Chemistry:MBL-61

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MBL-61, or MOB-61, also known as 1-methyl-2-bromo-LSD, is a serotonin receptor modulator of the lysergamide family related to lysergic acid diethylamide (LSD).[1][2][3][4][5] It is the 1-methyl derivative of 2-bromo-LSD (BOL-148).[1][2][3][5] Extensive metabolism of other 1-methylated lysergamides to their secondary amine derivatives, for instance methysergide (1-methylmethylergometrine) conversion into methylergometrine, has been observed.[6][7] Similarly to the case of 2-bromo-LSD, MBL-61 was inactive as a psychedelic in humans at doses of up to 10 to 14 mg orally.[3][8][9][1][4][5] However, whereas 2-bromo-LSD can reportedly still produce some hallucinogenic effects at high doses, such effects are said to be completely lost in the case of MBL-61.[1] In any case, both drugs are still potent serotonin receptor modulators like LSD, with MBL-61 having 5.3-fold the antiserotonergic activity of LSD in vitro and the highest degree of antiserotonergic activity of any other assessed lysergamide.[3][1][4][10][5][11] MBL-61 was first described in the scientific literature by Albert Hofmann and colleagues in 1957.[2][12]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 "Some Compounds With Hallucinogenic Activity". Ergot Alkaloids and Related Compounds. Handbook of Experimental Pharmacology (HEP). 49. Berlin, Heidelberg: Springer Berlin Heidelberg. 1978. pp. 567–614. doi:10.1007/978-3-642-66775-6_8. ISBN 978-3-642-66777-0. https://bibliography.maps.org/resources/download/8769#page=30. "1-Methyl-2-bromo-LSD (MBL61, No. 37b) was expected to combine the effects of the two ring substitutions. Actually, the psychotomimetic property seems to be completely lost (ISBELL et al., 1959a), whereas the antiserotonin activity on the isolated rat uterus surpasses that of the 1-methyl (370%) and of the 2-bromo (100%) derivatives and amounts to 530% of the LSD effect (CERLETTI and DOEPFNER, 1958a); on the rat paw edema, however, it is only 26% as active as LSD (DOEPFNER and CERLETTI, 1958). It is not pyretogenic in the rabbit (Sandoz Res. Lab., 1958). [...] By substitution in position 2 with a bromine atom, on the other hand, the psychotomimetic effect is nearly (BOL 148) or completely (MBL61) suppressed." 
  2. ↑ 2.0 2.1 2.2 "Chemical Background". Ergot Alkaloids and Related Compounds. Handbook of Experimental Pharmacology (HEP). 49. Berlin, Heidelberg: Springer Berlin Heidelberg. 1978. pp. 29–85. doi:10.1007/978-3-642-66775-6_2. ISBN 978-3-642-66777-0. 
  3. ↑ 3.0 3.1 3.2 3.3 Shulgin, Alexander; Shulgin, Ann (September 1997). TiHKAL: The Continuation. Berkeley, California: Transform Press. ISBN 0-9630096-9-9. OCLC 38503252. http://www.erowid.org/library/books_online/tihkal/tihkal.shtml.  https://www.erowid.org/library/books_online/tihkal/tihkal26.shtml "BOL-148. 2-Bromo-N,N-diethyllysergamide. This synthetic ergot derivative, along with its 1-methyl homologue MBL-61 (mentioned below) should be used as powerful tools for studying the mechanism of action of LSD in the human animal. It does not have LSD-like effects in man. At 6 to 10 milligrams orally, there are some mental changes noted. But in another study, 20 milligrams was administered a day to a subject for 7 days, and there were no reported effects. And yet it is as potent a serotonin agonist as is LSD. How can serotonin be argued as a neurotransmitter that is a major player in explaining the action of psychedelic drugs, when this compound is nearly without activity. [...] MBL-61. 2-Bromo-N,N-diethyl-1-methyllysergamide. This is the compound BOL-148 (mentioned above) with a methyl group attached to the 1-position of the indole ring (LSD has a hydrogen there). This would be an even more tantalizing challenge to the serotonin theory for central activity of the psychedelics, in that it is without any activity in man at an oral dose of 14 milligrams (similar to the inactivity of the BOL-61 compound, but it is some five times more potent as a serotonin agonist. 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).
  4. ↑ 4.0 4.1 4.2 "D-Lysergic acid diethylamide (LSD): A review of its present status". Clinical Pharmacology and Therapeutics 6 (2): 183–255. 1965. doi:10.1002/cpt196562183. PMID 14288188. 
  5. ↑ 5.0 5.1 5.2 5.3 "Relationships of psychotomimetic to anti-serotonin potencies of congeners of lysergic acid diethylamide (LSD-25)". Psychopharmacologia 1: 20–28. 1959. doi:10.1007/BF00408108. PMID 14405872. 
  6. ↑ "Multipotent and Poly-therapeutic Fungal Alkaloids of Claviceps purpurea". Medicinal Plants and Fungi: Recent Advances in Research and Development. Medicinal and Aromatic Plants of the World. 4. 2017. pp. 229–252. doi:10.1007/978-981-10-5978-0_8. ISBN 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." 
  7. ↑ "Methylergometrine, an active metabolite of methysergide". Cephalalgia 6 (1): 35–41. March 1986. doi:10.1046/j.1468-2982.1986.0601035.x. PMID 3698092. 
  8. ↑ "Basic Pharmacology and Effects". Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. 2003. pp. 67–137. ISBN 978-0-12-433951-4. https://web.archive.org/web/20250223164514/https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=6bb3a7499da8e9852b39cd4db16891147c83f5c6. 
  9. ↑ "Structure-activity relationships of the classic hallucinogens and their analogs". NIDA Research Monograph 146: 74–91. 1994. PMID 8742795. 
  10. ↑ "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. doi:10.1016/S0022-3565(25)11933-2. PMID 13502837. https://bibliography.maps.org/resources/download/19096. "So far the combined substitution of a methyl group and a bromine atom in positions 1 and 2, respectively, has yielded the most potent compound (MOB-61) with an activity 5.3 times that of LSD. Further studies with this interesting derivative are presently under way.". 
  11. ↑ "Comparison of lysergic acid derivatives and antihistamines as inhibitors of the edema provoked in the rat's paw by serotonin". International Archives of Allergy and Applied Immunology 12 (1–2): 89–97. 1958. doi:10.1159/000228445. PMID 13549054. 
  12. ↑ "Substitutionen am Ringsystem der Lysergsäure. III. Halogenierung. 45. Mitteilung über Mutterkornalkaloide". Helvetica Chimica Acta 40 (7): 2160–2170. 1957. doi:10.1002/hlca.19570400716. ISSN 0018-019X. Bibcode: 1957HChAc..40.2160T. 



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