4-HO-MiPT

4-HO-MiPT (4-hydroxy-N-methyl-N-isopropyltryptamine; miprocin) is a synthetic indolylethylamine of the 4-hydroxytryptamine structural class, first synthesized by Repke, Grotjahn, and Shulgin in 1981 as part of a systematic exploration of N-alkylated 4-hydroxyindole derivatives [1]. The compound is a close structural analog of psilocin (4-HO-DMT), differing by replacement of the symmetrical N,N-dimethyl substitution with an asymmetric N-methyl-N-isopropyl arrangement that confers altered receptor selectivity, enhanced potency in behavioral assays, and moderate serotonin transporter (SERT) inhibitory activity not observed with the parent compound. Receptor binding studies have characterized 4-HO-MiPT as a high-affinity partial agonist at the serotonin 5-HT2A receptor (Ki approximately 113 nM; EC50 306 nM in inositol phosphate accumulation; Emax 74 percent of serotonin maximum), a full agonist at the 5-HT2C receptor (Ki 750 nM; EC50 261 nM; Emax 98 percent), a weak partial agonist at the 5-HT1A receptor (Ki 5870 nM; EC50 2590 nM; Emax 83 percent), and a moderate 5-HT2B receptor agonist (EC50 10.3 nM; Emax 49 percent) [2, 3]. At the serotonin transporter, 4-HO-MiPT displays substrate-like inhibition with a Ki of 483 nM and an uptake IC50 of 373 nM, representing approximately 7.5-fold greater SERT affinity than psilocin (Ki 3650 nM) and suggesting a dual serotonergic mechanism combining direct receptor agonism with monoamine reuptake modulation [2].

The pharmacological profile of 4-HO-MiPT positions it within the expanding library of psilocin analogs under investigation for serotonin receptor structure-activity relationships, biased agonism at 5-HT2 subtypes, and the mechanistic dissection of psychedelic-like behavioral responses in rodent models. In the mouse head-twitch response (HTR) assay, a validated behavioral proxy for 5-HT2A receptor activation, the compound produces dose-dependent responses with an ED50 of approximately 0.75 to 0.97 mg/kg, comparable to the other MiPT analogs (4-AcO-MiPT, 4-MeO-MiPT) despite substantial differences in in vitro receptor binding profiles [4]. The behavioral pharmacology, combined with the divergence between 5-HT2A binding affinity and functional potency and the moderate SERT interaction, makes 4-HO-MiPT a useful probe for investigating the contributions of receptor efficacy, transporter blockade, and pharmacokinetic disposition to in vivo serotonergic activity.

No pharmacokinetic studies have been published for 4-HO-MiPT in any species. Metabolism is inferred from structurally related 4-hydroxytryptamines to involve hepatic Phase I transformations including O-glucuronidation, O-sulfation, N-dealkylation (loss of the isopropyl or methyl group), and oxidative deamination, with cytochrome P450 enzymes and monoamine oxidase contributing to systemic clearance [5, 6]. The 4-hydroxyl substituent on the indole ring confers oxidative instability characteristic of the entire 4-hydroxytryptamine series; the compound discolors rapidly on exposure to air and light and requires storage under inert atmosphere at reduced temperature. Crystallographic characterization of the fumarate salt has been reported in two polymorphic forms by Chadeayne, Pham, Golen, and Manke (2019, 2020), providing definitive structural confirmation and a stable solid form for analytical and research applications [7, 8]. The compound is not a scheduled substance under United States federal law but is potentially prosecutable as an analog of psilocin under the Federal Analogue Act; it is a controlled substance in several other jurisdictions including the United Kingdom, Sweden, and Brazil. This monograph documents the chemistry, synthesis, receptor pharmacology, inferred pharmacokinetics, preclinical behavioral evidence, sourcing and handling considerations, stack interactions, adverse-event signals, and a structured comparative assessment against five related 4-hydroxytryptamine research compounds.