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#91 IM
ISOMESCALINE; 2,3,4-TRIMETHOXYPHENETHYLAMINE
SYNTHESIS: A
solution of 8.0 g
2,3,4-trimethoxybenzaldehyde in 125 mL
nitromethane containing 1.4 g
anhydrous ammonium acetate was held at
reflux for 1.5 h. The conversion of the
aldehyde to the
nitrostyrene
was optimum at this time, with a minimum development of a slow-moving
spot as seen by thin layer
chromatography on
silica gel plates using
CHCl3 as a developing
solvent; the Rf of the
aldehyde was 0.31 and the
Rf of the
nitrostyrene was 0.61. The excess
nitromethane was removed
under vacuum, and the residue was
dissolved in 20 mL hot MeOH. On
cooling, the yellow
crystals that formed were removed by filtration,
washed with cold MeOH and air dried yielding 4.7 g yellow
crystals of
2,3,4-trimethoxy-beta-nitrostyrene, with a mp of 73-74 °C. From the
mother liquors, a second crop of 1.2 g was obtained.
A
solution of 4.0 g LAH in 80 mL THF under He was cooled to 0 °C and
vigorously stirred. There was added, dropwise, 2.7 mL of 100% H2SO4,
followed by a
solution of 4.7 g
2,3,4-trimethoxy-beta-nitrostyrene in 40
mL
anhydrous THF. The mixture was stirred at 0 °C for 1 h, at room
tem
perature for 1 h, and then brought briefly to a reflux on the steam
bath. After cooling again, the excess
hydride was destroyed with 4.7
mL H2O in THF, followed by the addition of 18.8 mL 15%
NaOH which was
sufficient to convert the solids to a white and granular form. These
were removed by filtration, the filter cake washed with THF, the
mother liquor and filtrates combined, and the
solvent removed under
vacuum. The residue was added to dilute H2SO4, and washed with 2x75
mL
CH2Cl2. The aqueous
phase was made basic with 25%
NaOH, and
extracted with 2x50 mL
CH2Cl2. The
solvent was removed from these
pooled extracts and the amber-colored residue
distilled at 95-100 °C
at 0.3 mm/
Hg to provide 2.8 g of
2,3,4-trimethoxyphenethylamine as a
white oil. This was
dissolved in 20 mL IPA, neutralized with about 1
mL concentrated HCl, and diluted with 60 mL
anhydrous Et2O. After
filtering,
Et2O-washing, and air drying, there was obtained 3.2 g of
2,3,4-trimethoxyphenethylamine hydrochloride (IM) as a white
crystalline product.
DOSAGE: greater than 400 mg.
DURATION: unknown.
QUALITATIVE COMMENTS: (with 300 mg) No effects whatsoever.
(with 400 mg) Maybe a slight tingle at the hour-and-a-half point.
Maybe not. Certainly nothing an hour later. Put this down as being
without action.
EXTENSIONS AND COMMENTARY: Some fifty years ago this material was
given the name "reciprocal mescaline" in that it was believed to
exacerbate the clinical symptoms in
schizophrenic patients. In the
original report, one finds: RThus we have discovered an extremely
remarkable dependency of the intoxicating action upon the position of
the three methoxy groups.
Mescaline, the
3,4,5-trimethoxy-beta-phenethylamine, produces in the normal subject a
much stronger over-all intoxication than in the
schizophrenic patient,
whereas
2,3,4-trimethoxy-beta-phenethylamine has quite the opposite
effect. It has little action in healthy individuals, being almost
without intoxicating properties, but it is very potent in the
schizophrenic. The
metabolic conversion products of the "reciprocal"
mescaline will be further studied as soon as the study of the
metabolism of the proper mescaline is complete.
This is a pretty rich offering, and one that the present medical
community has no qualms about discarding. At the bookkeeping level,
the promised further studies have never appeared, so all may be
forgotten as far as potential new discoveries might be concerned.
One recent related study has been reported, tying tog
ether
isomescaline and schizophrenia. Through the use of
radioactive
labelling, the extent of
demethylation (the
metabolic removal of the
methyl groups from the
methoxyls) was determined in both
schizophrenic
patients and normal subjects. When there was a loading of the person
with
methionine (an amino acid that is the principal source of the
body's
methyl groups), the
schizophrenics appeared to show a lesser
amount of
demethylation.
But might either of these two observations lead to a diagnostic test
for schizophrenia? At the present time, the conventional thinking is
that this probably cannot be. The illness has such social and genetic
contri
butions, that no simple measure of a response to an
almost-
psychedelic, or minor shift of some urinary
metabolite pattern
could possibly be believed. No independent confirmation of these
properties has been reported. But maybe these findings are valid. A
major problem in following these leads does not involve any complex
research protocols. What must be addressed are the present regulatory
restrictions and the
Federal law structure. And these are formidable
obstacles.
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