(SANITIZED)UNCLASSIFIED CZECH PAPER ON THERAPEUTIC TRIALS OF NEW PHENOHARMANE PREPARATION(SANITIZED)

• Document Type: CREST
• Collection: General CIA Records
• Document Number (FOIA) /ESDN (CREST): CIA-RDP80T00246A016500120001-5
• Release Decision: RIPPUB
• Original Classification: C
• Document Page Count: 8
• Document Creation Date: December 22, 2016
• Document Release Date: December 13, 2011
• Sequence Number: 1
• Publication Date: May 16, 1962
• Content Type: REPORT

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Summary from the report of the Psychiatric Department of the
University of J.E.Purkynje, Brno. Director: porf.MUDr.J.Hgdlik
Therapeutic trials of the new czechoslovak preparation Phenoharmane
K. Ndhunek, A.Rod ovd, J.Bo j enovskk
Phenoharmane was administered at the psychiatric department
in Brno to a total number of 35 psychotic subjects /28 women,
7 men/. The age of the patients varied from 15 to 68 years. In
spite of the diagnostic inhomogeneity of the treated group there
was a uniform trend in all cases with minor exceptions only.
They all represented an acute course of the first attack of the
illness or an execs baton of the periodically recurring psycho-
sis with a prevalently good prognosis.
Phenoharmane was administered at daily doses of 250-1500 mg
orb, In cases of manic syndromes intramuscular injections at
maximum doses of 150 mg were used at the same time. In manic syn-
dromes daily doses of the drug fluctuated about 1 gr daily, often
they were even higher. In one case of schizophrenia the treatment
was combined. with pentazol convulsions. The duration of the treat-
ment was 6-33 days. Before and during the treatment the GOT,GPT
abd alcaline phoaphatase in serum were controlled together with
the leukogram? routine urine investigation, sedimentation rate
etc. at regular intervals. Therapeutic results are sumnarized in
table No. 1.
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Tab.No 1.
Diagnosis
therapeutic results c~lssified according
to the Serej`sky method
A-B
C
D,
0 -
total
Schizophrenia
4
3
1
7 1
16
Paraphrenia
1
-
2
1 -
14
Manic syndromes
1
1
-
4 5
11
Deranged behaviour
2
1
-
- -
3
Huntigton 's chorea
-
1
-
- -
1
Total
8
6
3
12 6
35
%
22,8
17,1
8,7
34,3 17,1
At the first glance the table shows the relatively low
therapeutic, value of the drug. The transient ddephorizing effect
of the drug was observed in 3--from 11 sub, a cta;r. Very interesting
was the favourable effect in some derangements of behaviour in
adolescent subjects which was nevertheless in. one case controlled
also by placebo. All three cases showed dissociability effects
as mendacity, lose of discipline, angry and refractory reactions,
representing allways educational problemte. The number of such
cases is however toosmall to allow definite conclusions. A dou-
ble blind test is needed to meet the problem of the effectiveness
of the drug in similar cases. In one case of Huntington'. chorea
Phenoharmane caused a reduction of hyperkinesia and tremor to
approximately the same degree as successive administration of
reserpine. More trials-in some other hyperkinesias as in chorea
minor are suggested.
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Side-effects observed during the treatment with Phenoharmane
were toxic morbilliform eruptions in one case, uncharacteriatict.L
headaches in two 'cases. The extrapyramidal symptomatology known
to occur during the treatment with reserpinewas not observed.
Values of GOT,GPT,alcaline phosp~tase, Takata turbidity reaction,
and leukogram were essentially normal. In one case of schizophre-
nic women in which the treatment with Phenoharmane was combined
with convulsions a prolonged apnoic pause with a collapse of short
duration was provoked by the pentazol convulsion. The patient
recovered spontaneously. This case recalled of the previously
described complications of the combined reserpine and electro-
shock therapy. It is therefore recomendable to bear in mind this
danger and not to combine Phenoharmane with the convulsion the-
rapy.
All subjects which showed an insufficient effect after the
Phenohaxmane administration were treated with other drugs as
chlorpromazine, reserpine or in several oases with thioridazine
and perphenazine. From 24 subjects this therapy caused full recove-
ry in 18 /type of remission A-B/,partially recovered 4 /type C/
and unchanged remained 2.
If the experiments with the immediate results of the Pheno-
harmane treatment are summarized in an intraindividual compari-
son with currently used neuroleptics,' so Phenoharmane presents
itself as a relatively less effective and less suitable drug
for the monotherapy of psychotic cases. The do pphori zing effect
of the drug could be-with difficulties.only employed in this the-
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rapy of manic syndromes owing to its insufficient influence
on the psychomotor component which makes a more effective
therapy necessary in a short time. Further therapeutic trials
are suggested in the above mentioned cases of deranged behavi-
our in adolescents and in some extrapyramidal hyperkinesias,
e.g. chorea minor. Some consideration deserves also the previ-
ously demonstrated interference of Phenoharm ne with the metabo-
lism of serotonin which could possible be employed in some
combined treatments with monoaminooxidase inhibitors, such
trials being now in progress at this clinic.
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References to Phenoharmane
11 Protiva M.et al.,Synthetic models of hypotensive alcaloids.
I.1-aralkyl-1,2,3-tetrahydronorharmane group.Chem.
Listy 51,1915,1957 /in.czech/.
2/ Trdka V.,Van6dek M.,Hypotensive effects of 1-substituted
1,2,3,4-tetrahydronorharmanes.Chemotherapeutics and
their evaluation. Summaries of papers read at the
Pharmaceutical Symposium,; Praha 3-7.9.1956.Edited by the
Pharmaceutical Section of the Cz.Med.Soc.of J.E.Purkyn,je, ;
p.72 /in.,czech/.
