1. Presented by :
Mr. Nirav S. Vachhani
M.Pharm Pharmacology (Sem-II)
Guided by:
Dr. Rina H. Gokani
(Associate professor)
S. J. Thakkar pharmacy college, Rajkot.

2. What is CNS ?
• CNS is made of BRAIN and SPINAL CORD.
• The brain is divided into three parts – Forebrain, Midbrain, and
Hindbrain.
• Spinal cord begins from the brain stems and extends till the lowest
end of backbone
• Both the brain and spinal cord contain fluid filled spaces or cavities.
The fluid in these spaces is called cerebrospinal fluid (CSF), and
contains nutrients, hormones, white blood cells to maintain the
CNS.
• Brain and Spinal cord mainly responsible for information
processing, imagination, memory and communication.
© SJTPC, Rajkot. 2

3. © SJTPC, Rajkot. 3

4. Central Neurotransmitters :
• Amino Acids
• Glutamate
• GABA
• Glycine
• Acetylcholine
• Monoamines
• Dopamine
• Norepinephrine
• 5-Hydroxytriptamine
• Peptides
• Nitric oxide
• Endocannabinoids
© SJTPC, Rajkot. 4

5. What are CNS stimulants ?
• Central Nervous System Stimulants may be used to reduce
tiredness and increase alertness, competitiveness and aggression.
• CNS stimulants may be defined as “Drug substance that most
specifically afford an enhancement in excitability either very much
within the different portions of the brain or the spinal cord which
may lead to convulsion.”
• CNS stimulants may be classified as below:
1. Analeptics (convulsant)
• Doxapram (respiratory stimulant)
• Nikethamide (respiratory stimulant)
• Strychnine
• Picrotoxin
• Bicuculline
© SJTPC, Rajkot. 5

6. 2. Psychomotor stimulants
• Amphetamine & Methamphetamine
• Methylphenidate
• Cocaine
• Phentemine
• Fenfluramine
3. General cellular stimulants
• Methylxanthines derivatives
• Caffeine (Caffee)
• Theophylline (Tea)
• Theobromine (Chocolate)
4. Clinical antidepressants
• MAO inhibitors
• Catecholamine reuptake inhibitors
5. Psychotomimetic (Hallucinogenic)
© SJTPC, Rajkot. 6

7. EVALUATION METHODS :
1. Screening of analeptics by PHOTOACTOMETER
2. Strychnine induced convulsion
3. Sand displacement method
4. Runway test
5. Ptosis test
6. Duration of anaesthesia
7. Jiggle cage method
8. Treadwheel method
9. Rotarod method
10. Barbiturate induced sleeping time
© SJTPC, Rajkot. 7

8. 1. Screening of analeptics by PHOTOACTOMETER
• Purpose : CNS stimulants like Amphetamine increase the locomotor
activity in animal.
• Procedure : Mice weighing 20-25 gm are divided in in to 3 groups,
each contain 4 animals.
Control : Saline
Standard : Amphetamine (1 mg/kg I.P.)
Test : Drug to be evaluated
Mice from each group, separately placed in
photoactometer for 10 min duration at the intervals of
30 min till the maximum effect of drug is observed.
• Evaluation : No. of “ cut off ” is compared between groups.
© SJTPC, Rajkot. 8

9. Digital Photoactometer
© SJTPC, Rajkot. 9

10. 2. Strychnine induced convulsion
• Purpose : Drugs like strychnine produce convulsion and
hyperreflexia by inhibiting glycin in CNS.
• Procedure : Groups of 10 mice of either sex with a weight between
18 and 22 gm
mice are injected with 2 mg/kg strychnine nitrate i.p.
in std group and in test group test drug is given
after few minutes convulsions are observed
• Evaluation : Time required to produce convulsion is compared.
• Modifications : Some other drugs produce same effects like
Picotoxin
Pentylenetetrazole
Bucuculine
© SJTPC, Rajkot. 10

11. 3. Sand displacement method :
• Purpose : Drug like Caffeine stimulate the motoractivity in animal by
inhibiting the adenosine transmission in the brain.
• Procedure : A cage with sand is calibrated for amount of sand
displaced per unit time.
Mice weighing 20-25 gm are divided in 3 groups
Control : saline
Standard : caffeine (20 mg/kg orally)
Test : drug to be evaluated
After 1 hour the animal is placed in cage for 15 min
• Evaluation : Volume of sand displaced in each group is compared.
© SJTPC, Rajkot. 11

12. 4. Runway test :
• Purpose : To study the spontaneous activity of CNS stimulants
• Process : Wistar rats of either sex weighing 250-300 gm are grouped
Trained to run in a RUNWAY apparatus for 3 days to
achieve constant time and speed to pass runway
Control : Saline
Standard : Methamphetamine (2 mg/kg I.P.)
Test : Drug to be evaluated
After 30 min of administration of drug test is
performed
• Evaluation : Running time from door opening to pressing the goal
lever was recorded using a microcomputer.
© SJTPC, Rajkot. 12

13. Runway Apparatus:
• The runway apparatus, made using a 5 mm acrylic board, consisted
of a start box (26.5-cm wide, 26-cm long, and 30-cm high),
• A controlled start door (26.5- cm wide, and 30-cm high) that opened
by dropping down a runway (18-cm wide, 180-cm long, and 30-cm
high),
• Priming box (30x30x30 cm).
• A retractable lever (the goal lever) was set at the end of the runway
7 cm above the floor.
• Stimulation was provided from constant current stimulators in the
form of 0.2 ms pulses of 60 Hz alternating current. The stimulation
current was individually adjusted for each rat.
© SJTPC, Rajkot. 13

