SYNTHESIS: (from indole) To a well stirred solution of 10 g of
indole in 100 mL MTBE, cooled to 0 °C with an ice bath, there was
added 8.6 g oxalyl chloride. The reaction mixture was stirred for 0.5
hr, and the solids removed by filtration and washed twice with 50 mL
MTBE. This acid chloride was added to 20 mL anhydrous
diisopropylamine. There was then added an excess of 2N HCl, the
mixture cooled, and the resulting solids removed by filtration. These
were recrystallized from MeOH to give, after air drying, 11.4 g (49%)
indol-3-yl N,N-diisopropylglyoxylamide with a mp of 200-202 °C.
A solution of 11 g indol-3-yl N,N-diisopropylglyoxylamide in 350 mL
anhydrous dioxane was added, slowly, to 19 g LAH in 350 mL dioxane,
which was well stirred and held at reflux temperature under an inert
atmosphere. After the addition was complete, reflux was maintained for
an additional 16 h, the reaction mixture cooled, and the excess
hydride destroyed by the cautious addition of wet dioxane. The formed
solids were removed by filtration, washed with hot dioxane, the
filtrate and washings combined, dried over anhydrous MgSO4, and the
solvent removed under vacuum. The residue was dissolved in anhydrous
Et2O and saturated with anhydrous hydrogen chloride. There were formed
crystals which were recrystallized from benzene/methanol to give 4.5 g
(40%) of N,N-diisopropyltryptamine hydrochloride (DIPT) with a mp of
198-199 °C.
(from tryptamine) A solution of 1.60 g tryptamine base in 10 g melted
sulfolane was treated with 8.5 g isopropyl iodide and 6.5 g
diisopropylethyl amine, and held at steam bath temperature for 12 h
with occasional shaking to mix the two phases. This mixture was then
added to 100 mL H2O, and extracted with three 30 mL portions of
hexane. These were combined and, after removal of the solvent under
vacuum, the residue was distilled at the KugelRohr to give an
off-white oil boiling at 170-185 °C at 0.05 mm/Hg weighing 1.37 g
(56%) that spontaneously crystallized to a solid, mp 69-71 °C.
Recrystallization of a sample from hexane produced a white product
with a mp of 72-74 °C. IR (in cm-1): 742, 791, 1009, 1133, 1162,
1198. MS (in m/z): C7H16N+ 114 (100%); C4H10N+ 72 (38%);
indolemethylene+ 130 (18%); parent ion 244 (<1%). A solution of 0.50 g
of the free base in 2.5 mL isopropanol was treated with 0.5 mL
concentrated HCl and slowly diluted with Et2O with good
stirring. There was thus obtained, after filtering, washing and air
drying, the hydrochloride salt with a mp of 192-193 °C. The
infra-red spectrum of this salt was the same from either source; IR
(in cm-1): 752, 773, 935, 972, 1138, 1183.
DOSAGE : 25 - 100 mg, orally
DURATION : 6 - 8 hrs
QUALITATIVE COMMENTS : (with 18 mg, orally) "Wild effects noted
in an hour. Remarkable changes in sounds heard. My wife's voice is
basso, as if she had a cold -- my ears with slight pressure as if my
tubes were clogged but they aren't. Radio voices are all low, music
out of key. Piano sounds like a bar-room disaster. The telephone
ringing sounds partly underwater. In a couple more hours, music pretty
much normal again."
(with 25 mg, orally) "Within the first hour I noted changes already,
and my hand-writing became very poor. I cannot seem to measure the
rate of the drug's effects as there is no obvious window through which
I am moving. Abrupt sounds have golden spikes attached to them as
after-sounds, but I can't focus in on any other sensory changes. I
moved into a completely quiet environment and there don't appear to be
any effects of any kind. If I were deaf, this would have been an
inactive compound. How many other drugs have appeared to be inactive
because I didn't know where to look for effects?"
(with 50 mg, orally) "Everything was auditory, and I can only describe
it with a '!'"
(with 100 mg, orally) "Nothing until 35 minutes when a definite change
in hearing was observed. There was a decrease in high frequency acuity
with an unusual tonal shift of all frequencies to a lower
pitch. Voices sounded very similar to a single side-band radio signal
which had been mistuned to the low side of the center frequency. All
familiar sounds became foreign, including the chewing of food. No
effects were noted with respect to clarity of speech, and both
comprehension and interpretation were normal. Music was rendered
completely disharmonious although single tones sounded normal. There
were no changes in vision, taste, smell, appetite, vital signs, or
motor coordination. The effects began to fade at four hours post
ingestion, and were completely gone at eight hours. Mild diarrhea
occurred from five to ten hours post-ingestion but was not a
significant problem."
(with 250 mg, orally) "Shortly after I ingested the substance I heard
a spirit say, 'Once in a lifetime.' She encouraged me to believe that
I would have more life after the experience. But, there was a feeling
of foreboding. The light was there, but DIPT was the body of
Satan. The voices of people were extremely distorted -- males sounded
like frogs -- children sounded like they were talking through
synthesizers to imitate outer space people in science fiction
movies. In fact I felt that I was somehow sent into an anti-universe
where everything looked the same as normal but was a cold and empty
imitation. I felt I was a fallen angel."
(with 8 mg, smoked) "In four minutes I was aware of things going on,
and by eight minutes, I was at a plus 2. My tongue was numb, and my
ears felt plugged up although my hearing was keen and there was a
background hissing sound."
EXTENSIONS AND COMMENTARY: Most psychedelic drugs affect,
primarily, the visual sense, but here is one that shows its effects
primarily in the auditory system. And it screws it up in a most
unlinear manner, in that there in not just a simple decrease in pitch
which would be as if someone had his thumb against the LP record and
made everything come out at a 3/4 speed text, or a 1/2 speed
text. Actual roportionality is lost, so there is complete harmonic
distortion.
A physician friend of mine has expressed it using a neurological
vocabulary: "If it [the drug] delayed only the neural response to a
stimulus, then pitch might have been shifted down, and yet harmony
between notes should have been preserved. A variable delay related to
the pitch of the stimulus would produce the disharmony but would not
explain the preservation of normal relationship between single
tones. It seems clear that this compound affects the auditory
processing centers in the brain in a complex way which deserves
further scientific study. The lack of significant toxic effects should
make this compound useful for further studies."
I am in absolute agreement. Here is a drug that goes directly after
the hearing system, rather than the seeing system. Let's stick a
carbon 11 on one of those isopropyl groups, and see where the drug
goes using the positron emission tomography camera. Will we highlight
the auditory cortex? Or maybe some association area? But if we are
indeed dealing only with musical pitch, not musical structure, there
might be only a small part of that cortical region visible. This could
well be a tool for two things. First, the localization of the pitch
center in the brain. And second, it is a prototypic drug that might
allow structural modification in several directions with several
augmenting atoms. Some simple homologue might well have even more
remarkable and specific properties. If you don't look, you won't
find.
I have been told by an adventurous graduate student that a study has
been made with two subjects who had absolute pitch, employing a piano
and a sine-wave generator as a sound source. He wanted to explore the
possibility that some relationship could be developed between the
pitch of the note provided and the apparent pitch of the note
perceived. No meaningful relationship was found, except for the
reinforcement that the observed drop in pitch was not linear, in that
true distortion rather than simple pitch dropping was always
observed. Most interesting was the plot of the error for each note
against the elapsed time. This provided what could be seen as an
almost-quantitative measurement of the drug's intensity and
chronology. Pretreatment with relatively small amounts of MDMA (35
milligrams, at between 1.5 and 2.5 hours before DIPT, at 55
milligrams) led to an exaggerated distortion, with an enhanced
intensity that verged on being painful.
The homologue with only one isopropyl group on the nitrogen,
N-isopropyltryptamine or IPT, has been made according to the same
recipe, with the indol-3-yl N-isopropylglyoxalylamide (mp 199-200
°C from methanol) obtained in a 98% yield, and the amine
hydrochloride (mp 245-246 °C from benzene/methanol) obtained in a
60% yield. The free base distilled at 130-140 °C at 0.1 mm/Hg to
give a fraction that spontaneously crystallized to a very hard
solid. MS (in m/z): C4H10N+ 72 (100%); indolemethylene+ 131 (60%), 130
(32%); parent ion 202 (3%). No active level has yet been found in man,
to my knowledge.
