The indices of pharmacological range, risk coefficients, ED50, LD50, the size of the area of toxic activity, and maximal tolerated and absolute lethal doses were compared in hypodynamic mice. The pharmacological activity of the test neurotropic agents exhibiting a central action underwent change, but their toxicity remained unchanged

Kirichek, L. T.

English

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PHA 7OLpGICAL ACTIVITY AND TOXICITY OF SOME E
	 RQPIC .AGENTS
UNDER CONDITIONS OF M(PF01 F MI, I YPODYNAMIA
L. T. Kirichek
Translation of "Fanmakologicheskaya aktivnost' i toksichnost' nekotorykh
neyrotropnykh sredsty
 v usloviyakh eksperimental'noy gipodinamii",
Famakologiya i Toksikologiya, Vol. 42, No. 3, May-Jun 1979, pp 221-225.
01
(NASA-TM- 76371)
 PHARMACOLOGICA L ACTIVITY
AND TOXICITY OF SOME NEUROTROPIC AGENTS
UNDER CONDITIONS OF EXPERIMENTAL HYPODYNAMIA
(National Aeronautics and Space
Administration) 8 p HC A02/MF A01 CSCL 06T G5/52
N81-16724
Uncl as
14048
^QS G^^SS	
''.i
NATIONAL AERONAUTICS AMID SPACE ArIMINISTRATION
MSHINGION1 0 D. C. 20546	 SEPTEKBER 1980
STANDARD TITLE PAGE
1.	 Roper# No.
NASA U1-76371
2, Government Accession No, 1.	 Recipient's Catalog No.
d. Title and Sulrtille pjLAAjMAMtWjCAX1TMlVnyy AND S. Report Dote Septt'all} er 1980
MXICIV OF :"W N=R+ MPIC AGMM. UM HR COME- d. Performing Oroonwellon CodeTIONS OF BMIMIMML HYPODYNAMA
7.	 Author(s) 1.	 Performing Oroanisollon Report No.
L. T. Kiriclek
10. Work Unit No.
V.	 Parlormtno Otooniso ► en Nome and Address	 11.
l l,eo,Kanner Associates
Contract or Grant No.
X71. W-:1199
Redwood City, California, 99063	 13, Typo of Report and Period Co ve r ed
Translation
12.	 Sppnsoti o ♦looney Nome and Address'
Nationa	 Aeronautics and Space Administration
14,	 Sponsoring Agenc y CodeWashington, D. C. 20546
IS.	 Supplementary Notes
Translation of "FarmakologicheAcaya aktivnost' i toksicl=st' nekotorykh
neyrotropnykh srcdsty v usloviyakh eksperinlental t noy gipodinamii",
Farmakologiya i Toksikolog ya, Vol. 42, No. 3, May-Jun 1979, pp 221-225.
16.	 Abstract	 '
Comparison of M50 , the indices of pharmacological range, M 0,
risk coefficients, the size of the area of toxic activity,Rximal tol^ra-
ted and absolute lethal doses showed in acute experiments on intact and
"hypodynaiW c" noise that tinder conditions of a short term tension-producing
hypodynamia in the aninial,s, the pharmacological activity of the test neu-
rotropic agents exhibiting a central action n undeTgoes change wlyxe as the'
toxicity remi.ns unchanged.
i
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Unclassified Unclassified
D
PFMMAOOU)GICAL AC'rMTY ADD TU7am"i or SOME N URMWIC =2M
UNDER CONDITIONS OF FXPERIM WAL HYPQUXNAM
L. T.Kirichek
Pharmacology Deparmint (Head - Prof. N. S. Kharchenko),I` 
r kov Medical Institute
Most of the research done in respect to the effect of hypodynamia on sensi-
	 221*
tivity to drugs and poisons has been carried out under conditions where animals
were kept immobilized for a 1^-iV time (10-100 days) . The purpose of the present
work was to study the type and, degree of change in pharmacological activity and to-
xicity of preparations having a central neurotropi.c effect nt thvi early stages of
experimental hypodynamia.
Research Method
The experiments were carried out on 2 , 600 white mice of both sexes weighing
15-30 g. Hypodynamia was achieved with special, box cages that severely restricted
animal activity but did not make daily care difficult. The period of hypodynamia
was 24 hr at the end of which mouse stress reaction reached its maximal expression
(L, T. Kirichek, 1976). The substances studied were sodium oxibutyrate, barbamyl,
mazyl, reserpine, morphine, analgine, ethymizol, strychnine, eleuthexococcus, ephe
drive and melipramine. All preparations, with the exception of sodium oxi.butyrate
which was administered IF and reserpine which was administered internally, were giv-
en subcutaneously, once, in the form of aqueous solutions, reserpine in the form of
a suspension. in 1% stan,:h paste, in dosages evenly distributed from ineffective to
absolutely lethal. Pharmacological activity of the preparations was assessed by the
pharmacological effect proper to each (Table Z), observed visually or determined
instrumentally and toxicity was judged by the demise of the animals. On the basis
of the administration of a number of doses by the method of Litfield and Wilwxscn
(1949) each prel\aration was assessed for Mss and LD50' the index of pharmacologic- /224
al effective range (M. L. Belen'kiy, 1963), the risk coefficient at the level of
toxic dosage effect (I. P. Ulanova, 1970), the toxic activity zone and likewise re-
sistance and tolerance on the part of the animals to the effect of the medications
Numbers in the margin indicate pagination in the foreign text.
1
under study judged by the size of maximal tolerable and ahaolutely lethal doses
(V. D. Rozanova et al.,19i5). The control group canWised mice kept under conditions
of free behavior in the vivarium.
Results
Under oor4itions of experimental hypodynamia the type of effect of the neurc-
tropic agents studied did not change and their proper effects were clearly manifest-
ed both in thaws intact as well as in the "hypodynamic" inice although the degree of
pharmacological activity of the preparations underwent a reliabli change (see Table
I) Increase in t 10 pharnaoolog t"Al activity of preparations under hypodynamic con-
ditions ;vas regularly associated with an increase in the range of pharmacological ef-
fect and decrease in activity with decrease in range.
There was no substantial change in the toxicity of the neurotropic agents stud-
ied: under hypodynamic conditions (Table 11). Only the Lb 50 for ephedrine went down.
In,Iypndynainaa titre was likewise no change in the degree of risk for the prepara-
tions studied, including ephedrine, at the level of their activity in toxic doses.
judged by the criteria proposed by I. P. Ulanova (1970) the risk level was identical
in both sets of exlxriments. The "tolerance" of the animals was steadily maintained
when the preparations were administered: the figure for absolutely lethal doses for
most preparations was the same as in the control. Mouse "resistance" to the sub-
stances under study was mare labile under hypodyriamic conditions.
Thus, hypodynami.a, which induces in animals a condition of fear and stress,
changes organic sensitivity in respect to neurotropic drugs.
conclusions
1. Short term hypodynamia has no effect on the type of action exerted by cen-
tral neurotropic agents.
2. Under these conditions there is an increase in the pharmacological activity
of sodium oxibutyrate, amzyl, reserpine, morphine, analgine, strychnine, eleuthero-
coccus, ephedrine and melipramine, characterized by a drop in the ED 50 figure and an
increase in the range of pharmacological effect. In this context there is a drop in
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4
	
