LSD (d-Lysergic acid diethylamide, "Acid")

Index

   Index ('round and 'round we go...) 
   Chemical Structure 
   Synonyms 
   Physical Properties 
   Scheduling 
   References 
      Psychopathology 
      Neuropharmacology 

Chemical Structure

              /CH2CH3   <-- this mess is attached to one of the chiral centers.
           CON              the leftmost hydrogen should go into the screen and
     H.   /   \CH2CH3       the amine should come out of the screen for d-LSD
       './____
        /     \
       /        N-CH3   <-- this nitrogen should be on the vertex of the ring
       \\      /            and is ASCII munged.
        \\____/_=H      <-- this hydrogen is on one of the chiral centers.
        /     \             it comes out of the screen for d-LSD, and should
       /       \            be attached to the vertex.
     /\\       /
    /  \\_____/
   ||   |    ||
   ||   |    ||
    \  //\   /
     \//  \ /
           N
           H
NOTE:
                N                      N        LSD could technically be
               /                      /         considered to be both a
         _____/                      /          phenethylamine and a
        /                            \          tryptamine.  It is almost
       /                              \         allways considered to be a
     /\\                    /\\       /         tryptamine.  There are rare
    /  \\                  /  \\_____/          ocassions, however, where it
   ||   |                 ||   |    ||          is referred to as being
   ||   |                 ||   |    ||          a phenethylamine and this
    \  //                  \  //\   /           is where the justification
     \//                    \//  \ /            for this classification
                                  N             comes from.
                                  H

  Phenethylamine             Tryptamine
    Structure                Structure

C20H25N3O 

Synonyms

Common Chemical Name: 
   d-Lysergic Acid Diethylamide 
Common Chemical Abbreviation: 
   LSD, LSD-25 
Chemical Abstracts: 
   Ergoline-8-carboxamide, 9,10-didehydro-N,N-diethyl-5-methyl- (8-beta) 

   [50-37-3] d-LSD
         

DEA Drug Control Numbers: 

   510: LSD (see 7315)
   520: LSD combinations (see 7350)
   7299: d-LSD Salt (unspecified)
   7300: Lysergic acid
   7301: Unknown lysergic acid and derivatives
   7302: DL Acetyl-LSD (sic) probably = d-1-ALD-52
   7303: DL Acetyl-lysergic acid monoethylamide (sic) probably = d-1-ALA-10
   7304: BOL-148
   7305: Dihydro-LSD
   7306: 2-Iodo-LSD
   7307: d-Iso-LSD
   7308: I-LSD
   7309: Lumi-d-LSD
   7310: Lysergic acid amide
   7311: d-Lysergic acid amylamide
   7312: d-Lysergic acid butylamide
   7313: d-Lysergic acid dibutylamide
   7314: d-LSD tartrate
   7315: d-LSD
   7316: l-LSD
   7317: d-Lysergic acid diisopropylamide
   7318: DAM-57
   7319: d-Lysergic acid dipropylamide
   7320: LAE-32
   7321: LEP-57
   7322: d-Lysergic acid heptylamide
   7323: d-Lysergic acid hexylamide
   7324: d-Lysergic acid methylamide
   7325: LME-54
   7326: d-Lysergic acid methylisopropylamide
   7327: d-Lysergic acid (beta)-methyl-(beta)-phenylethyl-isopropylamide
   7328: LMP-55
   7329: LSM-775
   7330: d-Lysergic acid piperidide
   7331: d-Lysergic acid propylamide
   7332: LPD-824
   7340: dl-Methyl-2-bromo-LSD (sic) probably = d-1-MBL-61
   7341: dl-Methyl-LSD (sic) probably = d-1-MLD-41
   7342: dl-Methyl lysergic acid monoethylamide (sic) probably = d-1-MLA-75
   7343: dl-Methyl lysergic acid pyrolidide (sic) probably = d-1-MPD-75
   7344: dl-Oxymethyl lysergic acid diethylamide (sic) probably = d-1-OML-632
   7345: d-LSD + other drugs
   7350: d-LSD + PCP


Edgewood Arsenel: 
Merck: 
   5507 (11th ed) "Lysergide" 
All Chemical Names: 
All Chemical Abbreviations: 
Unofficial/Street Names: 

Physical Properties

Melting Points: 
Index of Refraction: 

Scheduling

US: 
   Schedule I -- Officially named as a "depressant or stimulant substance", but listed under hallucinogenic substances. 
UK: 

Chemical Relatives

   Modifications to the ergoline ring: 
      2-Bromo-LSD (BOL-148) 
      2-Iodo-LSD 
      Dihydro-LSD 
      Lumi-LSD: formed by uv rad and hydrolysis at the 9-10 double bond. 
      Iso-LSD 
   Dialkyl-homologs of LSD: 
      d-Lysergic acid dimethylamide (DAM-57) 
      d-Lysergic acid methylethylamide (LME-54) 
      d-Lysergic acid methylpropylamide (LMP-55) 
      d-Lysergic acid methylisopropylamide 
      d-Lysergic acid (beta)-methyl-(beta)-phenethyl-isopropylamide 
      d-Lysergic acid dipropylamide 
      d-Lysergic acid diisopropylamide 
      d-Lysergic acid dibutylamide 
      d-Lysergic acid ethylpropylamide (LEP-57) 
      d-Lysergic acid pyrrolidide (LPD-824) 
      d-Lysergic acid piperidide 
      d-Lysergic acid morpholide (LSM-775) 
   Monoalkyl-homologs of LSD: 
      d-Lysergic acid methylamide 
      d-Lysergic acid ethylamide (LAE-32) 
      d-Lysergic acid propylamide 
      d-Lysergic acid butylamide 
      d-Lysergic acid amylamide 
      d-Lysergic acid hexylamide 
      d-Lysergic acid heptylamide 
   Substituents on the Indolic Nitrogen of LSD:
   NOTE: these have been writted as (for example) d-1-acetyl-LSD which mutates into d-l-acetyl-LSD which mutates into dl-LSD in the 'scientific' literature. They have also been incorrectly
   written as N-substituted-LSD rather than 1-substituted-LSD. N-Acetyl-LSD, for example, does not refer to ALD-52, but instead refers to N-Acetyl-N,N-diethyl-lysergic acid which only
   occurs in a parallel symmetry-broken universe where nitrogen has 4 valence electrons. 
      1-Oxymethyl-LSD (OML-632) 
      1-Methyl-LSD (MLD-41): this compound is converted to LSD in vivo 
      1-Methyl-2-bromo-LSD (MBL-61) 
      1-Methyl-lysergic acid monoethylamide (MLA-74) 
      1-Methyl-lysergic acid pyrolidide (MPD-75) 
      1-Acetyl-LSD (ALD-52): this compound is converted in LSD in vivo 
      1-Acetyl-lysergic acid monoethylamide (ALA-10) 
   Optical Isomers: 
      l-Lysergic acid 

References

Psychopathology

Abraham-HD, Aldridge-AM. "Adverse consequences of lysergic acid diethylamide." Addiction. Vol 88:1327-1334. 1993.

   Overview of acute effects, prolonged psychoses and post-hallucinogen perceptual disorder (PHPD). Biased somewhat towards trying to find problems with LSD and doesn't address the
   methodological considerations in the studies they cite. Interesting because it clearly states that LSD is not an in vivo clastogen, either weakly or not mutagenic, not teratogenic and not oncogenic
   (clastogen = breaks chromosomes, mutagen = causes DNA mutations, teratogenic = birth defects, oncogenic = causes cancer) -- and this got by the editors at Addictions. 

Neuropharmacology

Shen-Y, Monsma-FJ, Metcalf-MA, Jose-PA, Hamblin-MW, Sibley-DR, "Molecular Cloning and Expression of a 5-Hydroxytryptamine7 serotonin Receptor Subtype." Journal of Biological Chemistry. Vol
268(24):18200-18204. 25 Aug 1993.

   Discovery of a 5-HT7 receptor which has a high affinity for LSD (KD = 4.9 +/- 0.78 (n = 5) nM; Bmax = 5-15 pmol/mg protein). Also displays a high affinity for tricyclic antipsychotic and
   antidepressant agents. It is located primarily in the limbic and cortical regions of the brain.

Pierce-PA, Peroutka-SJ. "Antagonist Properties of d-LSD at 5-Hydroxytryptamine2 Receptors." Neuropsychopharmacology. Vol 3(5-6):503-508. 1990.

   Argues that LSD is a 5-HT2 receptor antagonist and that this tends to rule out the notion that classic hallucinogens work via a 5-HT2 agonist mechanism. Suggests that LSD might be a 5-HT1A
   or, more likely, 5-HT1C agonist -- although the role of the 5-HT2A receptor subtype is not at present well known.

Glennon-RA. "Do Classical Hallucinogens Act As 5-HT2 Agonists or Antagonists?" Neuropsychopharmacology. Vol 3(5-6):509-517. 1990.

   This is a rebuttal to Pierce and Peroutka's article in the same issue. It argues that LSD is a high-affinity, low-efficacy, nonselective 5-HT agonist, aka a dirty, partial agonist. Thus compared with
   high-efficacy agonists LSD would exhibit relative antagonist effects. Also, 5-HT1 sites have been shown to behave functionally as 5-HT2 antagonists, particularly 5-HT1A receptors. LSD's
   non-selective ("dirty") affinity for 5-HT receptors, and in particular 5-HT1A receptors, could explain other evidence which was offered in support of the 5-HT2 antagonist theory, and would
   explain certain biphasic dose/response curves that LSD has. The author does, however, conclude by noting that the 5-HT1C site may also (or alternatively) play a role in hallucinogenic activity,
   and that it should be explored.