3/ Vinaf O.,New trends in the psychiatric pharmacotherapy.Read
at the R.gional Psychiatric Seminar in Brno,24.5.1958.
Farmakoterapeutickd zprdvy OIS,4,171,1958 An czech/.
4/ Vine O.,New psychotropic drugs.R ad at the Psychiatric Semi-
nar in Ldzn6 Jesenik, 9.1,199. /in,,,Uz~ a h/.
5/ D1abat A.,Macek K.,Vand ek M.,Trdka V.,Reserpine-like effect
of Phenoharmane.0s.Fysiol.,8,177,1959 /iceh)
6/ Hord kovd E., Vojt6chovsky M.,Experiences with-the Clyde *s
method designed to reflect the changes of emocionality
under the influence of tranquillizers and psychostimu-
len is .Read at the Psychiatric Seminar in Ldzn6 Jesenik,
7,1,1960 An czech/.
1/ Dlabad A.,The effect of Phenoharmane and cyanacethydrazide
from the standpoint of 5-hydroxytryptamine and inhi-
bition of aminooxydase. Dissertation 1960, VUFB An czeehi
A/ Vinai' 0.,Phenoharmene in psychiatry.Preliminary report. Die- STAT
cussion at the Internat.Congr.of Psychiatry in Basel,
10.7.1960.
9/ Vinaa O.,The use of a new czech.preparation Phenoharmane in
psychiatry.Cas.Ldk.des.,99,l422,1960 /inch/.
10/Vitek Vl.,Vojtechova]c M.,RyIS nek K. Kuhn E. Comparison of
the effects of Phenoharmane and reserpine on the meta-
bolism of serotonine, tryptamine, energy metabolism and
central nervous activity. Activ.Nerv.Sup.,2,360,1960
11/Ndhunek K.,Rodovd A.,tojenovel J.,Therv~ppeutic trials with a.
new cz.preparation Phenoharmane. Cal.psyehiatrie,1961.
-in print /inch/.
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~h~a-oharmane, a new dyaphoria producing drug
O1dich, V i n a
/Institute for F'obtgrr-aduate medloai Education, ?rogue ./
.1Ttenohr:rm- ae. ii 'brand of bb 3)azyl.~etrc,.hydronorharm,~:ne,
xcp ? sc:l;:ir; c 4 ap . i,xied model of ?e erpine. It was ynthetised
,z VROA, i t R
b Pro- V
y 1eco 0 ~,,1c,' 1 dal. opertJ r_,:; were investigated
by T:Zle-so..4,nd coil. The epnmpotu?"d PoL3Gcm-tea 3xi lower doges comb
sffect s of r eF3erpino charactew /enhL.ncoe ' excrota.or: of 5-1IIA.i and'
potOnciateo Thiopentale anc,eathc:ala x1 L:?ice, cou4es a ptosis, fall
of temperature eta./r in higher-dos-es chovwee convulsive effectp.
Clinleca, trials were Curare on 32 ;ub jeats, including
19 ruuriiode re.~siVO
A FSych?sca' in the mfxaio phttse, ]. mnnio syndromo
in progreosive. paralysio, 10 cci iw. ophreni.ce and 2 psychomotor
excitL-tions.in ,p ,y*ehogenio Icyaho.ses. Control studios with placebo
designed as double blind test *rwcre not undertaken. -5 subjects
were thoir ovdn control, when rb7.Epse folowed the interruption
of the treotement.. The. doses qf..' OQ - 90Q mg were administered c .9
daily for a period from 10 days to 2 months. 'Pheiioharmana Is
practically a nontoxic drug,- end no particular side effects -were
observed during its 'administration,..
Best result a were found In any
~. ~.ic canditians.F rom 19 treated
g~ab1ects a complete cure we attuned jn '1:2. In 8 of then subjects
i r.
the cure is e.--specially clui.ck, being effected in a period of: 10 days.,
In other 2 eub,jecte favour~Eible Influenoe' was also observed e3 eoiall-..;
emo
onal 'c
in
,.
. _--_
omPonen s of the diseases the elation disappeared,
nevertheless the psychomotor ex-citation was only insignificantly Instead of the euphoria a moroai,ty and raisonning was
observed. One ease of manic sy-ndromy in progressive p x_.lysIs
/general p? alysis/ showFrec disap aeczra.n.ce of euFb.oric; stctes t.h
the hyperactivity was inhibited only partially. In 5 idcsea of 10 sehi
zo hT.1orlas Phenoharnane was eora,p1otely without effect and in another
5 Oaeoa the effect-wag not 'v'ery pronounced, causing, , on1jy. acme. shift
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Phenoharmsne Pig 2'4
in the synttomatology in the direction . of the depression.
'As primary indication of Phenoharme ne figures the m6nio
vihioh dissociates urider' its influence in its enhanced
ndrome
s
, ,
y
psychomotor' ao uivity and the proper affective oomponente. Pbenohar-
mans afteets selectively the wood, whereas the psychomotor component
influenced.' It 3 dbsorved espa oially after
;f
t1
an
,
.y
is On-Ly J.nsit c
the i.v. adminis3trationt when a glad and happy person ohanges during
the injection in a very unhappy, depressed and anxious one, beginniq,-
even to weep. This state is in contrast with the preserved exoited
mimics and behaviour.
Inasmuch as Imipramine is called a thymoleptio drug, then
Phenohsrmane could be designed as a' dysphorio drug... Both drugs are?
selectively affecting the emotions and act as mutual. antagonists.
Zvea if 3n .the future the Phenohurmane with not aPPerr'olinioallY
usefull, neveithellee its '-effects are -interesting enough-from the
etuadpoint; of theoreotioal investigation.
xl
%'
Research tnetitute for ? Pharmaoyr and Biochemistry, Prag3te
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