DPT

DPT is a mixed serotonergic agent whose pharmacological activity arises from the convergence of direct receptor agonism and transporter-mediated monoamine release — a dual mechanism that places it between the purely receptor-mediated action of DMT and the predominantly transporter-mediated action of MDMA.supported

DPT characterized as mixed 5-HT2A agonist/monoamine reuptake inhibitor. jpet.109.156174

The primary psychedelic mechanism is 5-HT₂A receptor full agonism (Ki = 152 nM, EC50 = 445 nM for G-protein coupling via TRUPATH Gα/βγ biosensors)supported

5-HT2A Ki=152 nM (full agonist, EC50=445 nM). acsptsci.3c00137

The selective 5-HT₂A antagonist MDL100907 produces functionally insurmountable antagonism of DPT's head-twitch response (HTR) in mice and drug discrimination effects in rats and primatessupported

M100907 (5-HT2A antagonist) effects functionally insurmountable... 5-HT2A receptor is important site of action. pmid:17905422

The selective 5-HT₂A antagonist MDL100907 produces functionally insurmountable antagonism of DPT's head-twitch response (HTR) in mice and drug discrimination effects in rats and primatessupported

DPT 3.2 mg/kg produced >95% responding on DOM lever (blocked by MDL100907). pmid:17551320

The selective 5-HT₂A antagonist MDL100907 produces functionally insurmountable antagonism of DPT's head-twitch response (HTR) in mice and drug discrimination effects in rats and primatespartially supported

5-HT2A antagonists (MDL100907, ketanserin, ritanserin) produced parallel rightward shifts. pA2 for MDL100907 vs DPT = 8.50. jpet.108.145458

Schild analysis in rhesus monkeys yields pA₂ = 8.50 for MDL100907 against DPT, quantitatively confirming 5-HT₂A as the primary mediator of the hallucinogenic discriminative stimulus.supported

pA2 for MDL100907 vs DPT = 8.50. Quantitative evidence for 5-HT2A as primary mediator of DPT discriminative effects in primates. jpet.108.145458

DPT acts as a 5-HT₁A partial agonist (Ki = 1640 nM, EC50 = 2400 nM, 52% intrinsic activity), with IC50 = 0.1 µmol/L at cloned human 5-HT₁A in competitive interaction with [³H]8-OH-DPATpartially supported

5-HT1A Ki=1640 nM (partial 52%). acsptsci.3c00137

DPT acts as a 5-HT₁A partial agonist (Ki = 1640 nM, EC50 = 2400 nM, 52% intrinsic activity), with IC50 = 0.1 µmol/L at cloned human 5-HT₁A in competitive interaction with [³H]8-OH-DPATsupported

IC50 0.1 μmol/L at human 5-HT1A. Competitive interaction with 8-OH-DPAT... Moderate affinity partial agonist at human 5-HT1A receptor. pmid:15886504

This 5-HT₁A activity is ordinarily masked by dominant 5-HT₂A agonism at typical doses; when 5-HT₂A is pharmacologically blocked, 5-HT₁A effects emerge as flat body posture and lower-lip retraction in rats, both attenuated by the 5-HT₁A antagonist WAY-100635partially supported

DPT produced flat body posture (5-HT1A); masked 5-HT1A agonism unmasked by MDL100907 pretreatment. pmid:17551320

WAY-100635 produces a surmountable rightward shift of DPT's HTR dose–effect curve in micesupported

WAY-100635 (5-HT1A) produced surmountable rightward shift. pmid:17905422

Binding to 5-HT₁A is thermodynamically entropy-driven.supported

Thermodynamic parameters for DPT (partial agonist) at human 5-HT1A; binding events are highly entropy-driven. 000312684

Beyond receptor agonism, DPT functions as a SERT substrate (KI = 0.594 ± 0.12 µM at human platelet SERT), entering serotonergic neurons via the transporter and displacing intracellular serotonin into the synapsesupported

DPT KI for SERT inhibition = 0.594 ± 0.12 μM... High binding-to-uptake ratios indicate substrate (not blocker) behavior at both SERT and VMAT2. s00702-009-0308-8

DPT also inhibits monoamine reuptake at DAT and NET in rat brain synaptosomes with minimal direct release effectssupported

