2-Iodo-LSD

vanc 6 2-Iodo-LSD.svg skin-invert-image 200px Serotonin receptor modulator; Non-hallucinogenic serotonin 5-HT2A receptor modulator None 3712-25-2 151142 133214 433352 Iodo-LSD; Iodine-LSD; IOL; 2-Iodolysergic acid diethylamide; 2-Iodo-N,N-diethyllysergamide; N,N-Diethyl-2-iodo-6-methyl-9,10-didehydroergoline-8β-carboxamide (6aR,9R)-N,N-diethyl-5-iodo-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide 20 24 1 3 1 CCN(CC)C(=O)[C@H]1CN([C@@H]2CC3=C(NC4=CC=CC(=C34)C2=C1)I)C 1S/C20H24IN3O/c1-4-24(5-2)20(25)12-9-14-13-7-6-8-16-18(13)15(19(21)22-16)10-17(14)23(3)11-12/h6-9,12,17,22H,4-5,10-11H2,1-3H3/t12-,17-/m1/s1 OBCUQRYIGTWROI-SJKOYZFVSA-N 2-Iodo-LSD (IOL) is a putatively non-hallucinogenic serotonin receptor modulator of the lysergamide family related to 2-bromo-LSD (BOL-148) and lysergic acid diethylamide (LSD). Nichols DE Chemistry and Structure-Activity Relationships of Psychedelics Current Topics in Behavioral Neurosciences 36 1–43 2018 28401524 10.1007/7854_2017_475 978-3-662-55878-2 https://bitnest.netfirms.com/external/10.1007/7854_2017_475 If a halogen is introduced at the 2-position of LSD, for example in 2-bromo-LSD (BOL-148) or 2-iodo-LSD, the resulting molecules lack hallucinogenic activity and are antagonists at the 5-HT2A receptor. No work with BOL-148 has been reported since the early 1970s, but it was shown that it could block the effects of LSD in humans.(Ginzel and Mayer-Gross 1956) The radiolabeled 2-iodo congener, [125I] 2-iodo-LSD, has been employed as a radioligand for 5-HT2 family receptors (Hartig et al. 1983; Nakada et al. 1984; McKenna et al. 1989; Watts et al. 1994). More recently, BOL has shown efficacy in aborting and/or preventing cluster headaches (Karst et al. 2010). Nichols DE Structure–activity relationships of serotonin 5-HT 2A agonists Wiley Interdisciplinary Reviews: Membrane Transport and Signaling 1 5 559–579 2012 10.1002/wmts.42 2190-460X free https://psilosybiini.info/paperit/Structure-activity%20relationships%20of%20serotonin%205-HT2A%20agonists%20(Nichols,%202012).pdf Halogenation at the 2-position of LSD as in 2-bromo-LSD (BOL-148) or 2-iodo-LSD leads to molecules that are 5-HT2A antagonists. Although virtually no work has been done with BOL-148 since the early 1970s, it was demonstrated early on that it could block the effects of LSD in humans.26 [125I]2-Iodo-LSD has found application as a radioactive label for 5-HT2 family receptors.27–30 Halberstadt AL, Geyer MA Miller PM, Blume AW, Kavanagh DJ, Kampman KM, Bates ME, Larimer ME, Petry NM, De Witte P, Ball SA [Chapter 61:] Neuropharmacology of Lysergic Acid Diethylamide (LSD) and Other Hallucinogens Biological Research on Addiction: Comprehensive Addictive Behaviors and Disorders 2 625–635 2013 10.1016/b978-0-12-398335-0.00061-3 Elsevier 978-0-12-398335-0 https://bibliography.maps.org/resources/download/13531 https://web.archive.org/web/20250328202548/https://bibliography.maps.org/resources/download/13531 28 March 2025 There is a complete loss of activity if LSD is brominated or iodinated in the 2-position, and these substances (2-bromo-LSD and 2-iodo-LSD, respectively) act as 5-HT2A antagonists. Consistent with its antagonist activity, pretreatment with 2-bromo-LSD completely blocks the effects of subsequent LSD administration. It is the 2-iodo derivative of LSD. Use and effects According to Alexander Shulgin in his 1997 book TiHKAL (Tryptamines I Have Known and Loved), it is unknown whether 2-iodo-LSD has ever been tested in humans. https://erowid.org/library/books_online/tihkal/tihkal26.shtml "1-Hydroxymethyl-LSD, 1-dimethylaminomethyl-LSD and 2-iodo-LSD. These three additional compounds are shown here because