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Seminar on
Preclinical screening of new substance for
pharmacological activity
Submitted By-
Shruti Rajeev Gautam
(M.Pharm 1 𝑠𝑡
year )
Guide-
Dr. Vivek Paithankar
Vidya Bharati College of Pharmacy, Amravati.
2019-2020
 Introduction
 CNS stimulants
 Antidepressant Agent
 Antipsychotic Agent
INDEX
A study to test a drug ,a procedure or another medical
treatment in animal
The aim of preclinical screening is to collect data in
support of the safety of new treatment
Preclinical screening are required before clinical trail in
human can be started
Preclinical Screening
CNS stimulant are medicines that stimulant the brain
speeding up both mental and physical process
They increase energy, improve attention and alertness,
and elevate blood pressure, heart rate and respiratory
rate. They decrease the need for sleep, reduce appetite,
improve confidence and concentration, and lessen
inhibitions.
CNS stimulants
CNS stimulants are classified as
1) Analeptic
2) Psychomotor stimulant
3) General cellular stimulant clinical antidepressant
4) Psychotomimetic
1) Screening of analeptic by photoactometer
2) Runway test
3) Treadwheel method
4) Rotarod method
5) Barbiturate induced method
Evaluation method
• Aim:CNS stimulants like amphetamine increase the
locomotors activity
• Procedure
1) Mice weighing 20-25 gm are divided into 3 group
each containing 4 animal
a) Control- saline
b) Standard -amphetamine
c) Test –drug to be evaluated
Screening Of Analeptic By Photoactometer
2) Mice from each group separately placed in
photoactometer for 10 min duration at the interval of
30 min till the more effect of drug is observed
• Evaluation
• No of cut off is compared between group
Screening Of Analeptic By Photoactometer
• Aim: To study the spontaneous activity CNS stimulant
• Animal required :Wister rat
• Equipment required :symmetrical Y shaped runway
• Procedure
1) Wister rat of either sex weighing 250-300gm are grouped
2) Trained to run in a Runway apparatus for 3 days to achieve
a constant speed and time to pass runway
a) Control- saline
b) Standard –methamphetamine
c) Test –drug to be evaluated
Runway Test
4) After 30 min drug of administration of drug test is
performed
Evaluation
Running time from door opening to pressuring the
goal lever was recorded using microcomputer
Runway Test
• Aim :Effect of drug on locomotors activity of rat
• Animal Required :Wistar rat
• Chemical Required: 0.9% Nacl
• Procedure
 Wistar rat of either sex weight 250-300 gm are grouped
1) Control: saline
2) Standard :methamphetamine
3) Test :drug to be evaluated
 Animal placed in tread wheel for 10 min to observe activity change
 Evaluation
 Change in the movement of animal
Tread wheel method
• Aim:To evaluate the effect of drug on motor coordination
• Procedure
1) Mice weighting 18-24gm are grouped
a) Control: saline
b) Standard :methamphetamine
c) Test :drug to be evaluated
2) Animal placed on rota rod
• Evaluation
• Time of mice falling is noted
Rotarod method
• Aim:To evaluate the effect of drug on motor coordinaton
• Animal Required :mice
• Procedure
1) Mice weighing 20-30 gm are grouped
a) Control: distilled water
b) Standard :caffeine
c) Test :drug to be evaluated
2) After 30 min pentobarbitone (40mg/kg)
3) Animal are observed for onset & duration of sleeping
Barbiturate Induced Method
• Evaluation
• The sleeping time is the time interval between onset of
loss of righting reflex & regain of righting reflex
Depression is major affective disorder .it belong to
heterogeneous group of mental disorder characterized by
extreme exaggeration and disturbance of mood which
adversely affect cognition and psychomotor function .
An imbalance in central cholinergic and adrenergic tone
is the critical pathophysiologic mechanism in affective
disorder
Antidepressant Agent
1. Water Wheel Method
2. Learned Helplessness Test
3. Tail Suspension Test
Evaluation method
• This model demonstrate the antidepressant property of the
drug by use of the “Behavioral Despair Activity ”
• the model was proposed by Porsolt
• The purpose of this test that the animal is forced to swim
without any escape in water tank
• Apparatus
1. The apparatus consist of a plexiglas water tank(20cm
×8cm×18cm)with a water wheel in its center
2. The water wheel is made of plexigas shaft (daimeter 3cm,
length 6cm ) on which six paddle
3. The tank filled up to height of 9cm with water at 25 degree
Water Wheel Method
• Procedure
1) The adult rat are forced to swim in a cylinder with no escape
2) The animal become immobilize after initial struggling phase
.the total duration of immobility is measured through out trail
3) Immobility has been equated to despair reaction and rat are
placed back in water after24hr later, they remain immobilize for
a significantly longer time than naïve animal
• Evaluation
a) Duration of immobility is measured in control and animal
treated with various drug
Water Wheel Method
• Aim:In these model a helpless situation is created for the
animal .the rodent are exposed to chronic stress and not allow
to escape from it
• Apparatus: box with a grid floor having plate form
• Procedure
1) Rat with weight 200 to 250 gm. are placed in a
compartment with steel mesh grid floor. repeated shocks are
applied with serves as stress to animal
2) Rat is exposed for shock 1 hr without escaping route .
3) This form the first phase of the model where animal is
exposed to “inescapable shock treatment ”
Learned Helplessness Test
4. In the second phase there is “condition avoidance training
”where after chronic exposure the animal is trained
5. A cue precede the shock and simultaneously a door opened
for safe chamber which is unelectrified and allow the
animal to escape toward it and avoid the noxious stimulus
.this termed as the “escape response ”
Evaluation
 A drug is considered to be effective if the learned
helplessness is reduced and the number of failure to escape
is decreased
Learned Helplessness Test
 This model is modification of the “behavior despair” test
 Animal in this situation alternates between two kind of behavior :
agitation (mobility) and immobility .
 The cumulative immobility time is a measure of the animal degree
of helplessness
Tail Suspension Test
Procedure:
1) The mouse is hang on wire in an upside down posture such
that its nostril touches the water surface in container
2) The animal tries to escape by making vigorous movement
but unable to escape and become immobile.
3) The period of immobility during 5 min observation period
4) The tail suspension monitor is device for screening
antidepressant in mice
Tail Suspension Test
Psychosis is a thought disorder characterized by
disturbance of reality and perception , impaired
cognitive functioning and inappropriate or diminished
affect
Antipsychotic Agent
 Golden Hamster Test
 Catalepsy In Rodent
Evaluation method
 AIM:The aggressive behavior of golden hamsters is suppressed by
neuroleptic in doses which do not impair motor function
 Animal required :Golden Hamster Test
 Procedure
1) Control- vehicle treated
2) Treated-standard drug
3) The animal grouped are placed together in crowded condition in
specially designed cages for at least 14 day
4) The animal develop a character fighting behavior during this
period
 Evaluation
 The suppression of defense reaction is evaluated
Golden Hamster Test
Catalespy in rodent is defined as a failure to correct an
externally imposed , unusual posture over a prolonged
period of time
This is a typical effect of all agent which inhibit
dopaminergic system in the nigorstriatum
Catalespy In Rodent
Procedure
Grouping : group 1: test drug
 group 2: standard drug
Animal are placed inside the translucent plastic boxes
After some time each animal grasped gently around the
shoulder & under the forepaw& placed carefully on
dowel
The amount of time spent at least one fore paw on the
bar determined
Catalespy In Rodent
When the animal remove its paw the time is recorded &
rat is repositioned on the bar
Four trial are conducted for each 30,60, 120 &360 min
An animal is considered catalesptic it remain on the bar
