Study of 65 cases

Ethyltryptamine acetate is an effective psychic energizer for patients with reactive depression but has little effect on the rigidity and tremor at Parkinson's syndrome or paralysis agitans. Side effects are minimal and transient.

A potent, reversible inhibitor of monamine oxidase has recently been synthesized.( n1) This drug, ethyhryptamine acetate (Monase), is apparently devoid of toxicity. It has the interesting pharmacologic property of inhibiting the enzymatic destruction but not the production of serotonin.( n2) Because of this specific property, it was thought that ethyltryptamine acetate might be of clinical value as a euphoriant in the therapy of patients with Parkinson's syndrome, paralysis agitans, and reactive depression.

The chemical structure of ethyltryptamine acetate is shown below.

DIAGRAM
Materials and methods

For this study, 56 patients selected from the wards at Oak Forest Hospital were divided into 4 groups. Group A was composed of 10 patients with Parkinson's syndrome and 8 with paralysis agitans. The ages ranged from 38 to 74 years, with a mean of 61.2. Group B consisted of 27 patients with a clinical diagnosis of reactive depression, and the ages ranged from .13 to 66 years, with a mean of 52.1. These patients were started on 10 mg. of ethyltryptamine acutate twice daily; the dose was increased to 15 mg. three times daily in the last two weeks of therapy. Duration of treatment varied from five to seven weeks.

Group C, 8 patients with a mean age of 68.5 years, was a counterpart of Group A and served as a placebo control group, while group D, 3 patients with a mean age of 56.3, was the placebo-treated control for group B.

A complete blood count, urinalyses, and a nonprotein nitrogen determination were done on each patient before and after the study. Blood pressure readings were recorded biweekly.

A number of patients were chosen at random and were evaluated psychometrically with the S.R.A. Non-Verbal( n3) and the Thurston Temperament tests( n4) before and immediately after therapy. The patients were interviewed weekly, and subjective response and/or side effects were recorded.
Psychometric observations

Ethyltryptamine acetate appears to be an effective psychic energizer. With few exceptions, the 7 personality traits evaluated showed that the patients receiving therapy exhibited a better adjusted and better balanced emotional pattern and a more realistic approach. Average results of the personality tests which were conducted before the beginning of the study and after the administration of ethyltryptamine and the placebo are shown in figure I. It is noted that there is a definite tendency for the personality traits to be closer to the midline (50 percentile) after the administration of the drug. This indicates that the patients' general personalities improved during ethyltryptamine therapy. Patients were less withdrawn or passive and were more socially responsive. Greater confidence in ability and improvement in personal attitude and care were observed. Generally, the patients were more at ease, more serf-reliant, and better integrated. No significant change was noted in the placebo groups.

Tables 1 and 2 demonstrate the changes in the drug and placebo groups as determined by the psychometric tests.( n3, n4) There was an increase in mental reactive time from an average percentile of 5.40 to 7.25 after medication with ethyltryptamine--a gain of 1.85, which is significant for this age group. The placebo groups, by contrast, showed an insignificant change of 0.18. In temperament analysis, the results were parallel-an average percentile increase of 5 in the drug-treated groups, compared with a decrease of 1 in the placebo groups. The psychometric studies are summarized in table 3.
Other observations

In approximately one-third of the patients receiving ethyltryptamine therapy, drowsiness and minor tremulousness appeared during the first ten days of treatment. These symptoms were of minimal degree and transient, disappearing as therapy continued.

There were no significant changes in blood morphology, urinalyses, or blood chemistry during and immediately after therapy with the drug. No effect on blood pressure was noted.
Discussion

It has been postulated that the monamine oxidase inhibitors act by blocking the enzymatic destruction of serotonin anti catecholamines, thus increasing the brain levels of these substances.( n5) Ethyltryptamine appears to have an advantage over other monoamine oxidase inhibitors in its specific effect of inhibiting the enzyme which destroys serotonin without acting on the system that produces the agent.( n2) The result, therefore, would be a higher serotonin concentration in the brain than that achieved with other related monamine oxidase inhibitors.

Indeed, our results indicate that ethyltryptamine is an effective psychic energizer. Tables 1 and 2 illustrate the improvement in our patients with parkinsonism, paralysis agitans, or reactive depression of varied etiology. Table 3 summarizes our study. We believe that the psychometric testing employed( n3, n4) is an objective approach in psychopharmacodynamics, extended with weekly interviews and observations.

While receiving ethyltryptamine, our patients were less lethargic, tense, confused, and depressed; exhibited a greater interest in their personal appearance; and were more amenable to psychotherapy.