DPT inhibits monoamine re-uptake (dopamine, 5-HT, norepinephrine) but has few effects on monoamine release in rat brain synaptosomes. pmid:17223101

DPT is a VMAT2 substrate (KI = 19 ± 2.3 µM), enabling intracellular vesicular accumulationsupported

KI for VMAT2 = 19 ± 2.3 μM. High binding-to-uptake ratios indicate substrate (not blocker) behavior at both SERT and VMAT2. s00702-009-0308-8

Claim in pharmacology — inconclusiveinconclusiveworking →

Cozzi and colleagues proposed that this accumulation could activate sigma-1 receptors intracellularly, but the selective sigma-1 antagonist NE-100 did not block DPT's anticonvulsant effects in Fmr1 knockout mice — the anticonvulsant mechanism remains unidentified.supported

Anticonvulsant mechanism appears independent of 5-HT2A/2C, 5-HT1B, 5-HT1A, and sigma1 receptors. acsptsci.3c00137

The full mechanistic hierarchy is: (1) 5-HT₂A full agonism, (2) 5-HT₁A partial agonism, (3) SERT-mediated serotonin release, (4) VMAT2 substrate accumulation, (5) an unidentified anticonvulsant mechanism independent of serotonin and sigma-1 receptors.supported

5-HT2A Ki=152 nM (full agonist)... 5-HT1A Ki=1640 nM (partial 52%)... Anticonvulsant mechanism appears independent of 5-HT2A/2C, 5-HT1B, 5-HT1A, and sigma1 receptors. acsptsci.3c00137

Claim in pharmacology — inconclusiveinconclusiveworking →

Claim in pharmacology — inconclusiveinconclusiveworking →

The single published fatal case involves a 20-year-old male with prior hallucinogen experience who insufflated an unknown quantity of DPTsupported

20-year-old man with prior hallucinogen-use experience, who sniffed an unknown amount of dipropyltryptamine. j.jpba.2023.115959

DPT exhibits dose-dependent effects on seizure thresholdsupported

DPT completely prevents audiogenic seizures... at 10 mg/kg... Proconvulsant at high doses (20+ mg/kg). acsptsci.3c00137

The fatal human case involved seizure at approximately 2 hours post-insufflation, consistent with high-dose proconvulsant risk.supported

Two hours post consumption he developed abdominal pain, leading to collapse, seizure, and vomiting. j.jpba.2023.115959

Claim in safety — inconclusiveinconclusiveworking →

Claim in safety — inconclusiveinconclusiveworking →

Daily DPT administration does not produce tolerance to the head-twitch response in mice, contrasting with phenethylamine hallucinogens (DOI, 2C-T-7) which rapidly develop tolerancesupported

Tolerance develops to daily DOI/2C-T-7 HTR but not to DPT or DIPT. jpet.114.219337

Insurmountable cross-tolerance from DOI to DPT occurs — DOI-tolerant mice show reduced DPT response — but the reverse direction was not testedsupported

DOI-tolerant mice showed insurmountable cross-tolerance to DPT. jpet.114.219337

Claim in safety — inconclusiveinconclusiveworking →

Drug discrimination data confirm DPT serves as its own discriminative stimulus, indicating reinforcing stimulus properties, but no self-administration paradigms have tested reinforcement directlysupported

DPT tested in head-twitch assay in mice and drug discrimination in rats (LSD, psilocybin, MDMA cues). pmid:17905422

Other 5-HT₂A agonists produce additive discriminative stimulus effects with DPT in animal models. 5-HT₁A receptor agonists show species-specific modulation: they attenuate the DOM discriminative stimulus in monkeys but not ratssupported

DPT and 2C-T-7 enhanced DOM discriminative stimulus additively; 5-HT1A agonists attenuated DOM effects in monkeys but not rats. jpet.109.163451

Other 5-HT₂A agonists produce additive discriminative stimulus effects with DPT in animal models. 5-HT₁A receptor agonists show species-specific modulation: they attenuate the DOM discriminative stimulus in monkeys but not ratssupported

DPT and 2C-T-7 enhanced DOM discriminative stimulus additively; 5-HT1A agonists attenuated DOM effects in monkeys but not rats. jpet.109.163451

Claim in safety — not_supportednot supportedworking →

DPT is proconvulsant at high doses in animal models, and the single fatal human case involved seizure.supported

Proconvulsant at high doses (20+ mg/kg). acsptsci.3c00137

DPT is proconvulsant at high doses in animal models, and the single fatal human case involved seizure.supported

Two hours post consumption he developed abdominal pain, leading to collapse, seizure, and vomiting. j.jpba.2023.115959

DPT does not produce tolerance to its own effects in mice, contrasting sharply with phenethylamine psychedelics, though cross-tolerance from the phenethylamine class extends to DPTsupported

Tolerance develops to daily DOI/2C-T-7 HTR but not to DPT or DIPT. DOI-tolerant mice showed insurmountable cross-tolerance to DPT. jpet.114.219337

First synthesized in the early 1950s during systematic N,N-dialkyl tryptamine exploration, DPT was characterized as psychoactive in humans during the 1960spartially supported

DPT is a synthetic indolealkylamine first characterized in the 1960s. pmid:15886504

Claim in summary — inconclusiveinconclusiveworking →

Claim in summary — inconclusiveinconclusiveworking →

DPT acts as a full agonist at 5-HT₂A receptors (Ki = 152 nM, EC50 = 445 nM) and a partial agonist at 5-HT₁A (Ki = 1640 nM, 52% intrinsic activity)supported

5-HT2A Ki=152 nM (full agonist, EC50=445 nM), 5-HT1A Ki=1640 nM (partial 52%). acsptsci.3c00137

Functionally insurmountable antagonism by the selective 5-HT₂A antagonist MDL100907 confirms 5-HT₂A as the primary hallucinogenic target across mice, rats, and primatessupported

M100907 (5-HT2A antagonist) effects functionally insurmountable... 5-HT2A receptor is important site of action. pmid:17905422

Functionally insurmountable antagonism by the selective 5-HT₂A antagonist MDL100907 confirms 5-HT₂A as the primary hallucinogenic target across mice, rats, and primatespartially supported

5-HT2A antagonists (MDL100907, ketanserin, ritanserin) produced parallel rightward shifts. pA2 for MDL100907 vs DPT = 8.50. jpet.108.145458

Uniquely among classical psychedelics, DPT also functions as a SERT substrate (KI = 0.594 µM), producing transporter-mediated serotonin release alongside direct receptor agonism.supported

DPT KI for SERT inhibition = 0.594 ± 0.12 μM... High binding-to-uptake ratios indicate substrate (not blocker) behavior at both SERT and VMAT2. s00702-009-0308-8

Claim in summary — inconclusiveinconclusiveworking →

Claim in summary — inconclusiveinconclusiveworking →

The single published fatal case involved aspiration secondary to seizure, not confirmed pharmacological overdosesupported

Two hours post consumption he developed abdominal pain, leading to collapse, seizure, and vomiting. j.jpba.2023.115959

Animal data reveal a complex dose-dependent seizure profile: anticonvulsant at 10 mg/kg, proconvulsant at ≥20 mg/kgsupported

DPT completely prevents audiogenic seizures (AGS) in Fmr1 KO mice at 10 mg/kg... Proconvulsant at high doses (20+ mg/kg). acsptsci.3c00137

Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

The 5-HT₂A target is confirmed as the primary mediator of hallucinogenic activity through multiple convergent lines of evidence: the selective 5-HT₂A antagonist MDL100907 produces functionally insurmountable antagonism of DPT's head-twitch response in mice, blocks DPT's drug discrimination effects in rats and primates, and yields a Schild analysis pA₂ of 8.50 in rhesus monkeys — indicating high-affinity competitive antagonism at the receptor mediating the discriminative stimulus.supported

M100907 (5-HT2A antagonist) effects functionally insurmountable... 5-HT2A receptor is important site of action. pmid:17905422

The 5-HT₂A target is confirmed as the primary mediator of hallucinogenic activity through multiple convergent lines of evidence: the selective 5-HT₂A antagonist MDL100907 produces functionally insurmountable antagonism of DPT's head-twitch response in mice, blocks DPT's drug discrimination effects in rats and primates, and yields a Schild analysis pA₂ of 8.50 in rhesus monkeys — indicating high-affinity competitive antagonism at the receptor mediating the discriminative stimulus.supported

DPT 3.2 mg/kg produced >95% responding on DOM lever (blocked by MDL100907). pmid:17551320

The 5-HT₂A target is confirmed as the primary mediator of hallucinogenic activity through multiple convergent lines of evidence: the selective 5-HT₂A antagonist MDL100907 produces functionally insurmountable antagonism of DPT's head-twitch response in mice, blocks DPT's drug discrimination effects in rats and primates, and yields a Schild analysis pA₂ of 8.50 in rhesus monkeys — indicating high-affinity competitive antagonism at the receptor mediating the discriminative stimulus.supported

pA2 for MDL100907 vs DPT = 8.50. Quantitative evidence for 5-HT2A as primary mediator of DPT discriminative effects in primates. jpet.108.145458

Independent confirmation of 5-HT₁A binding comes from Thiagaraj and colleagues, who reported IC50 = 0.1 µmol/L at cloned human 5-HT₁A via competitive interaction with [³H]8-OH-DPATsupported

IC50 0.1 μmol/L at human 5-HT1A. Competitive interaction with 8-OH-DPAT. pmid:15886504

WAY-100635 (5-HT₁A antagonist) produces a surmountable rightward shift of the HTR dose–effect curve in mice, while pharmacological blockade of 5-HT₂A in rats unmasks 5-HT₁A agonist activity — flat body posture and lower-lip retraction, both attenuated by WAY-100635.supported

WAY-100635 (5-HT1A) produced surmountable rightward shift. pmid:17905422

WAY-100635 (5-HT₁A antagonist) produces a surmountable rightward shift of the HTR dose–effect curve in mice, while pharmacological blockade of 5-HT₂A in rats unmasks 5-HT₁A agonist activity — flat body posture and lower-lip retraction, both attenuated by WAY-100635.partially supported

DPT produced flat body posture (5-HT1A); masked 5-HT1A agonism unmasked by MDL100907 pretreatment. pmid:17551320

Values from Cozzi and colleaguessupported

DPT KI for SERT inhibition = 0.594 ± 0.12 μM... KI for VMAT2 = 19 ± 2.3 μM. s00702-009-0308-8

DPT inhibits monoamine reuptake at DAT and NET in rat brain synaptosomes with minimal direct monoamine release, supporting substrate rather than amphetamine-like releasing behavior.supported

DPT inhibits monoamine re-uptake (dopamine, 5-HT, norepinephrine) but has few effects on monoamine release in rat brain synaptosomes. pmid:17223101

Ray profiled DPT across 51 receptor and transporter sites using NIMH Psychoactive Drug Screening Program datasupported

Receptor affinity pharmacology of 25 psychedelic drugs at 51 receptors, transporters, and ion channels (NIMH-PDSP). journal.pone.0009019

DPT's 5-HT₂A Ki of 152 nM places it at lower affinity than DMT (Ki typically 50–100 nM at 5-HT₂A), consistent with DPT's requirement for higher absolute doses (100–250 mg oral vs. negligible oral activity for DMT without MAO inhibition)supported

5-HT2A Ki=152 nM (full agonist, EC50=445 nM). acsptsci.3c00137

DPT produces >95% DOM-lever responding at 3.2 mg/kg in DOM-trained ratssupported

DPT 3.2 mg/kg produced >95% responding on DOM lever (blocked by MDL100907). pmid:17551320

While DMT and psilocybin operate primarily through direct 5-HT₂A receptor agonism, and MDMA acts predominantly through transporter-mediated monoamine release, DPT combines both mechanisms — full 5-HT₂A agonism and SERT substrate behavior.supported

DPT characterized as mixed 5-HT2A agonist/monoamine reuptake inhibitor. jpet.109.156174

In GTPγS functional assays, DPT ranks among the lower-potency tryptamines: 5-MeO-DMT > 5-MeO-DALT > 5-MeO-AMT ≥ 5-MeO-MIPT > 5-MeO-DIPT > DPT ≥ AMT.supported

Rank order: 5-MeO-DMT > 5-MeO-DALT > 5-MeO-AMT >= 5-MeO-MIPT > 5-MeO-DIPT > DPT >= AMT. pmid:18057721

DPT fully substitutes for LSD and psilocybin discriminative stimuli in ratssupported

