Introduction of GENERAL PRINCIPLES OF PRECLINICAL SCREENING, Types of Screening, Preclinical Studies and its methods,

1. “ GENERAL PRINCIPLES OF PRECLINICAL
SCREENING”
Mrs. Pradnya N. Jagtap
Ms. Sayali S. Chavan
Pune District Education Association’s
Seth Govind Raghunath Sable college of
Pharmacy, Saswad. 1

2. Content
1. Introduction
2. Types of Screening
3. Preclinical Studies and its methods
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3. 1. Introduction
•A laboratory test of a new drug or a series of chemicals, usually
done on animal subjects, to see if they hoped for treatment really
works and if it is safe to test on humans.
• Drugs are Screened to:
Get Pharmacological activity of new/ chemically undefined
substances.
Investigate the function s of endogenous mediators
Measure/ define the toxicity and/or unwanted action.
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4. •Several steps in preclinical trials:
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Identify a drug target
Develop a bioassay
Screen the drug in the assay
Establish Effective and Toxic Doses.
File for approval as an Investigational New drug
(IND)

5. 2. Types of Screening
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Types of
screening
Simple
screening
Blind
screening
Programmed
screening

6. 1. Simple Screening:
 One or 2 similar test to find substances having a
particular property.
 To find the substance are active in a single way.
 No need for battery/series of test.
 Inexpensive & less time consuming.
 Select only suitable method.
 Not sufficiently accrue in result.
 Eg: Hypoglycemic testing: Ability of a compound to
diminish the blood glucose levels.
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7. 2. Blind Screening:
 Only for the series of new chemical substance with no
prior pharmacological history.
 New chemicals entity or isolated naturals.
 Provide a road towards fields of activity if they exist.
 Point out the most potent chemical with interesting
pharmacological activity.
 Toxicological pathway is essential for every library of
compounds.
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8. 3. Programmed Screening:
 Provide information “what compounds are active in what
ways?”.
 A new drug of specific type (known) and/or series of
chemicals is to be investigated for some particular
pharmacological activity. eg: System or organ specific.
 A series of testing program is required to provide
information on the compounds on specific targets .
 Explores main activity and subsidiary activity .
 Potency can be compared with known compounds which
lead the investigator to proceed or to terminate.
 More limited than blind, precision is expected.
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9. 2. Preclinical Studies and its methods
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Preclinical Studies
In-vitro In-Vivo
Receptor
Characterization
Receptor binding assay
Enzyme inhibition
2° messenger assay
Cytotoxic activity
Pharmacologic
al Studies
Toxicological
Study
Efficacy Safety
Dose Conversion
Determination of
Starting Dose

10. 10
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Methods Of Screening
In-vitro Method
 Experimental process in a given procedure which is mainly done
outside the body in a controlled condition.
 Activity (Screening the activity).
 Bioassay (Define the molecular mechanism).
 Toxicity assay (Toxicity of chemicals)
T
ypes
 Biological assay using isolated tisse/organ.
(skeletal/smooth muscles, aorta, heart etc.,)
 Cell culture studies:
Toxicity(cyto) assays
Immunological assays
Cancer cell line studies

11. Chemical Assay using regents:
Antioxidant assays
Xanthine oxidase
Antiglycation activity
Ex-vivo:
DNA : Protein, immunological assay
Experimental process which is performed outside the living
body in an ‘artificial in-vivo environment’
This usually lasting up to 24 hrs.
Experimental process which is performed in the living body
using laboratory animals
In-silico:
Process which is performed on computer or via computer
simulator 11