14. 5. Ptosis test :
• Purpose : Reserpine decreases central sympathetic outflow and
leads to ptosis in eye.
• Procedure:Albino mice of either sex weighing 18-24 gm are grouped
Reserpine is given in all group (4 mg/kg I.P.)
After 2 hr 45 min
Control : saline
Standard : Amphetamine (1 mg/kg I.P.)
Test : drug to be evaluated
After 15 min ptotic rating is made
• Evaluation : 4 for complete ptosis
3 for ¾ ptosis
2 for ½ ptosis
© SJTPC, Rajkot. 14
1 for ¼ ptosis

15. 6. Duration of anesthesia :
• Purpose : Analeptics produces diminution in duration of
anesthesia & also produces respiration stimulation
• Procedure : SD rats weighing 250-350 gm are grouped and
Given Pentobarbital sodium (50 mg/kg I.P.)
After 20 min
Control : Saline
Standard : Methamphetamine (2 mg/kg I.P.)
Test : Drug to be evaluated
After this, animal are placed on its back and recovery
from LRR is checked when animal had righted itself 3
times in 1 min
• Evaluation : Recovery time from LRR is compared
• Modifications :Guinea pig, Rabbit, Mice, Monkey, Cat
© SJTPC, Rajkot. 15

16. 7. Jiggle cage method :
• Purpose : Test is used to evaluate the effect of drug on motor
activity of animal.
• Procedure : Wistar rats of either sex weighing 250-300 gm are
grouped
Control : Saline
Standard : Methamphetamine (2 mg/kg I.P.)
Test : Drug to be evaluated
animal placed in jiggle cage for 10 min to observe
activity changes
• Evaluation : Changes in the movement of animal
• Modification : Rat can also be used
© SJTPC, Rajkot. 16

17. © SJTPC, Rajkot. 17

18. 8. Tread wheel method :
• Purpose : Effect of drug on locomotor activity of rat
• Procedure : Wistar rats of either sex weighing 250-300 gm are
grouped
Control : Saline
Standard : Methamphetamine (2 mg/kg I.P.)
Test : Drug to be evaluated
animal placed in tread wheel for 10 min to observe
activity changes
• Evaluation : Changes in the movement (speed of rotation) of animal
• Modification : Rat can also be used
© SJTPC, Rajkot. 18

19. © SJTPC, Rajkot. 19

20. Tread Wheel
© SJTPC, Rajkot. 20

21. 9. Rota road test :
• Purpose : To evaluate the effect of drug on motor coordination
• Procedure : Mice weighing 18-24 gm are grouped
Control : saline
Standard : Amphetamine (4 mg/kg I.P.)
Test : drug to be evaluated
After 30 min
Animal placed on rotarod
• Evaluation :The time for falling of animal is recorded
© SJTPC, Rajkot. 21

22. Rotarod
© SJTPC, Rajkot. 22

23. 10.Barbiturate induced sleeping time :
• Purpose : To evaluate the effect of drug on motor coordination
• Procedure : Mice weighing 20-30 gm are grouped
Control : Distilled water (10 ml/kg I.P)
Standard : caffeine (20 mg/kg S.C)
Test : drug to be evaluated
After 30 min
Pentobarbitone (40 mg/kg I.P.)
Animal are observed for onset and duration of sleeping
• Evaluation :The sleeping time
• The sleeping time is the time interval between onset of loss of
righting reflex and regain of righting reflex.
© SJTPC, Rajkot. 23

24. REFERENCES :
1. Owolabi OJ, Amaechina FC, and Eledan AB. Central nervous system
stimulant effect of the ethanolic extract of Kigelia africana,
Journal of Medicinal Plants Research, 2008;Vol. 2(2):20-23.
2. Anders A, Medrano A, Garrido N,and Alonso P. GABAergic Drugs
Inhibit Amphetamine-Induced Distractibility in the Rat,
Pharmacology Biochemistry and Behavior, 1997;Vol. 58(1):119–126.
3. Garberg L, and Sandberg F. A Method for Quantitative Estimation
of the Stimulant Effect of Analeptics on the Spontaneous Motility
of Rats, Acta pharmacology and toxicology, 1960;Vol. 16:367-373.
4. Rang HP, Dale MM, Ritter JM, and Flower RJ. CNS stimulants and
psychotometric drug edited Rang and Dale’s Pharmacology, 6th
Edition, UK: Churchhill Livingstone Elsevier 2007; 610-619.
5. Turner RA, Central stimulants in Screening methods in
pharmacology, Academic press Elsevier, 2009;Vol. 1:178-189.
© SJTPC, Rajkot. 24

25. 6. Pickens R. Behavioral Pharmacology: A brief history. In Advances
in Behavioral Pharmacology, edited Thompson T, and Dews PB,
Academic Press, 1977; Vol.1:230.
7. Stong CL. An Amateur's Controlled Experiments Measure the
Effects of a Tranquilizing Drugs on Rats, Science Project
Summary, 1959.
8. Goyal RK, Screening of drugs acting on central nervous system in
Practical in pharmacology, 5 th edition, B. S. Shah prakasan,
Ahmedabad. 2005-2006:121-137.
© SJTPC, Rajkot. 25