancysupported
Rate of DAT binding inversely correlated with reinforcing efficacy. sj.npp.1300795
The broader phenyltropane class generally shows lower reinforcing strength than cocaine, attributed to slower onset of DAT occupancysupported
slower uptake correlated with fewer drug infusions j.pbb.2008.03.032
neuroscience5 · 1 ok
Dichloropane functions as a positive reinforcer in rhesus monkey self-administration models and produces cocaine-like discriminative stimulus effects in rats, confirming engagement of the mesolimbic reward circuitsupported
Studied RTI-111 (dichloropane) reinforcing and discriminative stimulus effects in rhesus monkeys, and interaction with methamphetamine. pmid:11255920
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
receptor-pharmacology4 · 2 ok
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Carroll and colleagues confirmed that 3β-(3',4'-disubstituted phenyl)tropane-2β-carboxylic acid methyl esters generally produce subnanomolar IC₅₀ values at both DAT and SERT for most compounds with 3',4'-disubstitution patternssupported
Subnanomolar IC50 values at DAT and SERT for most compounds; 3,4-dichloro analog (dichloropane parent) in same structural series. pmid:15828814
Jin and colleagues developed phenyltropane analogs with deliberately tuned DAT/SERT selectivity, demonstrating that the transporter selectivity of this scaffold class can be systematically modulated through aromatic ring substitution and nitrogen modificationsupported
Series of 3beta-(substituted phenyl)tropane-2beta-carboxylic acid methyl esters synthesized; compounds with high DAT and SERT affinity and low NET affinity identified. jm801162z
summary4 · 3 ok
Claim in summary — inconclusiveinconclusiveworking →
First synthesized in 1993 by Meltzer and colleagues at Massachusetts General Hospital as part of a systematic evaluation of cocaine congeners, dichloropane was described as "one of the most potent cocaine congeners yet reported"supported
The synthesis and binding affinity of 3beta-(3,4-dichlorophenyl)tropane-2beta-carboxylic acid methyl ester, one of the most potent cocaine congeners yet reported, is presented. pmid:8464040
It was subsequently studied within the RTI International phenyltropane program as a potential cocaine pharmacotherapy but was not selected for clinical development; RTI-336 advanced as the lead candidatesupported
Review of discovery and preclinical development of selective dopamine reuptake inhibitors as pharmacotherapies for cocaine addiction; RTI series including RTI-111 compounds discussed. aapsj080124
The nortropane (secondary amine) nitrogen enhances SERT affinity 4–19-fold and NET affinity 2–44-fold relative to N-methyl tropane analogssupported
N-Demethylation of cocaine and 3beta-(substituted phenyl)tropane analogues produced 4-19-fold enhanced SERT affinity and 2-44-fold NET affinity, with relatively small effects at DAT. pmid:8164265
pharmacology3 · 1 ok
Claim in pharmacology — inconclusiveinconclusiveworking →
N-demethylation of phenyltropane cocaine analogs produces 4–19-fold enhancement of SERT affinity and 2–44-fold enhancement of NET affinity with minimal change at DAT, relative to the corresponding N-methyl tropane parent compoundssupported
N-Demethylation of cocaine and 3beta-(substituted phenyl)tropane analogues produced 4-19-fold enhanced SERT affinity and 2-44-fold NET affinity, with relatively small effects at DAT. pmid:8164265
Claim in pharmacology — inconclusiveinconclusiveworking →
chemistry2 · 0 ok
pharmacokinetic-detail1 · 0 ok
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →