4-AcO-MiPT

Malcolm (2022) identified psychedelic 5-HT₂A agonists combined with serotonergic drugs as a clinically important drug-drug interaction category.supported

Evaluates drug-drug interaction risks and serotonin toxicity between psychedelic serotonergic substances and SSRIs. s00213-021-05876-x

A 2022 systematic review of NPS adverse events from 2017 to 2020 did not identify any confirmed cases involving 4-AcO-MiPT or 4-OH-mipt.supported

Review of 1,319 NPS adverse events cases 2017-2020. 4-HO-MiPT not among the 60+ NPS with confirmed adverse events. bkac023

Claim in safety — inconclusiveinconclusiveworking →

Helander et al. (2014) documented clinical presentations of tryptamine NPS intoxications in Swedish emergency departments via the STRIDA surveillance project, observing that polydrug use complicates attribution of effects to individual compoundssupported

STRIDA project monitors NPS including hallucinogenic tryptamines in emergency settings. Documents toxicity and clinical presentations of NPS intoxications. j.forsciint.2014.02.022

Rapid tolerance to the psychedelic effects of 4-AcO-MiPT is expected, consistent with the class-wide mechanism of 5-HT₂A downregulation following agonist exposurepartially supported

Beta-arrestin-biased ligands block psychedelic effects and induce receptor downregulation and tachyphylaxis. s41467-023-44016-1

Wallach et al. (2023) demonstrated that beta-arrestin-biased ligands — and to a lesser extent Gq-biased partial agonists — induce 5-HT₂A receptor internalization, providing the molecular basis for rapid tachyphylaxispartially supported

5-HT2A-Gq (not beta-arrestin2) efficacy predicts psychedelic potential via head-twitch response magnitude in mice. Beta-arrestin-biased ligands block psychedelic effects and induce receptor downregulation and tachyphylaxis. s41467-023-44016-1

Cross-tolerance with other serotonergic psychedelics — including lsd, psilocybin, and dmt — is expected via the shared 5-HT₂A downregulation mechanism.supported

5-HT2A-Gq (not beta-arrestin2) efficacy predicts psychedelic potential via head-twitch response magnitude in mice. Beta-arrestin-biased ligands block psychedelic effects and induce receptor downregulation and tachyphylaxis. s41467-023-44016-1

Gatch et al. (2021) noted that substituted tryptamines show abuse-liability "similar to dom" in drug discrimination paradigms, but this reflects stimulus generalization rather than compulsive self-administration or dose escalation.supported

All tested compounds suggest abuse liability similar to DOM. acsptsci.0c00173

Claim in safety — inconclusiveinconclusiveworking →

Tramadol: Classified as a dangerous combination. tramadol inhibits serotonin reuptake at SERT while simultaneously acting as a MOR agonistsupported

Reviews tramadol as SERT inhibitor. Tramadol inhibits human SERT in HEK293 cells. Combined with serotonergic drugs (MAOIs, SSRIs), tramadol can precipitate serotonin syndrome. s00204-018-2244-6

Combined with 5-HT₂A agonism from 4-OH-MiPT, the dual serotonergic challenge creates clinically significant serotonin syndrome risksupported

Evaluates drug-drug interaction risks and serotonin toxicity between psychedelic serotonergic substances and SSRIs. s00213-021-05876-x

Tramadol-induced serotonin syndrome is a documented adverse outcome in published case seriessupported

Systematic review of tramadol-induced psychological effects including manic episodes, serotonin syndrome, psychosis, and cognitive impairment. 00912174251322356

Claim in safety — inconclusiveinconclusiveworking →

By structural analogy to psilocin, 4-OH-MiPT is presumed to undergo metabolism via cytochrome P450 2D6 and CYP3A4supported

Primary metabolism by CYP2D6 and CYP3A4; secondary MAO-A. pharmaceutics17040411

Claim in safety — inconclusiveinconclusiveworking →

Concurrent tramadol use: Serotonin syndrome risk via SERT inhibition combined with 5-HT₂A agonism. Absolute contraindicationsupported

Evaluates drug-drug interaction risks and serotonin toxicity between psychedelic serotonergic substances and SSRIs. s00213-021-05876-x

A 2022 systematic review of NPS adverse events from 2017 to 2020 did not identify any confirmed cases involving 4-AcO-MiPT or 4-OH-mipt.supported

Review of 1,319 NPS adverse events cases 2017-2020. 4-HO-MiPT not among the 60+ NPS with confirmed adverse events. bkac023

Tittarelli et al. (2015) reviewed tryptamine NPS toxicity broadly, noting that acute effects can include sympathomimetic responses (tachycardia, hypertension, hyperthermia), seizures, and serotonin-syndrome — particularly when combined with serotonergic agents or MAOIssupported

Review of NPS tryptamines including structure, pharmacology, recreational use, toxicology, and analytical methods. 1570159x13666141210222409

Helander et al. (2014) documented clinical presentations of tryptamine NPS intoxications in Swedish emergency departments via the STRIDA surveillance project, observing that polydrug use complicates attribution of effects to individual compoundssupported

STRIDA project monitors NPS including hallucinogenic tryptamines in emergency settings. Documents toxicity and clinical presentations of NPS intoxications. j.forsciint.2014.02.022

Rapid tolerance to the psychedelic effects of 4-AcO-MiPT is expected, consistent with the class-wide mechanism of 5-HT₂A downregulation following agonist exposuresupported

Beta-arrestin-biased ligands block psychedelic effects and induce receptor downregulation and tachyphylaxis. s41467-023-44016-1

Wallach et al. (2023) demonstrated that beta-arrestin-biased ligands — and to a lesser extent Gq-biased partial agonists — induce 5-HT₂A receptor internalization, providing the molecular basis for rapid tachyphylaxissupported

Beta-arrestin-biased ligands block psychedelic effects and induce receptor downregulation and tachyphylaxis. s41467-023-44016-1

Cross-tolerance with other serotonergic psychedelics — including lsd, psilocybin, and dmt — is expected via the shared 5-HT₂A downregulation mechanism.supported

Beta-arrestin-biased ligands block psychedelic effects and induce receptor downregulation and tachyphylaxis. s41467-023-44016-1

Gatch et al. (2021) noted that substituted tryptamines show abuse-liability 'similar to dom' in drug discrimination paradigms, but this reflects stimulus generalization rather than compulsive self-administration or dose escalation.supported

All tested compounds suggest abuse liability similar to DOM. acsptsci.0c00173

Claim in safety — inconclusiveinconclusiveworking →

Tramadol: Classified as a dangerous combination. tramadol inhibits serotonin reuptake at SERT while simultaneously acting as a MOR agonistsupported

Tramadol inhibits human SERT in HEK293 cells. Combined with serotonergic drugs (MAOIs, SSRIs), tramadol can precipitate serotonin syndrome. s00204-018-2244-6

Combined with 5-HT₂A agonism from 4-OH-MiPT, the dual serotonergic challenge creates clinically significant serotonin syndrome risksupported

Evaluates drug-drug interaction risks and serotonin toxicity between psychedelic serotonergic substances and SSRIs. s00213-021-05876-x

Tramadol-induced serotonin syndrome is a documented adverse outcome in published case seriessupported

Systematic review of tramadol-induced psychological effects including manic episodes, serotonin syndrome, psychosis, and cognitive impairment. 00912174251322356

Combined with a 5-HT₂A agonist, severe potentiation of both psychedelic effects and serotonin toxicity is expectedsupported

Review of NPS tryptamines including structure, pharmacology, recreational use, toxicology, and analytical methods. 1570159x13666141210222409

Malcolm (2022) identified psychedelic 5-HT₂A agonists combined with serotonergic drugs as a clinically important drug-drug interaction category.supported

Evaluates drug-drug interaction risks and serotonin toxicity between psychedelic serotonergic substances and SSRIs. Important for MDMA-SSRI and MDMA-MAOI interaction assessment. s00213-021-05876-x

By structural analogy to psilocin, 4-OH-MiPT is presumed to undergo metabolism via cytochrome P450 2D6 and CYP3A4supported

Primary metabolism by CYP2D6 and CYP3A4; secondary MAO-A. pharmaceutics17040411

Concurrent MAOI use: Severe serotonin syndrome risk via dual serotonergic mechanism. Absolute contraindicationsupported

Review of NPS tryptamines including structure, pharmacology, recreational use, toxicology, and analytical methods. 1570159x13666141210222409

Concurrent tramadol use: Serotonin syndrome risk via SERT inhibition combined with 5-HT₂A agonism. Absolute contraindicationsupported

Evaluates drug-drug interaction risks and serotonin toxicity between psychedelic serotonergic substances and SSRIs. s00213-021-05876-x

Claim in pharmacology — inconclusiveinconclusiveworking →

This prodrug relationship is supported by the approximately 7-fold difference in 5-ht2a binding affinity between the parent ester (Ki = 800 ± 100 nM) and the free hydroxyl metabolite (Ki = 113 ± 31 nM), and is further corroborated by drug discrimination studies demonstrating that 4-hydroxy tryptamines are consistently more potent than their 4-acetoxy counterparts in dom-generalization paradigms.supported

4-hydroxy compounds more potent than 4-acetoxy. All tested compounds suggest abuse liability similar to DOM. acsptsci.0c00173

Claim in pharmacology — inconclusiveinconclusiveworking →

Gq-pathway activation at 5-HT₂A — rather than beta-arrestin2 recruitment — has been identified as the signaling mechanism predicting psychedelic potential, demonstrated by correlation with head-twitch response in micesupported

5-HT2A-Gq (not beta-arrestin2) efficacy predicts psychedelic potential via head-twitch response magnitude in mice. s41467-023-44016-1

Claim in pharmacology — inconclusiveinconclusiveworking →

Downstream effectors are expected to include nmda-receptor/ampa-receptor modulation and mTOR-bdnf neuroplasticity cascades, consistent with the mechanistic framework described for serotonergic psychedelics broadly.supported

Reviews neurobiological therapeutic mechanisms via 5-HT2A/5-HT1A and NMDA/AMPA; neuroplasticity via mTOR, BDNF. pharmrev.120.000056

Claim in pharmacology — inconclusiveinconclusiveworking →

Metabolic studies of the closely related 4-aco-dipt (N,N-diisopropyl analog) in human hepatocytes identified 4-OH-dipt as the primary metabolite via ester hydrolysis, with additional phase II conjugation (glucuronidation, sulfation) and minor N-oxidation and N-dealkylation pathways yielding six total metabolitessupported

4-AcO-DiPT metabolism in human hepatocytes. Primary metabolite via ester hydrolysis is 4-OH-DiPT. Phase II: glucuronidation and sulfation. N-oxidation and N-dealkylation also occur. 6 metabolites identified. metabo12080705

This prodrug conversion parallels the well-characterized dephosphorylation of psilocybin to psilocin.supported

Systematic review of 14 psilocybin PK studies (8 lab, 6 clinical; 112 healthy humans). Psilocin Tmax 1.8–4h. pharmaceutics17040411

A systematic review of psilocybin pharmacokinetics in 112 human subjects reported psilocin (4-OH-dmt) parameters: T_max 1.8–4 hours, oral bioavailability 52.7 ± 20%, volume of distribution 277–1,016 L, half-life 1.5–4 hours, with primary metabolism via cyp2d6 and cyp3a4 and secondary metabolism via mao-asupported

Systematic review of 14 psilocybin PK studies (8 lab, 6 clinical; 112 healthy humans). Psilocin Tmax 1.8–4h; bioavailability 52.7±20%. Vd 277±92 to 1016 L. Primary metabolism by CYP2D6 and CYP3A4; secondary MAO-A. Elimination half-life 1.5–4h. pharmaceutics17040411

Claim in pharmacology — inconclusiveinconclusiveworking →

This prodrug relationship is supported by the approximately 7-fold difference in 5-ht2a binding affinity between the parent ester (Ki = 800 ± 100 nM) and the free hydroxyl metabolite (Ki = 113 ± 31 nM), and is further corroborated by drug discrimination studies demonstrating that 4-hydroxy tryptamines are consistently more potent than their 4-acetoxy counterparts in dom-generalization paradigms.supported

4-hydroxy compounds more potent than 4-acetoxy. All tested compounds suggest abuse liability similar to DOM. acsptsci.0c00173

Claim in pharmacology — inconclusiveinconclusiveworking →

Gq-pathway activation at 5-HT₂A — rather than beta-arrestin2 recruitment — has been identified as the signaling mechanism predicting psychedelic potential, demonstrated by correlation with head-twitch response in micesupported

5-HT2A-Gq (not beta-arrestin2) efficacy predicts psychedelic potential via head-twitch response magnitude in mice. s41467-023-44016-1

Claim in pharmacology — inconclusiveinconclusiveworking →

Downstream effectors are expected to include nmda-receptor/ampa-receptor modulation and mTOR-bdnf neuroplasticity cascades, consistent with the mechanistic framework described for serotonergic psychedelics broadly.supported

Reviews neurobiological therapeutic mechanisms via 5-HT2A/5-HT1A and NMDA/AMPA; neuroplasticity via mTOR, BDNF; immunomodulation; neurotransmitter modulation. pharmrev.120.000056

Claim in pharmacology — inconclusiveinconclusiveworking →

Metabolic studies of the closely related 4-aco-dipt (N,N-diisopropyl analog) in human hepatocytes identified 4-OH-dipt as the primary metabolite via ester hydrolysis, with additional phase II conjugation (glucuronidation, sulfation) and minor N-oxidation and N-dealkylation pathways yielding six total metabolitessupported

4-AcO-DiPT metabolism in human hepatocytes. Primary metabolite via ester hydrolysis is 4-OH-DiPT. Phase II: glucuronidation and sulfation. N-oxidation and N-dealkylation also occur. 6 metabolites identified. metabo12080705

This prodrug conversion parallels the well-characterized dephosphorylation of psilocybin to psilocin.supported

Systematic review of 14 psilocybin PK studies (8 lab, 6 clinical; 112 healthy humans). Psilocin Tmax 1.8–4h... pharmaceutics17040411

A systematic review of psilocybin pharmacokinetics in 112 human subjects reported psilocin (4-OH-dmt) parameters: T_max 1.8–4 hours, oral bioavailability 52.7 ± 20%, volume of distribution 277–1,016 L, half-life 1.5–4 hours, with primary metabolism via cyp2d6 and cyp3a4 and secondary metabolism via mao-asupported

Systematic review of 14 psilocybin PK studies (8 lab, 6 clinical; 112 healthy humans). Psilocin Tmax 1.8–4h; bioavailability 52.7±20%. Vd 277±92 to 1016 L. Primary metabolism by CYP2D6 and CYP3A4; secondary MAO-A. Elimination half-life 1.5–4h. pharmaceutics17040411

Chadeayne and colleagues published the crystal structure of 4-HO-MiPT fumarate monohydrate in 2019, followed by a second crystalline form — the bis(miprocinium) fumarate salt — in 2020supported

Solid-state crystal structures of MiPT fumarate and 4-HO-MiPT fumarate monohydrate. Both cations feature side-chain disorder. N-H...O and O-H...O hydrogen bonds generate infinite 2D networks. s2056989019011253

Chadeayne and colleagues published the crystal structure of 4-HO-MiPT fumarate monohydrate in 2019, followed by a second crystalline form — the bis(miprocinium) fumarate salt — in 2020supported

Crystal structure of 4-HO-MiPT fumarate salt. Tryptammonium and fumarate ions in 1D chains via hydrogen bonds. s2056989020002923

In 2021, Klein et al. conducted a structure-activity relationship study of psilocybin analogs encompassing the 4-AcO/4-HO tryptamine class, and Gatch et al. examined discriminative stimulus properties of substituted tryptamines in rats, establishing that 4-hydroxy forms are consistently more potent than 4-acetoxy counterparts.supported

SAR of 17 tryptamines with 4-hydroxy or 4-acetoxy groups and symmetrical/asymmetrical N,N-dialkyl substituents. acsptsci.0c00176

In 2021, Klein et al. conducted a structure-activity relationship study of psilocybin analogs encompassing the 4-AcO/4-HO tryptamine class, and Gatch et al. examined discriminative stimulus properties of substituted tryptamines in rats, establishing that 4-hydroxy forms are consistently more potent than 4-acetoxy counterparts.supported

4-hydroxy compounds more potent than 4-acetoxy. 4-OH-MET (4-HO-MET) fully substituted for DOM discriminative stimulus in rats. acsptsci.0c00173

The pivotal dataset appeared in 2023, when Kozell et al. published the first binding affinity and functional potency data measured directly for 4-AcO-MiPT and 4-OH-MiPT at 5-ht2a, 5-ht2c, 5-ht1a, and serotonin-transportersupported

21 substituted tryptamines at 5-HT1A, 5-HT2A, 5-HT2C and SERT. jpet.122.001454

In the same year, Wallach et al. identified Gq-pathway signaling as the key predictor of psychedelic potential across the tryptamine classsupported

5-HT2A-Gq (not beta-arrestin2) efficacy predicts psychedelic potential via head-twitch response magnitude in mice. s41467-023-44016-1

Claim in history — inconclusiveinconclusiveworking →

Chadeayne and colleagues published the crystal structure of 4-HO-MiPT fumarate monohydrate in 2019, followed by a second crystalline form — the bis(miprocinium) fumarate salt — in 2020supported

Solid-state crystal structures of MiPT fumarate and 4-HO-MiPT fumarate monohydrate. s2056989019011253

Chadeayne and colleagues published the crystal structure of 4-HO-MiPT fumarate monohydrate in 2019, followed by a second crystalline form — the bis(miprocinium) fumarate salt — in 2020supported

Crystal structure of 4-HO-MiPT fumarate salt. Tryptammonium and fumarate ions in 1D chains via hydrogen bonds. s2056989020002923

In 2021, Klein et al. conducted a structure-activity relationship study of psilocybin analogs encompassing the 4-AcO/4-HO tryptamine class, and Gatch et al. examined discriminative stimulus properties of substituted tryptamines in rats, establishing that 4-hydroxy forms are consistently more potent than their 4-acetoxy counterparts.supported

SAR of 17 tryptamines with 4-hydroxy or 4-acetoxy groups and symmetrical/asymmetrical N,N-dialkyl substituents. acsptsci.0c00176

In 2021, Klein et al. conducted a structure-activity relationship study of psilocybin analogs encompassing the 4-AcO/4-HO tryptamine class, and Gatch et al. examined discriminative stimulus properties of substituted tryptamines in rats, establishing that 4-hydroxy forms are consistently more potent than their 4-acetoxy counterparts.supported

4-hydroxy compounds more potent than 4-acetoxy. acsptsci.0c00173

Claim in history — inconclusiveinconclusiveworking →

In the same year, Wallach et al. identified Gq-pathway signaling as the key predictor of psychedelic potential across the tryptamine classsupported

5-HT2A-Gq (not beta-arrestin2) efficacy predicts psychedelic potential via head-twitch response magnitude in mice. s41467-023-44016-1

Claim in history — inconclusiveinconclusiveworking →

Malaca et al. (2022) incubated 4-AcO-DiPT with human hepatocytes and identified the 4-hydroxy metabolite as the primary product, with additional formation of glucuronide and sulfate conjugates, an N-oxide, and an N-dealkylated species — six metabolites totalsupported

4-AcO-DiPT metabolism in human hepatocytes. Primary metabolite via ester hydrolysis is 4-OH-DiPT. Phase II: glucuronidation and sulfation. N-oxidation and N-dealkylation also occur. 6 metabolites identified. metabo12080705

By structural analogy, 4-AcO-MiPT is expected to undergo analogous ester hydrolysis to yield 4-OH-MiPT as the primary active metabolite, with subsequent phase I (N-dealkylation, N-oxidation) and phase II (glucuronidation, sulfation) transformationssupported

4-AcO-DiPT metabolism in human hepatocytes. Primary metabolite via ester hydrolysis is 4-OH-DiPT. Phase II: glucuronidation and sulfation. N-oxidation and N-dealkylation also occur. metabo12080705

Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →

The following parameters are drawn from psilocin (4-OH-DMT), the closest well-characterized structural-analog of 4-OH-MiPT, as reported in a systematic review of 112 human subjects:supported

Systematic review of 14 psilocybin PK studies (8 lab, 6 clinical; 112 healthy humans). pharmaceutics17040411

Within the broader SAR series, 4-AcO-DiPT — bearing N,N-diisopropyl groups — produces notably longer-lasting effects than dimethyl analogs, suggesting that increased N-alkyl bulk may slow metabolic inactivation. 4-AcO-MiPT, with its asymmetric methyl/isopropyl pattern, may occupy an intermediate position in this duration-metabolism relationship.supported

4-HO-DiPT and 4-AcO-DiPT produced longer-lasting effects than other compounds. acsptsci.0c00176

By structural analogy to psilocin, CYP2D6 and cyp3a4 are the presumed primary metabolic enzymes for 4-OH-MiPTsupported

Primary metabolism by CYP2D6 and CYP3A4; secondary MAO-A. pharmaceutics17040411

Malaca et al. (2022) incubated 4-AcO-DiPT with human hepatocytes and identified the 4-hydroxy metabolite as the primary product, with additional formation of glucuronide and sulfate conjugates, an N-oxide, and an N-dealkylated species — six metabolites totalsupported

4-AcO-DiPT metabolism in human hepatocytes. Primary metabolite via ester hydrolysis is 4-OH-DiPT. Phase II: glucuronidation and sulfation. N-oxidation and N-dealkylation also occur. 6 metabolites identified. metabo12080705

By structural analogy, 4-AcO-MiPT is expected to undergo analogous ester hydrolysis to yield 4-OH-MiPT as the primary active metabolite, with subsequent phase I (N-dealkylation, N-oxidation) and phase II (glucuronidation, sulfation) transformationssupported

4-AcO-DiPT metabolism in human hepatocytes. Primary metabolite via ester hydrolysis is 4-OH-DiPT. Phase II: glucuronidation and sulfation. N-oxidation and N-dealkylation also occur. metabo12080705

Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →

The following parameters are drawn from psilocin (4-OH-DMT), the closest well-characterized structural-analog of 4-OH-MiPT, as reported in a systematic review of 112 human subjects:supported

Systematic review of 14 psilocybin PK studies (8 lab, 6 clinical; 112 healthy humans). pharmaceutics17040411

Within the broader SAR series, 4-AcO-DiPT — bearing N,N-diisopropyl groups — produces notably longer-lasting effects than dimethyl analogs, suggesting that increased N-alkyl bulk may slow metabolic inactivation. 4-AcO-MiPT, with its asymmetric methyl/isopropyl pattern, may occupy an intermediate position in this duration-metabolism relationship.supported

4-HO-DiPT and 4-AcO-DiPT produced longer-lasting effects than other compounds. acsptsci.0c00176

By structural analogy to psilocin, CYP2D6 and cyp3a4 are the presumed primary metabolic enzymes for 4-OH-MiPTsupported

Primary metabolism by CYP2D6 and CYP3A4; secondary MAO-A. pharmaceutics17040411

Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

Wallach et al. (2023) demonstrated across the tryptamine class that Gq-biased agonism — rather than beta-arrestin2 recruitment — is the signaling pathway predicting psychedelic head-twitch response, and that beta-arrestin-biased ligands instead induce downregulation and tachyphylaxissupported

5-HT2A-Gq (not beta-arrestin2) efficacy predicts psychedelic potential via head-twitch response magnitude in mice. Beta-arrestin-biased ligands block psychedelic effects and induce receptor downregulation and tachyphylaxis. s41467-023-44016-1

Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

Wallach et al. (2023) demonstrated across the tryptamine class that Gq-biased agonism — rather than beta-arrestin2 recruitment — is the signaling pathway predicting psychedelic head-twitch response, and that beta-arrestin-biased ligands instead induce downregulation and tachyphylaxissupported

5-HT2A-Gq (not beta-arrestin2) efficacy predicts psychedelic potential via head-twitch response magnitude in mice. Beta-arrestin-biased ligands block psychedelic effects and induce receptor downregulation and tachyphylaxis. s41467-023-44016-1

Claim in summary — inconclusiveinconclusiveworking →

Claim in summary — inconclusiveinconclusiveworking →

Gq-pathway signaling at 5-HT₂A, rather than beta-arrestin2 recruitment, predicts psychedelic potential in this compound class.supported

5-HT2A-Gq (not beta-arrestin2) efficacy predicts psychedelic potential via head-twitch response magnitude in mice. s41467-023-44016-1

No LD₅₀ data exist for 4-AcO-MiPT in any species, and no adverse event case reports specific to this compound have been published. tolerance develops rapidly via 5-HT₂A downregulation, with community consensus suggesting full reset within approximately 7 dayspartially supported

Beta-arrestin-biased ligands block psychedelic effects and induce receptor downregulation and tachyphylaxis. s41467-023-44016-1

Co-administration with serotonergic agents — particularly MAOIs and tramadol — carries mechanistically supported serotonin-syndrome risksupported

Evaluates drug-drug interaction risks and serotonin toxicity between psychedelic serotonergic substances and SSRIs. Important for MDMA-SSRI and MDMA-MAOI interaction assessment. s00213-021-05876-x

Claim in summary — inconclusiveinconclusiveworking →

Gq-pathway signaling at 5-HT₂A, rather than beta-arrestin2 recruitment, predicts psychedelic potential in this compound class.supported

5-HT2A-Gq (not beta-arrestin2) efficacy predicts psychedelic potential via head-twitch response magnitude in mice. s41467-023-44016-1

Claim in summary — inconclusiveinconclusiveworking →

Co-administration with serotonergic agents — particularly MAOIs and tramadol — carries mechanistically supported serotonin-syndrome risksupported

Evaluates drug-drug interaction risks and serotonin toxicity between psychedelic serotonergic substances and SSRIs. Important for MDMA-SSRI and MDMA-MAOI interaction assessment. s00213-021-05876-x

Claim in summary — inconclusiveinconclusiveworking →

The quantitative relationship between 4-AcO-MiPT and its hydrolysis product 4-OH-mipt provides the clearest evidence for the prodrug mechanism:supported

21 substituted tryptamines at 5-HT1A, 5-HT2A, 5-HT2C and SERT. 4-substituted compounds show high selectivity for 5-HT2AR. jpet.122.001454

Claim in comparative-pharmacology — inconclusiveinconclusiveworking →

Gatch et al. (2021) demonstrated that across the 4-substituted tryptamine series, 4-hydroxy compounds consistently produce drug-appropriate responding at lower doses than their 4-acetoxy counterparts in a dom-generalization paradigm in rats, confirming the prodrug relationship as a class-wide phenomenon rather than a feature unique to 4-AcO-MiPT.supported

4-hydroxy compounds more potent than 4-acetoxy. 4-OH-MET (4-HO-MET) fully substituted for DOM discriminative stimulus in rats. acsptsci.0c00173

Klein et al. (2021) systematically evaluated 17 tryptamines with 4-hydroxy or 4-acetoxy substitutions and varied N,N-dialkyl groups in mouse head-twitch response and 5-HT₂A/2B/2C functional assayssupported

SAR of 17 tryptamines with 4-hydroxy or 4-acetoxy groups and symmetrical/asymmetrical N,N-dialkyl substituents. 4-HO-DiPT ED50=3.46 μmol/kg in mouse head-twitch response. All compounds full/partial agonists at 5-HT2A/2B/2C. acsptsci.0c00176

The quantitative relationship between 4-AcO-MiPT and its hydrolysis product 4-OH-mipt provides the clearest evidence for the prodrug mechanism:supported

21 substituted tryptamines at 5-HT1A, 5-HT2A, 5-HT2C and SERT. 4-substituted compounds show high selectivity for 5-HT2AR. jpet.122.001454

Claim in comparative-pharmacology — inconclusiveinconclusiveworking →

Gatch et al. (2021) demonstrated that across the 4-substituted tryptamine series, 4-hydroxy compounds consistently produce drug-appropriate responding at lower doses than their 4-acetoxy counterparts in a dom-generalization paradigm in rats, confirming the prodrug relationship as a class-wide phenomenon rather than a feature unique to 4-AcO-MiPT.supported

4-OH-MET (4-HO-MET) fully substituted for DOM discriminative stimulus in rats. 4-hydroxy compounds more potent than 4-acetoxy. acsptsci.0c00173

Klein et al. (2021) systematically evaluated 17 tryptamines with 4-hydroxy or 4-acetoxy substitutions and varied N,N-dialkyl groups in mouse head-twitch response and 5-HT₂A/2B/2C functional assayssupported

SAR of 17 tryptamines with 4-hydroxy or 4-acetoxy groups and symmetrical/asymmetrical N,N-dialkyl substituents. 4-HO-DiPT ED50=3.46 μmol/kg in mouse head-twitch response. All compounds full/partial agonists at 5-HT2A/2B/2C. acsptsci.0c00176

This N-alkyl pattern places 4-AcO-MiPT structurally between the more compact 4-aco-dmt (N,N-dimethyl) and the bulkier 4-aco-dipt (N,N-diisopropyl) in the structure-activity relationship space of psilocybin analogs.supported

SAR of 17 tryptamines with 4-hydroxy or 4-acetoxy groups and symmetrical/asymmetrical N,N-dialkyl substituents. acsptsci.0c00176

Chadeayne et al. (2019) determined the crystal structure of 4-HO-MiPT fumarate as a monohydrate, identifying N–H···O and O–H···O hydrogen bonds forming infinite two-dimensional networkssupported

Solid-state crystal structures of MiPT fumarate and 4-HO-MiPT fumarate monohydrate. N-H...O and O-H...O hydrogen bonds generate infinite 2D networks. s2056989019011253

A second crystalline form — the bis(miprocinium) fumarate salt — was reported in 2020supported

Crystal structure of 4-HO-MiPT fumarate salt. Tryptammonium and fumarate ions in 1D chains via hydrogen bonds. s2056989020002923

This N-alkyl pattern places 4-AcO-MiPT structurally between the more compact 4-aco-dmt (N,N-dimethyl) and the bulkier 4-aco-dipt (N,N-diisopropyl) in the structure-activity relationship space of psilocybin analogs.supported

SAR of 17 tryptamines with 4-hydroxy or 4-acetoxy groups and symmetrical/asymmetrical N,N-dialkyl substituents. acsptsci.0c00176

Chadeayne et al. (2019) determined the crystal structure of 4-HO-MiPT fumarate as a monohydrate, identifying N–H···O and O–H···O hydrogen bonds forming infinite two-dimensional networkssupported

Solid-state crystal structures of MiPT fumarate and 4-HO-MiPT fumarate monohydrate. Both cations feature side-chain disorder. N-H...O and O-H...O hydrogen bonds generate infinite 2D networks. s2056989019011253

A second crystalline form — the bis(miprocinium) fumarate salt — was reported in 2020supported

Crystal structure of 4-HO-MiPT fumarate salt. Tryptammonium and fumarate ions in 1D chains via hydrogen bonds. s2056989020002923

All mechanistic discussion below is extrapolated from the serotonergic psychedelic class and the compound's established 5-ht2a partial-agonist pharmacology.supported

4-substituted compounds show high selectivity for 5-HT2AR. jpet.122.001454

Claim in neuroscience — inconclusiveinconclusiveworking →

Downstream of 5-HT₂A activation, serotonergic psychedelics engage nmda-receptor and ampa-receptor glutamate receptor modulation and activate mTOR-bdnf-TrkB neuroplasticity cascades, effects that may underlie the persisting psychological changes reported after acute psychedelic experiencessupported

Reviews neurobiological therapeutic mechanisms via 5-HT2A/5-HT1A and NMDA/AMPA; neuroplasticity via mTOR, BDNF. pharmrev.120.000056

All mechanistic discussion below is extrapolated from the serotonergic psychedelic class and the compound's established 5-ht2a partial-agonist pharmacology.supported

21 substituted tryptamines at 5-HT1A, 5-HT2A, 5-HT2C and SERT. 4-substituted compounds show high selectivity for 5-HT2AR. jpet.122.001454

Claim in neuroscience — inconclusiveinconclusiveworking →

Downstream of 5-HT₂A activation, serotonergic psychedelics engage nmda-receptor and ampa-receptor glutamate receptor modulation and activate mTOR-bdnf-TrkB neuroplasticity cascades, effects that may underlie the persisting psychological changes reported after acute psychedelic experiencessupported

Reviews neurobiological therapeutic mechanisms via 5-HT2A/5-HT1A and NMDA/AMPA; neuroplasticity via mTOR, BDNF; immunomodulation; neurotransmitter modulation. pharmrev.120.000056

Claim in clinical-evidence — inconclusiveinconclusiveworking →

Claim in clinical-evidence — inconclusiveinconclusiveworking →