1-Methyl-2-iodo-LSD

Pharmaceutical compound From Wikipedia, the free encyclopedia

1-Methyl-2-iodo-LSD (MIL) is a serotonin receptor modulator of the lysergamide family related to lysergic acid diethylamide (LSD).^[1]^[2] It is the 1-methyl derivative of 2-iodo-LSD (IOL).^[1]^[2] Extensive metabolism of other 1-methylated lysergamides to their secondary amine derivatives, for instance methysergide (1-methylmethylergometrine) conversion into methylergometrine, has been observed.^[3]^[4] The properties and effects of MIL in humans are unknown.^[1] 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.^[5]^[1]^[2]^[6]^[7] [¹²⁵I]-MIL has much greater selectivity for serotonin 5-HT₂ receptors over dopamine receptors compared to LSD.^[6]^[7] MIL and [¹²⁵I]-MIL were first described in the scientific literature by Beth J. Hoffman and colleagues by 1985.^[5]^[6]^[7]

Other namesMIL; 1-Me-2-I-LSD; 2-Iodo-1-methyl-N,N-diethyllysergamide

Drug classSerotonin receptor modulator

ATC code

None

CAS Number

97165-34-9

Quick facts Clinical data, Other names ...

1-Methyl-2-iodo-LSD
Clinical data


Other names	MIL; 1-Me-2-I-LSD; 2-Iodo-1-methyl-N,N-diethyllysergamide
Drug class	Serotonin receptor modulator
ATC code	None
Identifiers
IUPAC name (6aR,9R)-N,N-diethyl-5-iodo-4,7-dimethyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide
CAS Number	97165-34-9
PubChem CID	126269
ChemSpider	112233
CompTox Dashboard (EPA)	DTXSID10914083
Chemical and physical data
Formula	C₂₁H₂₆IN₃O
Molar mass	463.363 gÂ·mol^â1
3D model (JSmol)	Interactive image
SMILES CCN(CC)C(=O)[C@H]1CN([C@@H]2CC3=C(N(C4=CC=CC(=C34)C2=C1)C)I)C
InChI InChI=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 Key:TWQOQCUIXUGDKO-FZKQIMNGSA-N

References

[1]
Shulgin AT (2003). "Basic Pharmacology and Effects". In Laing RR (ed.). Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. pp. 67â137. ISBN 978-0-12-433951-4. 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
[2]
Shulgin A, Shulgin A (September 1997). TiHKAL: The Continuation. Berkeley, California: Transform Press. ISBN 0-9630096-9-9. OCLC 38503252. "LSD-25". 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.
[3]
Majrashi M, Ramesh S, Deruiter J, Mulabagal V, Pondugula S, Clark R, et al. (2017). "Multipotent and Poly-therapeutic Fungal Alkaloids of Claviceps purpurea". In Agrawal DC, Tsay HS, Shyur LF, Wu YC, Wang SY (eds.). Medicinal Plants and Fungi: Recent Advances in Research and Development. Medicinal and Aromatic Plants of the World. Vol. 4. pp. 229â252. doi:10.1007/978-981-10-5978-0_8. ISBN 978-981-10-5977-3. ISSN 2352-6831. Metabolites of methysergide also exhibit pharmacological activity. Methylergometrine (one of methysergide's metabolites) is responsible for methysergide's therapeutic effects regarding migraine treatment (MÃ¼ller-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.
[4]
MÃ¼ller-Schweinitzer E, Tapparelli C (March 1986). "Methylergometrine, an active metabolite of methysergide". Cephalalgia. 6 (1): 35â41. doi:10.1046/j.1468-2982.1986.0601035.x. PMID 3698092. S2CID 5778173.
[5]
Cumming P, Scheidegger M, Dornbierer D, Palner M, Quednow BB, Martin-Soelch C (April 2021). "Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans". Molecules. 26 (9): 2451. doi:10.3390/molecules26092451. PMC 8122807. PMID 33922330. 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. [...]
[6]
Hoffman BJ, Karpa MD, Lever JR, Hartig PR (March 1985). "N1-methyl-2-[125I]LSD ([125I]MIL), a preferred ligand for serotonin 5-HT2 receptors". European Journal of Pharmacology. 110 (1): 147â148. doi:10.1016/0014-2999(85)90043-3. PMID 4007051.
[7]
Hoffman BJ, Scheffel U, Lever JR, Karpa MD, Hartig PR (January 1987). "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): 115â124. doi:10.1111/j.1471-4159.1987.tb13135.x. PMID 3794694.

1-Methyl-2-iodo-LSD

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