 | |
| Clinical data | |
|---|---|
| Other names | 4-Isobutyl-2,5-dimethoxyphenethylamine; 2,5-Dimethoxy-4-isobutylphenethylamine; 2C-iBu; 2C-IB; ELE-02; ELE02; ELEU02 |
| Routes of administration | Oral,[1]ophthalmic[2][3] |
| Drug class | Serotonin5-HT2A receptoragonist;Serotonergic psychedelic;Hallucinogen;Anti-inflammatory drug |
| Pharmacokinetic data | |
| Protein binding | 74%[4] |
| Duration of action | 20 hours[1] |
| Identifiers | |
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| PubChemCID | |
| Chemical and physical data | |
| Formula | C14H23NO2 |
| Molar mass | 237.343 g·mol−1 |
| 3D model (JSmol) | |
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2C-iBu, or2C-IB, also known as4-isobutyl-2,5-dimethoxyphenethylamine or by its developmental code nameELE-02, is aserotonin5-HT2A receptoragonist,serotonergic psychedelic, andanti-inflammatory drug which is under development for the treatment ofinflammation.[2][3][4][5][6][7] It is a member of thephenethylamine and2C families ofcompounds.[4][5][7] The drug is being developed as atopicaleye drop for treatment ofinflammatoryeye conditions.[2][3] There is also interest in 2C-iBu and related drugs for treatment of systemicinflammation andneuroinflammation.[8][9][10][11][12][5]
2C-iBu was not assessed or discovered byAlexander Shulgin and was not described in his 1991 bookPiHKAL (Phenethylamines I Have Known and Loved).[7][13] However, he did include 2C-iBu (as "2C-IB") as aDOManalogue in a table in his 2011 bookThe Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds.[1] In addition, Shulgin stated in a footnote that a 5 mgoral dose of 2C-iBu produces threshold activity and has a longduration of about 20 hours.[1] The cited source for these observations was a 2006 personal communication with M. Mueller.[1]
| Target | Affinity (Ki, nM) | |
|---|---|---|
| 2C-iBu | (R)-DOI | |
| 5-HT1A | 79 | 1,300 |
| 5-HT1B | 50 | 2,500 |
| 5-HT1D | 63 | ND |
| 5-HT2A | 1.3 | 0.040 |
| 5-HT2B | 16 | 2.5 |
| 5-HT2C | 0.25 | 0.63 |
| 5-HT6 | 1,300 | ND |
| 5-HT7 | 320 | ND |
| Notes: The smaller the value, the more avidly the drug interacts with the site. All proteins are human unless otherwise specified.Refs:[4] | ||
2C-iBu is a highlypotent and robustlyefficaciousserotonin5-HT2A receptoragonist.[4] ItsEC50Tooltip half-maximal effective concentration values are 1.3 nM forcalcium mobilization and 57.5 nM forβ-arrestin-2 recruitment, whereas itsEmaxTooltip maximal efficacy values are 103% for calcium mobilization and 77% for β-arrestin-2 recruitment relative to serotonin.[4] The drug showed higher potency and efficacy as a serotonin 5-HT2A receptor agonist than several other 2C drugs, including 2C-NP,2C-B,2C-I,2C-H, and2C-iP, whereas its activities were more comparable to or less than those of theDOx drugsDOIB,(R)-DOB,(R)-DOI, andDOiP.[4] 2C-iBu has also been assessed and found to bind to otherserotonin receptors, including the serotonin5-HT2C,5-HT2B,5-HT1B,5-HT1D,5-HT1A,5-HT7, and5-HT6 receptors, in that order ofaffinity and with varying avidities.[4]
2C-iBudose-dependently produces thehead-twitch response (HTR), a behavioral proxy of psychedelic effects, in rodents.[4] In terms ofED50Tooltip median effective dose, 2C-iBu is about 3-fold less potent than (R)-DOI in producing the HTR.[4] According to Eleusis, it is expected to have "greatly reduced"psychoactivity orhallucinogenic effects compared to related drugs like other members of the 2C family.[6][14]
The drug is effective in anallergicasthma model in rodents and showed similar potency as (R)-DOI.[4] Due to its reduced potency in producing the HTR but retained anti-inflammatory potency, 2C-iBu is expected to show greater separation between the desired anti-inflammatory and the undesired psychedelic effects in humans compared to (R)-DOI.[4] In contrast to certain other anti-inflammatory drugs likecorticosteroids, serotonin 5-HT2A receptor agonists like 2C-iBu are notimmunosuppressants.[14]
2C-iBu, also known as 4-isobutyl-2,5-dimethoxyphenethylamine, is aphenethylamine and2Cderivative.[4][5][7]
Thechemical synthesis of 2C-iBu has been described.[4][1]
Related drugs to 2C-iBu include2C-Bu (thebutylanalogue),2C-tBu (thetert-butyl analogue),2C-sBu (thesec-butyl analogue), and2C-CPM (thecyclopropylmethyl analogue).[4] In addition, 2C-iBu is related toDOx drugs such asDOIB (DOiBu).[4][15]
According toCharles D. Nichols,2,5-dimethoxyamphetamine (2,5-DMA) has potent anti-inflammatory activity with weak or no hallucinogenic effects.[7][15] Moreover,DOTFM has potent psychedelic effects with no anti-inflammatory activity.[7][16][17] Hence, it appears that the anti-inflammatory effects and psychedelic effects of serotonin 5-HT2A receptor agonists can be fully dissociated.[7]
2C-iBu was briefly described byAlexander Shulgin in his 2011 bookThe Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds.[1] It was subsequently more thoroughly characterized byCharles D. Nichols and colleagues atLouisiana State University School of Medicine as a novel anti-inflammatory drug in the late 2010s.[4][7]Eleusis has licensed 2C-iBuintellectual property from LSU and the drug has reached thepreclinical research stage of development, but no recent development has been reported as of October 2023.[2][3]
2C-iBu is not acontrolled substance in theUnited States as of 2020.[6]
2C-iBu was developed as a novelanti-inflammatory drug byCharles D. Nichols and colleagues atEleusis in the late 2010s.[7][4] They are developing it for treatment ofinflammatory conditions.[2][3] Eleusis was acquired by and merged intoBeckley Psytech in October 2022.[2][18][19] The drug has reached thepreclinical research stage of development, but no recent development has been reported as of October 2023.[2][3] Eleusis has licensedintellectual property surrounding 2C-iBu and haspatent protection for 2C-iBu.[6][4]
2c-IB: [...] (15) Synthesis (from 2,5-dimethoxyisobutylbenzene) (Mueller, 2006); although this compound was reported here, a structure-search in Chemical Abstracts does not produce a CAS registry number (16) Threshold activity in humans at 5 mg orally; long duration (about 20 hours; Mueller, 2006). [...] Mueller, M. (2006) Personal communication with A.T. Shulgin.
The nature of the 4-position substituent of phenethylamine psychedelics has been previously linked to 5-HT2 receptor selectivity as well as agonist properties at 5-HT2 receptors.40 Analysis of the 4-position demonstrated that the identity of the moiety at this position was rather flexible. Fully efficacious substitutions at the 4-position included the halogens iodine and bromine (R)-DOI (Figure 3), 2C-B (Figure 7A), methoxy (TMA-2) (Figure 7G), short-chain hydrocarbons (R)-DOM (Figure 7H), (R)-DOET) (Figure 7I), and a branched hydrocarbon (DOiBu) (Figure 7J). [...] In a comparison of PenH-AUC values determined for each drug as a proxy measure of anti-inflammatory efficacy (Figure 8A) to either EC50 or EMax for calcium mobilization downstream of 5- HT2A receptor activation (Table 1), [...]
The effects of (R)-DOTFM were examined in the head-twitch response (HTR) assay. (R)-DOTFM produced a strong HTR with a potent ED 50 of 0.60 μmol/kg. These values are equivalent to (R)-DOI, as previously determined.