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Introduction
Mixtures of amphetamine and barbiturates have been used in psychiatry for m a n y years in the treatment of anxious or depressed neurotic
patients. Experiments have shown that mixtures of these drugs can be
more effective than either drug alone (Rushton and Steinberg, 1963).
Most of the work has been reported on single acute injections of amphetamine-barbiturate combinations. The present work has been carried out
to discover the effect of chronic treatment with amphetamine and
pcntobarbital sodium on spontaneous motor activity of mice. I n order
to find out whether a beneficial effect is also obtained with other CNS
depressant drugs, the combination of amphetamine with chlorpromazine,
reserpine, chlordiazepoxide and meprobamate has also been studied.
Methods
Male albino mice weighing 20--30 g in groups of 6 were used. Animals
were starved overnight, but were allowed free access to water. All
experiments were carried out between 8 a.m. and 2 p.m.
The effect of chronic treatment with amphetamine sulphate alone or
in combination with drugs like pentobarbital sodium, reserpine, chlorpromazinc (CPZ), chlordiazepoxide and meprobamate, was studied on
spontaneous motor activity (SMA) of mice. The effect of individual drugs
on SMA was also studied; the control group received normal saline.
Three groups were studied with each drug, and drug combination.
2*
20
Drug
Concentration
mg/ml
Dose
mg/kg
Amphetamine administered-hours
after predrug treatment
Normal saline
Amphetamine sulphate
Pentobarbital sodium
Chlorpromazine
Reserpine
Meprobamate
(suspension in 1~
Gum acacia)
Chlordiazepoxide
(suspension in polyethylene glycol)
0.90/0
0.15
1.2
0.0001
0.01
1 ml/100 g
1.5
12
0.001
0.10
--together
11/2
51/2
2.5
25
1/2
0.1
1/2
21
Table 2. E]/ect o/ amphetamine sulphate (1.5 mg/kg i.p.) with pentobarbital sodium
Normal saline
~ decrease in
activity
Amphetamine
~ increase in
activity
Pentobarbital
~ decrease in
activity
Amphetamine ~pentobarbital ~
increase in
activity
1
2
3
4
5
6
7
8
9
10
14
12
16
16
18
17
15
17
11
14
19
18
23
22
26
29
34
38
31
35
15
15
14
16
12
11
8
8
16
16
21
34
45
65
50
76
57
83
96
90
Normal saline
~ decrease in
activity
Amphetamine
~ increase in
activity
Chlorpromazine Amphetamine -~
~ decrease in chlorpromazine
activity
~ increase in
activity
i
2
3
4
5
6
7
8
9
10
14
11
12
14
15
12
14
17
11
12
17
19
30
36
37
39
42
33
37
47
9
4
7
8
3
8
6
3
12
8
33
55
68
64
71
80
80
82
87
84
22
Table 4. Effect o/amphetamine sulphate (1.5 mg/kg i.p.) with reserpine (0.1 mg/kg)
Normal saline
~ decrease in
activity
Amphetamine
0/9 increase in
activity
Reserpine
~ decrease in
activity
Amphetamine ~reserpine ~
increase in
activity
1
2
3
4
5
6
7
8
9
10
17
14
17
18
20
21
25
18
18
25
33
22
36
41
53
60
67
66
73
73
22
31
18
21
19
23
26
32
40
32
31
28
60
78
85
122
168
232
219
259
Normal saline
~ decrease in
activity
Amphetamine
~ increase in
activity
~r
Amphetamine -b
~ decrease in meprobamate ~
activity
increase in activity
1
2
3
4
5
6
7
8
9
10
11
15
10
16
15
18
18
24
21
24
30
18
40
56
60
53
49
51
60
70
25
30
21
24
18
21
23
21
23
27
33
49
52
66
74
87
72
68
84
84
T h e c o m b i n a t i o n of a m p h e t a m i n e w i t h r e s e r p i n e p r o v e d m o r e effective
t h a n a m p h e t a m i n e alone. T h e effect g r a d u a l l y i n c r e a s e d a n d on t h e
10th d a y a c t i v i t y i n c r e a s e d b y 259~ (Table 4).
E//ect of Amphetamine in Combination with Meprobamate. N o r m a l
saline d e c r e a s e d a c t i v i t y b y 10 t o 24~ o n d a i l y a d m i n i s t r a t i o n . A m p h e t a m i n e i n c r e a s e d a c t i v i t y b y 18 to 70~
M e p r o b a m a t e (25 m g / k g )
d e c r e a s e d SMA b y 18 t o 300/0. A m p h e t a m i n e in c o m b i n a t i o n w i t h
m e p r o b a m a t e p r o d u c e d g r e a t e r effect t h a n t h e a m p h e t a m i n e alone.
H o w e v e r , t h i s increase was n o t s t a t i s t i c a l l y significant (Table 5).
E//ect o/Amphetamine with Chlordiazeproxide on S M A . N o r m a l saline
d e c r e a s e d S M A b y 10 t o 230/0 . A m p h e t a m i n e i n c r e a s e d t h e a c t i v i t y b y
31 t o 50~ t h e m a x i m u m effect being seen on t h e 1st d a y . Chlordiazepo x i d e (1 m g / k g ) d e c r e a s e d a c t i v i t y b y 5 t o 30~ on d a i l y a d m i n i s t r a t i o n
23
Normal saline
~ decrease in
activity
Amphetamine
~ increase in
activity
1
2
3
4
5
6
7
8
9
10
13
10
15
16
18
15
13
16
23
21
50
34
33
33
33
31
47
42
45
~
Chlordiazepoxide ~
decrease in
activity
5
11
10
14
13
15
21
30
28
24
Amphetamine -~
Chlordiazepoxide
~ increase in
activity
60
36
54
63
66
66
65
65
77
68
24
25
Prof. U. K. Sheth
Department of Pharmacology
Seth G. S. Medical College
Parel, Bombay-12, India