for 60 sec
Evaluation
a) The percentage of catalespy animal is calculated for
each group. ED50 value are calculated for
comparision & elucidation of potency
Catalespy in rodent
 DRUG SCREENING METHODS :SK GUPTA
REFERENCE

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Preclinical screening of new substance for pharmacological activity

  • 1. Seminar on Preclinical screening of new substance for pharmacological activity Submitted By- Shruti Rajeev Gautam (M.Pharm 1 𝑠𝑡 year ) Guide- Dr. Vivek Paithankar Vidya Bharati College of Pharmacy, Amravati. 2019-2020
  • 2.  Introduction  CNS stimulants  Antidepressant Agent  Antipsychotic Agent INDEX
  • 3. A study to test a drug ,a procedure or another medical treatment in animal The aim of preclinical screening is to collect data in support of the safety of new treatment Preclinical screening are required before clinical trail in human can be started Preclinical Screening
  • 4. CNS stimulant are medicines that stimulant the brain speeding up both mental and physical process They increase energy, improve attention and alertness, and elevate blood pressure, heart rate and respiratory rate. They decrease the need for sleep, reduce appetite, improve confidence and concentration, and lessen inhibitions. CNS stimulants
  • 5. CNS stimulants are classified as 1) Analeptic 2) Psychomotor stimulant 3) General cellular stimulant clinical antidepressant 4) Psychotomimetic
  • 6. 1) Screening of analeptic by photoactometer 2) Runway test 3) Treadwheel method 4) Rotarod method 5) Barbiturate induced method Evaluation method
  • 7. • Aim:CNS stimulants like amphetamine increase the locomotors activity • Procedure 1) Mice weighing 20-25 gm are divided into 3 group each containing 4 animal a) Control- saline b) Standard -amphetamine c) Test –drug to be evaluated Screening Of Analeptic By Photoactometer
  • 8. 2) Mice from each group separately placed in photoactometer for 10 min duration at the interval of 30 min till the more effect of drug is observed • Evaluation • No of cut off is compared between group Screening Of Analeptic By Photoactometer
  • 9. • Aim: To study the spontaneous activity CNS stimulant • Animal required :Wister rat • Equipment required :symmetrical Y shaped runway • Procedure 1) Wister rat of either sex weighing 250-300gm are grouped 2) Trained to run in a Runway apparatus for 3 days to achieve a constant speed and time to pass runway a) Control- saline b) Standard –methamphetamine c) Test –drug to be evaluated Runway Test
  • 10. 4) After 30 min drug of administration of drug test is performed Evaluation Running time from door opening to pressuring the goal lever was recorded using microcomputer Runway Test
  • 11. • Aim :Effect of drug on locomotors activity of rat • Animal Required :Wistar rat • Chemical Required: 0.9% Nacl • Procedure  Wistar rat of either sex weight 250-300 gm are grouped 1) Control: saline 2) Standard :methamphetamine 3) Test :drug to be evaluated  Animal placed in tread wheel for 10 min to observe activity change  Evaluation  Change in the movement of animal Tread wheel method
  • 12. • Aim:To evaluate the effect of drug on motor coordination • Procedure 1) Mice weighting 18-24gm are grouped a) Control: saline b) Standard :methamphetamine c) Test :drug to be evaluated 2) Animal placed on rota rod • Evaluation • Time of mice falling is noted Rotarod method
  • 13. • Aim:To evaluate the effect of drug on motor coordinaton • Animal Required :mice • Procedure 1) Mice weighing 20-30 gm are grouped a) Control: distilled water b) Standard :caffeine c) Test :drug to be evaluated 2) After 30 min pentobarbitone (40mg/kg) 3) Animal are observed for onset & duration of sleeping Barbiturate Induced Method
  • 14. • Evaluation • The sleeping time is the time interval between onset of loss of righting reflex & regain of righting reflex
  • 15. Depression is major affective disorder .it belong to heterogeneous group of mental disorder characterized by extreme exaggeration and disturbance of mood which adversely affect cognition and psychomotor function . An imbalance in central cholinergic and adrenergic tone is the critical pathophysiologic mechanism in affective disorder Antidepressant Agent
  • 16. 1. Water Wheel Method 2. Learned Helplessness Test 3. Tail Suspension Test Evaluation method
