Amitriptyline, but not chlordiazepoxide, protects rats from the occurrence of gastric erosions and ulcers following immobilization. When, however, chlordiazepoxide is given together with amitriptyline the protective effect of the latter is markedly increased

Blum, J. E.

Huerlimann, A.

English

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NASA TWO11CAL M HDRAN=
	 NASA TM-76197
EMET (W MCHMMIC DR= ON GASTRIC ULCM IIMUCED BY IM MIZATION.
INCREASED PICITWTIM EF='HET OF AMITRIPTYLINE CAUSED BY C LOMIAZEPDXIM
J. E. Blum and A. HuerliMWM
(NASA—TM-76197) EFVICT Of PSYCHOTROPIC
	
N60--27991
DRUGS ON GASTRIC ULCERS IN D UCED
IMMOBILIZATION: INCREAS.EDPfiC'IECTIVE EFFECT
OF AMITRIPTYLINE CATS
	
#PFll BY CEiLOtcDIAZEPDXTDF
	 Unc,las
(National Aeronautics dnd Space
	 ^ G3/51 26030
Translation of "Zur Bminflussung der durch Im obilisation ausgeloesten
Magenulcera durch Psychophanwka: Verr;taerkung der Schutzwirkung von
Amitriptylin Burch Chlordiazepoxid," Medicina et Pharmcologia En2gEimntalis,
Vol. 15$ No. 6 1 1966, pp 615-617.
NATIONAL AERONAUTICS AND SPACE ADMISTRATION
WASHINGrM, D. C.	 JUNE 1980
tSTANDARD tilt F PAGE
1.	 Room-t Pt,, h 	 Ooyernment Accession No
r^ ^^^^ pp
..p ion
^	 Recipient s Catalog No.
4.
	 Title and Subs=.tls
ral! CT OF PSYCHOTRUPIC DRUGS ON GASTRIC ULCERS
5.	 Re port Dote
JUNE 1980
6.	 Performing Orponisation CodeBY IMMOBILIZATION...
7.	 Authors)	
,,...._^,,...,.._.....,......	 .......,.........,_._.._^,..
J. E. Blue and A. Huerlimann
8.	 Performing Organisation Rnpor ► !fa,
10,	 Work Unit No,	 i
11.	 Contract or Grant No.
NAaw-31999.	 Performing Orgc ii:ation Name and Address
Leo Kanner Associates
Redwood City, California 94063 13, Type of Repoli and P eriod CoveredTranslation
12,	 Sponsoring Agency Nomi and Address
National Aeronautics and Space Administration
Washington, D. C. 20546 U. Sponsoring Agency Cnde
15,	 Supplementary Notes
Translation of 112ur Beeinflussung der durch Immbilisation_ausgeloesten
Magenulcera durch Psychopharmaka: 	 Verstaerkung der Schutzwirkung von
Amitriptylin durch Chlordiazepoxid," Medicina et Pharmaool 	 is	 rimer
talis, Vol. 15, No. 6, 1966, pp 615-617.
16.	 Abstract
Ami.triptyline, but not chlordiazepoxide, protects rats from the occur-
rence of gastric erosions and ulcers following immobilization. 	 When,
however, chlordiazepoxide is given together with ami.triptyline the
protective effect of the latter is markedly increased.
17,	 Key Words (Selected by Author(s)) 18.	 Distribution Statement
Unclassified-Unlimited
19.	 Security Ciossif. (of this report) 20.	 Security Clossif, (of This page) 21. No, ;-f Pages
	 22,	 Price
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r
NASA•1iQ
'.aFF7Cr OF PSYCHOT AOPIC MM ON GASTRIC UI CSRS INDiICED BY IMMOBILIZATION.
INC MSED PFC11ECTIVE EFX,T OF AMIITRI14 YLIM CAUSED BY MORDIAZEmaDE
J. E. Blum and A. Huerlimann
F. Hoffmann-La Roche & Oo., Basel, Switzerland
Several hours of immobilization produce erosion and ulceration in the rat	 615*
stomach (1j, 2). They are probably the consequence of a "stress reaction" (Selye)
which is also probably responsible in humtians for ulcers that occur following psychic
trauma, burns and infection,, ;. In this context corticoid treatment prorates the oc-
currence of erosion (3).
The assuatption of a central origin for erosions following immobilization in
rats would require that, in addition to drugs that affect the stomach in a peri-
pheral way, those drugs that have a central effect may also affect the occurrence
of such nmcosa erosions. The effect of atropine and neutralizing substances is
well known [2, 41. Many drugs that work on the central nervous system have autonom-
ic effects, so that it is difficult to decide whether a protective effect is due to
a peripheral or central action. This is not parallel with the central depressive
effect [1].
Our study shared a protective effect for various psychotropic drugs that have
an anticolinergic effect, as for example ami.triptyline, in respect to erosions and
ulcerations in the rat gastric mucosa due to immobilization. other drugs with prac-
tically no autonxdc effect, such as chlordiazepoxide, were ineffective in the exper-
iment. However chlordiazepoxide had the capability of strengthening the effect of
amitriptyline. We have no explanation for this phenomenon but we would like to re-
port it briefly.
Method
	
/616
The experiment was done on male albino rats weighing 60-70 g and belonging to
our own closed, randomized Fuellinsdorf breed. 10 animals at a time were immobilized
* Numbers in the margin indicate pagination in the foreign text.
1
for 16 hours following 48 hours of fasting with superficial ether anesthesia using
the method of Honfils Ill and Hanson and Brodie (2). Then the animals were sacrificed
with ether and the gastric m xxma examined with the naked eye for the presence or ab-
sence of erosions.
The amtrals being treated were given the preparations subcutaneously 30 minutes
prior to the beginning of immobilization. Preparations used were amitriptyline hydro-
chloride and chlordiazepoxide hydrochloride.
Results
All the animals that were not treated presented usually a number of erosions with
one possible exception. Chlordiazepoxide had no effect even in large, highly sedative
doses. The protective effect of amitriptyline depended upon the dosage. When it was
given simultaneously with chlordiazepoxide the protective effect was greater than for
amitriptyline alone;
Preparation	 Dose in	 Protective Protective dose of
mgAg	 effect amitriptyline cal-
subcut.	 (Number of culated on half the
animals from animals showing no
a group of erosion
10 showing
no erosion)
Oontrols	 0,
n
Chlordiazepoxide	 5	 0
10	 n
50	 0
Amitriptyline	
2.5
Tr	
'r	 J,11 m^1^l,ct •_r.
;,5	 h
10
r51	 I^«.r
Amitriptyline (A) +	 A 2,5
Chlordiazepoxide (C)
	
C Il
The dosage effect curves for amitriptyline alone and when combined with chlordiazep- /617
oxide are regressive straight lines running parallel in a statistically reliable way
2
	
Qr 1'0^f`, ►^'C^ IS
(p -4 0.01; correlation coefficient rAC - rA = 0.99; regression coefficient bAC
bA 11.8 1.
The results show that doses of chlordiazepoxide, which are ineffectual by them-
selves, reinforce the protective effect of amitriptyline over a wide dosage range
approximately 1.7 times (1.52 -1.82 in a reliable range of 95%).
Footnote
1. The statistical calculations were graciously performed by W. J. Ziegler.
3
j
a
1. Bonfils, S., Ewtionen and experimentelle Ulcusentstehun . Funktionsablllufe
unter emotion en Be ast►u M.	 s t_n jEwtions and Experimentalmperimental U cer
Occurrence. Functional Processes under Emational Stress. Symposium), Vienna,
1963, pp 127-144 (Karger, Basel 1964).
2. Hanson, H. M. and D. A. Brodie, Use of the R-AsimArvzl Rat Technique for ,Study of
the Antiulcer Effect of Drugs, J. Appl. Physiol. 150, 291-294 (1960).
3. R5hn, F., G. Seybold and R. Pirtkien, Die verschiedenen Formen des experinmtel-
len Ulcus ventriculi bei der Ratte and seine medikament8se Beeinflussung [Var-
ious Forms of Experimental Stomach Ulcer in the Rat and influencing It with
Drugs), Ammimittelforsch. 14, 128-132 (1964).
4. Muller, W. A. and J. Braun, ibid, 203-207.
4


Effect of psychotropic drugs on gastric ulcers induced by immobilization: Increased protective effect of amitriptyline caused by chlordiazepoxide

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