they were described in a synthetic flurry that followed the discovery the activity of LSD. But at the moment I know neither their internal Sandoz codes nor if they had ever been explored in man. This is a kind of frustrating catch-all entry, in that the long index will send you here, and once here you realize that nothing is known. Well, at least the compounds are known, and perhaps there is something in the Sandoz vaults that might be interesting. I do not have access to them. [...] I was at a meeting of a NIDA study section a few years ago, where some one presented some findings with a group of subjects who were complaining of continuing mental problems allegedly due to LSD exposure. A chart was put up showing the outline of the brain showing the locations of the EEG foci that were observed in one of these subjects. Along side it was a PET scan showing the distribution of radioactive LSD in a subject. The purpose was to discuss the similarities and differences of the coordinates of electrical activity and radio-isotope concentration. I innocently asked what positron isotope had been used, as I did not know of any successful positron labelling of LSD. Carbon 11, I was told. Where in the molecule was the label incorporated, I asked. In the 1-position methyl group. It was finally acknowledged that the compound that had actually been used was 2-iodo-1-methyl-LSD, our MIL compound, which is quite a different world. A pharmacologist might say that they are similar in action (looking at serotonin, not psychedelic action), and a chemist might say they are of similar structure (looking at the upper 80% of the molecule. But they are different compounds. This is a most subtle form of deceit. It is, in fact, out and out dishonest, but it looks good up there on the screen at a lecture." Pharmacology Pharmacodynamics 2-Iodo-LSD shows high affinity for the serotonin 5-HT2 receptors and also shows affinity for other serotonin receptors as well as for the dopamine and adrenergic receptors. Glennon RA Higher-end serotonin receptors: 5-HT(5), 5-HT(6), and 5-HT(7) Journal of Medicinal Chemistry 46 14 2795–2812 July 2003 12825922 10.1021/jm030030n Middlemiss DN, Hibert M, Fozard JR Chapter 5. Drugs Acting at Central 5-Hydroxytryptamine Receptors Annual Reports in Medicinal Chemistry 21 41–50 1986 10.1016/s0065-7743(08)61115-x Elsevier 978-0-12-040521-3 https://linkinghub.elsevier.com/retrieve/pii/S006577430861115X 30 June 2025 In contrast to LSD, but similarly to 2-bromo-LSD, 2-iodo-LSD is predominantly antagonistic at the serotonin 5-HT2A and 5-HT2C receptors and is described as non-hallucinogenic. Glennon RA, Dukat M Serotonin receptors and their ligands: a lack of selective agents Pharmacology, Biochemistry, and Behavior 40 4 1009–1017 December 1991 1816555 10.1016/0091-3057(91)90121-h The drug has about 57.4% of the antiserotonergic activity of LSD in the isolated rat uterus in vitro, whereas 2-bromo-LSD has about 103% of LSD's potency in this assay. Cerletti A, Doepfner W Comparative study on the serotonin antagonism of amide derivatives of lysergic acid and of ergot alkaloids The Journal of Pharmacology and Experimental Therapeutics 122 1 124–136 January 1958 13502837 10.1016/S0022-3565(25)11933-2 Rothlin E Lysergic acid diethylamide and related substances Annals of the New York Academy of Sciences 66 3 668–676 March 1957 13425249 10.1111/j.1749-6632.1957.tb40756.x 1957NYASA..66..668R Hintzen A, Passie T The Pharmacology of LSD 19 10 June 2010 OUP/Beckley Foundation Press 978-0-19-958982-1 https://books.google.com/books?id=KTyC-e7NmI8C&pg=PA19 30 June 2025 2-Bromo-lysergic acid diethylamide (BOL-148) The most investigated lysergic acid derivative after LSD is bromo-LSD (BOL-148) (Table 2.3). Whilst the strength of serotonin antagonism with LSD is comparable, it possesses almost no psychic effects (even in doses up to 20 μg/kg). The only psychic effect described was a feeling of tiredness and some psychophysical irritation at high doses (Cerletti & Konzett, 1956). [...] Iodine-LSD is iodinated in position 2 and is only half as effective in relation to psychic effects, as well as to serotonin antagonism, as LSD itself (Cerletti & Konzett, 1956). [...] Radiolabeling [125I]2-Iodo-LSD, a radiolabeled analogue of 2-iodo-LSD, has been used as a radioligand for serotonin 5-HT2 receptors. Engel G, Müller-Schweinitzer E, Palacios JM 2-[125Iodo]LSD, a new ligand for the characterisation and localisation of 5-HT2 receptors Naunyn-Schmiedeberg's Archives of Pharmacology 325 4 328–336 April 1984 6728042 10.1007/BF00504377 In addition, radiolabeled derivatives of 2-iodo-LSD, such as 1-methyl-2-[125I]iodo-LSD ([125I]-MIL) and 1-ethyl-2-[125I]iodo-LSD ([125I]-EIL), have been developed for use as presumably non-hallucinogenic agents in imaging of serotonin receptors. Cumming P, Scheidegger M, Dornbierer D, Palner M, Quednow BB, Martin-Soelch C Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans Molecules Basel, Switzerland 26 9 2451 April 2021 33922330 8122807 10.3390/molecules26092451 free N-methyl-2-[125I]-iodo-lysergic acid diethylamide ([125I]-MIL, 24) was developed as a presumably non-hallucinogenic ligand for the molecular imaging of serotonin receptors, whereby N-methylation of [125I]-LSD (25) was intended to impart greater selectivity and sensitivity for 5HT2 receptors [23]. [...] D-(+)-N-ethyl-2-[125I]iodo-lysergic acid diethylamide ([125I]-EIL, 23) was developed as a ligand for molecular imaging of serotonin receptors. [...] Shulgin AT Laing RR Basic Pharmacology and Effects Hallucinogens: A Forensic Drug Handbook 67–137 2003 Elsevier Science Forensic Drug Handbook Series 978-0-12-433951-4 https://books.google.com/books?id=l1DrqgobbcwC https://web.archive.org/web/20250223164514/https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=6bb3a7499da8e9852b39cd4db16891147c83f5c6 History 2-Iodo-LSD was described in the scientific literature by Albert Hofmann and colleagues by 1956. Troxler F, Hofmann A Substitutionen am Ringsystem der Lysergsäure. III. Halogenierung. 45. Mitteilung über Mutterkornalkaloide Helvetica Chimica Acta 40 7 2160–2170 1957 10.1002/hlca.19570400716 1957HChAc..40.2160T 0018-019X https://onlinelibrary.wiley.com/doi/10.1002/hlca.19570400716 30 June 2025 subscription Cerletti A, Konzett H Spezifische Hemmung von 5-Oxytryptamin-Effekten durch Lysergsäurediäthylamid und ähnliche Körper Naunyn-Schmiedebergs Archiv für Experimentelle Pathologie und Pharmakologie 228 1–2 146–148 1956 13334586 10.1007/BF00259761 Specific inhibition of serotonin effects by lysergic acid diethylamide and similar compounds German Substitutionsprodukte des LSD 1. Acetyl-LSD, durch Einfiihrung eines Acetylrestes in 1-Stellung gewonnen, ist etwa 2mal starker 50T-hemmend wirksam. Brom- und Jod-LSD, durch Einffihrung von Brom und Jod in 2-Stellung bereitet, sind 1,5mal starker bzw. 2real schw~cher 50T-hemmend wirksam. Oxymethyl-LSD, durch Einffihrung einer 0xymethylgruppe in 1-Stellung gewonnen, ist 1,5mal schw~icher wirksam. See also Substituted lysergamide 2-Bromo-LSD (BOL-148) MBL-61 (1-methyl-2-bromo-LSD) 2-Oxo-LSD References External links 2-Iodo-LSD - Isomer Design LSD-25 (Discusses 2-Iodo-LSD) - TiHKAL - Erowid LSD-25 (Discusses 2-Iodo-LSD) - TiHKAL - Isomer Design Category:Diethylamides Category:Iodoarenes Category:Lysergamides Category:Serotonin receptor modulators