  • 17. • This model demonstrate the antidepressant property of the drug by use of the “Behavioral Despair Activity ” • the model was proposed by Porsolt • The purpose of this test that the animal is forced to swim without any escape in water tank • Apparatus 1. The apparatus consist of a plexiglas water tank(20cm ×8cm×18cm)with a water wheel in its center 2. The water wheel is made of plexigas shaft (daimeter 3cm, length 6cm ) on which six paddle 3. The tank filled up to height of 9cm with water at 25 degree Water Wheel Method
  • 18. • Procedure 1) The adult rat are forced to swim in a cylinder with no escape 2) The animal become immobilize after initial struggling phase .the total duration of immobility is measured through out trail 3) Immobility has been equated to despair reaction and rat are placed back in water after24hr later, they remain immobilize for a significantly longer time than naïve animal • Evaluation a) Duration of immobility is measured in control and animal treated with various drug Water Wheel Method
  • 19. • Aim:In these model a helpless situation is created for the animal .the rodent are exposed to chronic stress and not allow to escape from it • Apparatus: box with a grid floor having plate form • Procedure 1) Rat with weight 200 to 250 gm. are placed in a compartment with steel mesh grid floor. repeated shocks are applied with serves as stress to animal 2) Rat is exposed for shock 1 hr without escaping route . 3) This form the first phase of the model where animal is exposed to “inescapable shock treatment ” Learned Helplessness Test
  • 20. 4. In the second phase there is “condition avoidance training ”where after chronic exposure the animal is trained 5. A cue precede the shock and simultaneously a door opened for safe chamber which is unelectrified and allow the animal to escape toward it and avoid the noxious stimulus .this termed as the “escape response ” Evaluation  A drug is considered to be effective if the learned helplessness is reduced and the number of failure to escape is decreased Learned Helplessness Test
  • 21.  This model is modification of the “behavior despair” test  Animal in this situation alternates between two kind of behavior : agitation (mobility) and immobility .  The cumulative immobility time is a measure of the animal degree of helplessness Tail Suspension Test
  • 22. Procedure: 1) The mouse is hang on wire in an upside down posture such that its nostril touches the water surface in container 2) The animal tries to escape by making vigorous movement but unable to escape and become immobile. 3) The period of immobility during 5 min observation period 4) The tail suspension monitor is device for screening antidepressant in mice Tail Suspension Test
  • 23. Psychosis is a thought disorder characterized by disturbance of reality and perception , impaired cognitive functioning and inappropriate or diminished affect Antipsychotic Agent
  • 24.  Golden Hamster Test  Catalepsy In Rodent Evaluation method
  • 25.  AIM:The aggressive behavior of golden hamsters is suppressed by neuroleptic in doses which do not impair motor function  Animal required :Golden Hamster Test  Procedure 1) Control- vehicle treated 2) Treated-standard drug 3) The animal grouped are placed together in crowded condition in specially designed cages for at least 14 day 4) The animal develop a character fighting behavior during this period  Evaluation  The suppression of defense reaction is evaluated Golden Hamster Test
  • 26. Catalespy in rodent is defined as a failure to correct an externally imposed , unusual posture over a prolonged period of time This is a typical effect of all agent which inhibit dopaminergic system in the nigorstriatum Catalespy In Rodent
  • 27. Procedure Grouping : group 1: test drug  group 2: standard drug Animal are placed inside the translucent plastic boxes After some time each animal grasped gently around the shoulder & under the forepaw& placed carefully on dowel The amount of time spent at least one fore paw on the bar determined Catalespy In Rodent
  • 28. When the animal remove its paw the time is recorded & rat is repositioned on the bar Four trial are conducted for each 30,60, 120 &360 min An animal is considered catalesptic it remain on the bar for 60 sec Evaluation a) The percentage of catalespy animal is calculated for each group. ED50 value are calculated for comparision & elucidation of potency Catalespy in rodent
  • 29.  DRUG SCREENING METHODS :SK GUPTA REFERENCE