In variance with the reported benefit of ethyltryptamine acetate in parkinsonian tremor,( n6) we did not note any difference in tremor activity in our patients. In accord with reported findings,( n7, n the drug appeared to be of value in the treatment of patients with reactive depression in Parkinson's syndrome and in a geriatric population.
Secondary study

In order to fully conclude our opinion with reference to ethyltryptamine and its clinical effect on parkinsonism, we inaugurated an additional thirty-day study, choosing at random a group of 9 patients. This was effected because, during our initial study with the drug, Muether and associates( n6) reported specific conclusions in the treatment of Parkinson's disease that did not in any way seem compatible with our own findings.

Of the group of patients selected,( n3) had paralysis agitans; 3, postencephalitic parkinsonism; and 3, arteriosclerotic parkinsonism; all had severe rigidity and tremors. Trihexyphenidyl (Artane) and atropine-like drugs were discontinued. After several days without medication, ethyltryptamine was administered three times daily in 15-mg. tablets. Muether and associates( n6) used a combined daily dosage of 50 mg.

Results. After the third day on drug therapy, 2 patients had to be removed from the study because of a marked increase in tremors and rigidity; their former medication was restored. Approximately no change in neurologic examination was manifested by 2 patients, although, in 1 of the patients, anxiety was relieved and headache was lessened, and the patient was more cheerful. The remaining 5 patients continued the ethyltryptamine regimen for the remaining period of the study, in spite of the deterioration of their condition. In several of the group in whom there was a marked increase of tremors and rigidity, an increased state of disorientation was definitely noted (table 4).

The ethyltrytamine acetate used in this study was provided as Monase by the as Monase by the Upjohn Company.
Table 1 Psychometric evaluations before and after ethyltryptamine acetate therapy

Legend for Chart:

A - No.
B - Patient
C - Age
D - Date drug therapy began (1961)
E - Date drug therapy ended (1961)
F - Rating before drug therapy (percentile) Mental reactive time
G - Rating before drug therapy (percentile) Temperament
H - Rating after drug therapy (percentile) Mental reactive time
I - Rating after drug therapy (percentile) Temperament
J - Clinical response

A B C D E F
G H I J

1 F.R. 54 April 6 May 13 0.25
22.5 1.25 43.5 Excellent

2(*) R.S. 50 March 22 May 13 0.02
40.5 0.03 39.5 Questionable

3(*) E.W. 55 April 4 May 13 0.75
29.0 2.0 41.5 Excellent

4(*) D.C. 74 April 7 May 9 0.35
26.5 0.75 28.5 Questionable

5(*) B.V. 67 April 7 May 9 0.35
29.5 0.75 29.5 Questionable

6 V.S. 52 April 6 May 13 1.00
36.5 2.5 41.0 Excellent

7 J.F. 43 April 6 May 13 0.25
35.0 0.75 39.5 Good

8 H.F. 63 March 24 May 13 0.25
33.5 0.45 42.5 Good

9(*) M.C. 38 April 6 May 13 43.0
43.5 48.0 43.5 Good

10(*) D.B. 58 April 4 May 13 6.0
37.0 11.0 44.5 Excellent

11 F.B. 66 April 6 May 9 0.50
33.5 2.5 41.5 Excellent

12(*) E.N. 64 April 6 May 13 1.25
39.5 1.75 43.5 Good

13(*) H.B. 70 April 4 May 13 8.00
39.5 10.5 42.5 Good

14 B.G. 43 March 23 May 13 1.0
37.5 1.50 41.5 Excellent

15 R.J. 44 April 6 May 13 0.50
38.5 0.75 39.0 Questionable

16(*) J.K. 66 March 22 May 13 0.25
390 0.75 42.5 Good

17(*) E.N. 70 March 24 May 13 28.0
38.5 38.0 40.5 Excellent

Average 57.47 5.40
35.26 7.25 40.26
(+1.85) (+5)

(*) Patients with Parkinson's syndrome

Table 2 Psychometric evaluations before and after placebo administration

Legend for Chart:

A - No.
B - Patient
C - Age
D - Date placebo therapy began (1961)
E - Date placebo therapy ended (1961)
F - Rating before placebo administration (percentile) Mental
reactive time
G - Rating before placebo administration (percentile) Temperament
H - Rating after placebo administration (percentile) Mental
reactive time
I - Rating after placebo administration (percentile) Temperament
J - Clinical response