DPT tested in head-twitch assay in mice and drug discrimination in rats (LSD, psilocybin, MDMA cues). pmid:17905422

At high doses, DPT shows some PCP-like discriminative stimulus effects in rat drug discriminationsupported

DPT produced moderate PCP-lever selection and behavioral disruption at highest dose in PCP-trained rats. j.neuropharm.2017.08.028

Daily administration does not produce tolerance to the head-twitch response in mice, contrasting sharply with phenethylamine hallucinogens (DOI, 2C-T-7) which rapidly develop tolerancesupported

Tolerance develops to daily DOI/2C-T-7 HTR but not to DPT or DIPT. jpet.114.219337

The dose-dependent seizure threshold effects — anticonvulsant at 10 mg/kg, proconvulsant at ≥20 mg/kg in mice — indicate DPT modulates cortical excitability through a mechanism independent of both serotonin receptors and sigma-1 receptorssupported

DPT completely prevents audiogenic seizures (AGS) in Fmr1 KO mice at 10 mg/kg... Proconvulsant at high doses (20+ mg/kg)... Anticonvulsant mechanism appears independent of 5-HT2A/2C, 5-HT1B, 5-HT1A, and sigma1 receptors. acsptsci.3c00137

DPT's concurrent SERT substrate behavior — releasing serotonin into the synapse — adds a transporter-mediated serotonergic surge that pure receptor agonists like DMT do not producesupported

High binding-to-uptake ratios indicate substrate (not blocker) behavior at both SERT and VMAT2. s00702-009-0308-8

Claim in neuroscience — inconclusiveinconclusiveworking →

What neural mechanism underlies DPT's dose-dependent seizure threshold effects, given that neither serotonin receptor antagonism nor sigma-1 antagonism blocks the anticonvulsant effect?supported

Anticonvulsant mechanism appears independent of 5-HT2A/2C, 5-HT1B, 5-HT1A, and sigma1 receptors. acsptsci.3c00137

What is DPT's receptor occupancy profile at therapeutic doses across the 51 targets identified by Ray?supported

Receptor affinity pharmacology of 25 psychedelic drugs at 51 receptors, transporters, and ion channels (NIMH-PDSP). journal.pone.0009019

Human psychedelic properties were established during the 1960s — Thiagaraj and colleagues describe DPT as "a synthetic indolealkylamine first characterized in the 1960s"supported

DPT is a synthetic indolealkylamine first characterized in the 1960s. pmid:15886504

The first published clinical study examined low-dose DPT as an adjunct to psychotherapysupported

Clinical study on low-dose DPT use as psychotherapy adjunct. pmid:4575167

Claim in history — inconclusiveinconclusiveworking →

Claim in history — inconclusiveinconclusiveworking →

Soskin, Grof, and Richards published the first clinical study of DPT as a psychotherapy adjunct, examining low-dose protocolssupported

Clinical study on low-dose DPT use as psychotherapy adjunct. pmid:4575167

Grof, Soskin, Richards, and Kurland conducted a controlled study in 103 male adult alcoholic patientssupported

No abstract available. Controlled study of DPT-assisted psychotherapy in alcoholics. pmid:4150711

This trial is included in two systematic reviews of serotonergic hallucinogens for terminal illness: Reiche and colleagues (2018) and Schimmers and colleagues (2022).supported

Systematic review of psychedelics for existential distress in life-threatening diseases. 11 eligible trials N=445. One DPT trial (N=30). j.pnpbp.2017.09.012

DPT's subjective character is shaped by its dual pharmacological mechanism — direct 5-HT₂A agonism layered with transporter-mediated serotonin releasesupported

High binding-to-uptake ratios indicate substrate (not blocker) behavior at both SERT and VMAT2. s00702-009-0308-8

Claim in effects-overview — inconclusiveinconclusiveworking →

DPT sits between DMT and MDMA in experiential charactersupported

DPT substituted for both S(+)-MDMA and R(-)-MDMA cues; DPT characterized as mixed 5-HT2A agonist/monoamine reuptake inhibitor. jpet.109.156174

Insufflated onset from fatal case report.supported

sniffed an unknown amount of dipropyltryptamine... Ten to fifteen minutes later he experienced visual hallucinations. j.jpba.2023.115959

Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →