1-Methyl-2-iodo-LSD

vanc 6 1-Methyl-2-iodo-LSD.svg skin-invert-image 175px MIL 3D.png bg-transparent 200px Serotonin receptor modulator None 97165-34-9 126269 112233 MIL; 1-Me-2-I-LSD; 2-Iodo-1-methyl-N,N-diethyllysergamide (6aR,9R)-N,N-diethyl-5-iodo-4,7-dimethyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide 21 26 1 3 1 CCN(CC)C(=O)[C@H]1CN([C@@H]2CC3=C(N(C4=CC=CC(=C34)C2=C1)C)I)C 1S/C21H26IN3O/c1-5-25(6-2)21(26)13-10-15-14-8-7-9-17-19(14)16(20(22)24(17)4)11-18(15)23(3)12-13/h7-10,13,18H,5-6,11-12H2,1-4H3/t13-,18-/m1/s1 TWQOQCUIXUGDKO-FZKQIMNGSA-N 1-Methyl-2-iodo-LSD (MIL) is a serotonin receptor modulator of the lysergamide family related to lysergic acid diethylamide (LSD). 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 Table 3.23 Amide analogues and pyrrole derivatives of LSD [...] common name: 1-methyl-2-iodo-LSD [...] code: MIL [...] potency (mg): ?c, x-LSD: ? [...] c often used in human 11C PET scanning; activity unknown LSD-25 https://www.erowid.org/library/books_online/tihkal/tihkal26.shtml With it, as with the iodinated analogue MIL, there are many examples of the compromising of scientific integrity in the quest for funds and recognition. Both compounds are as effective as LSD itself in displacing labelled LSD that is bound to the post-synaptic serotonin receptor sites in animal brains. But neither of them show any LSD-like activity. But both have been labelled with 11C or 122I to give positron emitting forms that can be administered to man and localized in a positron emission tomography instrument (a PET scanner). 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. It is the 1-methyl derivative of 2-iodo-LSD (IOL). Extensive metabolism of other 1-methylated lysergamides to their secondary amine derivatives, for instance methysergide (1-methylmethylergometrine) conversion into methylergometrine, has been observed. Majrashi M, Ramesh S, Deruiter J, Mulabagal V, Pondugula S, Clark R, Dhanasekaran M Agrawal DC, Tsay HS, Shyur LF, Wu YC, Wang SY Multipotent and Poly-therapeutic Fungal Alkaloids of Claviceps purpurea Medicinal Plants and Fungi: Recent Advances in Research and Development 4 229–252 2017 10.1007/978-981-10-5978-0_8 Medicinal and Aromatic Plants of the World 2352-6831 978-981-10-5977-3 Metabolites of methysergide also exhibit pharmacological activity. Methylergometrine (one of methysergide’s metabolites) is responsible for methysergide’s therapeutic effects regarding migraine treatment (Müller-Schweinitzer and Tapparelli 1986). [...] The systemic availability of methysergide after oral administration is only 13%, due to a high degree of first-pass metabolism by N-1 demethylation to methylergometrine. After oral administration, the plasma concentrations of the metabolite are considerably higher than those of the parent drug, and the area under the plasma concentration curve (AUC) for methylergometrine is more than ten times greater than for methysergide. Müller-Schweinitzer E, Tapparelli C Methylergometrine, an active metabolite of methysergide Cephalalgia 6 1 35–41 March 1986 3698092 10.1046/j.1468-2982.1986.0601035.x 5778173 The properties and effects of MIL in humans are unknown. However, a radiolabeled form of MIL, 1-methyl-2-[125I]iodo-LSD ([125I]-MIL), as well as the analogue 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 26 9 2451 April 2021 33922330 8122807 10.3390/molecules26092451 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. [...] free Hoffman BJ, Karpa MD, Lever JR, Hartig PR N1-methyl-2-[125I]LSD ([125I]MIL), a preferred ligand for serotonin 5-HT2 receptors European Journal of Pharmacology 110 1 147–148 March 1985 4007051 10.1016/0014-2999(85)90043-3 Hoffman BJ, Scheffel U, Lever JR, Karpa MD, Hartig PR N1-methyl-2-125I-lysergic acid diethylamide, a preferred ligand for in vitro and in vivo characterization of serotonin receptors Journal of Neurochemistry 48 1 115–124 January 1987 3794694 10.1111/j.1471-4159.1987.tb13135.x [125I]-MIL has much greater selectivity for serotonin 5-HT2 receptors over dopamine receptors compared to LSD. MIL and [125I]-MIL were first described in the scientific literature by Beth J. Hoffman and colleagues by 1985. See also Substituted lysergamide 2-Iodo-LSD MBL-61 (1-methyl-2-bromo-LSD) BOL-148 (2-bromo-LSD) 1P-BOL-148 MLD-41 (1-methyl-LSD) Methysergide References External links 2-Iodo-1-methyl-LSD (MIL) - Isomer Design LSD-25 (Discusses MIL) - TiHKAL - Erowid LSD-25 (Discusses MIL) - TiHKAL - Isomer Design Category:Diethylamides Category:Iodoarenes Category:Lysergamides Category:Methyl compounds Category:Serotonin receptor modulators