A B C D E F
G H I J

1 V.B. 64 April 4 May 13 0.06
24.5 0.055 23.5 None

2(*) H.K. 72 April 7 May 9 0.25
27.5 0.35 28.5 Questionable

3 M.C. 53 April 6 May 9 0.35
28.5 0.15 235 None

4 M.U. 52 April 6 May 4 0.40
39.5 0.40 38.0 None

5(*) M.K. 72 April 6 May 13 0.25
41.5 0.35 39.5 Questionable

6(*) H.S 76 March 24 April 28 35.0
41.5 37.0 40.5 Questionable

7(*) B.W. 56 March 24 April 28 0.35
28.5 0.35 27.5 None

8(*) M.M. 54 March 22 April 28 1.00
44.5 1.25 44.5 None

9(*) A.N. 75 April 4 May 13 0.15
25.5 0.15 22.5 None

10(*) E.F. 74 March 22 April 28 3.00
36.5 3.0 39.5 Questionable

11(*) E.W. 69 March 23 May 13 0.75
40.0 0.50 39.5 None

Average 65.18 3 78
34.36 3.96 33.36
(+0.1 (-1)

(*) Patients with Parkinson's syndrome

Table 3 Response to psychometric testings of patients receiving ethyltryptamine

Legend for Chart:

A - Results
B - Drug group No. patients
C - Drug group Per cent
D - Placebo group No. patients
E - Placebo group Per cent

A B C D E

Excellent 7 41.18 0 0.00

Good 6 35.29 0 0.00

Questionable 4 23.53 4 36.36

Negative 0 0.00 7 63.64

Totals 17 100.00 11 100.00

Table 4. Response of 9 patients with parkinsonism to ethyltryptamine acetate

Legend for Chart:

A - No.
B - Patient
C - Age
D - Type of parkinsonism
E - Days an drug therapy
F - Response

A B C D E F

1 E.N. 64 Paralysis agitans 21 Poor

2 H.R. 60 Paralysis agitans 3 Poor

3 R.S. 50 Paralysis agitans 21 Poor

4 S.L. 66 Arteriosclerotic 21 No change

5 H.B. 70 Arteriosclerotic 21 Poor

6 E.F. 74 Arteriosclerotic 21 Poor

7 S.E. 55 Postencephalitic 21 No change

8 M.C. 38 Postencephalitic 3 Poor

9 M.M. 54 Postencephalitic 21 Poor

DIAGRAM: Fig. I. Comparative results of personality test given to 17 patients receiving ethyltryptamine acetate and 11 receiving a placebo. Solid line represents scores before study; broken line, scores after administration of placebo; and dotted line, scores after administration of ethyltryptamine acetate.
REFERENCES

(n1.) HEINZELMAN, R. V., and others: Synthesis of α-methyl-tryptophane and α and a alkyltryptamines. J. Organic Chem. 25: 1548, 1960.

(n2.) GREIG, M., E., R. A. WALK, and A. J. GIBBONS: Effect of three tryptamine derivatives on serotonin metabolism in vitro and in vivo. J. Pharmacol. & Exper. Therap. 127: 110, 1959.

(n3.) MAIER, N.R.: Psychology in Industry. Boston: Houghton Mifflin Co., 1946.

(n4.) THURSTON, L. L.: Dimensions of temperament. Psychometrica 16: 11, 1951.

(n5.) SHORE, P. A., and others: On physiologic significance of monamine oxidase in brain. Science 126: 1063. 1957.

(n6.) MUETHER, R. O., and others: Monoamine oxidase inhibitor in treatment of organic disease. J. Neuropsychiat. 2 (supp. 1): 80, 1961.

(n7.) TURNER, W. J., and s. MERLIS: Clinical studies with ethyltyptamine. J. Neuropsychiat. 2 (supp. 1): 73, 1961.

(n8.) KAST, E. C,: Alpha-ethyltryptamine acetate in treatment of depression; study of methodology of drug evaluation. J. Neuropsychiat. 2 (supp. 1): 114. 1961.

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By Eugene J. Chesrow, M.D., Medical superintendent and director, Department of Clinical Investigation; Joseph P. Musci, M.D., Director of clinical research, Department of Medicare Oak Forest Hospital, Oak Forest, Illinois; Sherman E. Kaplitz, M.D., Attending neuropsychiatrist, Department of Medicare Oak Forest Hospital, Oak Forest, Illinois; Raoul Sabatini, PH.D., Clinical psychologist, Department of Medicare Oak Forest Hospital, Oak Forest, Illinois and Jacob M. Levine, M.D., Attending clinician, Department of Medicare Oak Forest Hospital, Oak Forest, Illinois