OF POOR QUALI'1TY
t
the pharmamlogical activity of barben,yl and ethymizol.
3. The toxicity of the preparations studied having a central neurotropic ef-
fect showed no change in an acute experiment with mice subjected to short term hypo-
dyTovia. as compared with the control.
5
Rte''' tlrN=.
1. Delen' kiy, M, L. , Elenr-nty kolichestvennoy otsenk-i r ttiako] ^irhoskogo effekta(dements of QW6 tat ve assessment of	 c+o og ca 	ect] , Leningrad ,
1963, pp 97-110.
2.. 1Cirichek, L. T., v kn. Is l'zovani a laboratorn kh zhivotn kh v razrabotke, Lro-
izvodstve i kontrole bio cheakikhis
	
a atov Use of labora-
tory Animals in the lets qm=t, Conducting mid Control of Blbniedical Prepara-
tions), Moscow, 1976 0
 pp 91-93.
3. Rozanova, V. b., G. Az Anton= and T. A. Bal'magiya, Pat. fiziol.., 6, 50-59
(1975).
a. Ulanova, T. P. v kn. 15rintsipy predel l no dopustinwkh kontsentratsi vradn kh
treshche5tv V voxdukhQ axo z stvenn ►
._h.. nes	 Y	 Principles o Thresh-
a	
r 
s i ib Concentrations  off' Harmful,ubstances in t)e Air of industrial.
Plants), Moscow, 1970, pp 65-75.
6


Pharmacological activity and toxicity of some neurotropic agents under conditions of experimental hypodynamia

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