Course

Unit 1

UNIT I-Introduction to human disease models 5 hours

1. General principles of preclinical screening using invitro, invivo models (1 hours)
2. Validation requirements for screening models (1hour)
3. Different types of controls and importance of controls in preclinical studies (1hour)
4. Transgenic animals: Production, maintenance and (1hour)
5. Dose selection, Calculation and Preparation of drug solution/suspensions (1hour)

Unit 2

UNIT II Screening models in CNS Pharmacology 10 hours

1. Behavioral and muscle coordination (1 hour)
2. CNS stimulants and depressants, anxiolytics (2 hours)
3. Anti-psychotics (1 hour)
4. Anti epileptics and nootropics (2 hours)
5. Drugs for neurodegenerative diseases like Parkinsonism, Alzheimer’s and multiple sclerosis (3 hours)

2) Drugs used migraine (1hour)

Unit 3

Unit III Screening models in Cardiovascular Pharmacology: 6 hours Antihypertensives, antiarrhythmics, antianginal, anti-atherosclerotic agents and diuretics, anti-stroke agents (5 hours)

Drugs acting on Autonomic Nervous System (1hour)

Unit 4

Unit IV Screening models in respiratory and reproductive pharmacology 6 hours

Anti-asthmatics, drugs for COPD and anti-allergic agents (3 hours) Aphrodisiacs and antifertility agents (3 hours)

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Unit 5

Unit V Screening models for anti-inflammatory and gastrointestinal agents 7 hours

Analgesics, anti-inflammatory and antipyretic agents (3 hours) Antiulcer, anti-colitis, anti-emetic, anti-diarrheal and laxatives. (4 hours)

Unit 6

Unit VI Screening models for drugs used in metabolic disorders, cancer and immunotherapy 6 hours

Anti-diabetic, anti-dyslipidemia agents, hepato-protective screening methods. (3 hours) Anticancer agents (2 hours)

Immunomodulators; Immunosuppressants and immunostimulants (1 hour)

Unit 7

UNIT VII Alternative models and extrapolation of preclinical data 5 hours

1. Limitations of animal experimentation and significance of alternate animal experiments 1 hour
2. Alternative models for drug screening include lower animal models, 3D cell culture and organ on chip models. 2 hours
3. Extrapolation of invitro data to preclinical and preclinical to humans 1hour

This subject is designed to impart the knowledge on preclinical evaluation of drugs which plays major role in drug discovery and development. The subject content helps the student to understand various species of animals including genetically modified animals used in preclinical experiments, the importance of their maintenance and the guidelines involved in it. It also deals with the standard regulatory requirements for preclinical studies, importance of various controls as well as validation requirements for various screening models. The subject gives detailed description on established in- vitro and in-vivo models used in the screening of various disease conditions.

It also discusses the limitations of these screening models and various alternatives to animal models used and being developed for preclinical screening. The subject also discusses various methods as well as challenges involved in extrapolation of these data to clinical studies.

Upon successful completion of the course, the student shall be able to,

KNOWLEDGE

K1: Explain the regulations and ethical requirements involved in usage of experimental animals K2: Explore various screening methods involved in the drug discovery process

K3: Justify the use of various animals in the drug discovery process K4: Predict the limitations of animal models

K5: Analyze the role of various assays used in pharmacological experiments K6: Recommend various alternative models for animal experiments

SKILL

S1: Employ the regulations and ethical requirement for the usage of experimental animals S2: Apply good laboratory practices in maintenance and handling of experimental animals S3: Perform various preclinical screening tests using appropriate in vivo and in vitro models.

S4: Analyze research articles to evaluate the applicability of different screening models in research. S5: Develop skills in designing experiments and protocols for various pharmacological screenings.

S6: Correlate preclinical data to potential human applications, understanding the challenges in extrapolation.

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ATTITUDE

A1: Appreciate ethics in pharmacological research A2: Collaborate and work in team

A3: Update new advancements in scientific research

A4: Display strong commitment of honest and systematic documentation of study results A5: Exhibit responsibility towards society

A6: Express curiosity in newer research developments

Reference books

1. Burn H, D. J. Finney, and L. G. Goodwin. Biological standardization. 2nd edition. Oxford University Press; 2011.
2. Turner Screening methods in pharmacology. Volume II. Elsevier; 2013.
3. Laurence R. & Bacharach A. L. Evaluation of drug activities: pharmacometrics. Volume 1. Academic Press; 2011.
4. Schwartz, Methods in pharmacology. Volume 1 Appleton-Century-Crofts; 2013.
5. N.Ghosh. Fundamentals of experimental Pharmacology, 7^th edition. Hilton and Company; 2019
6. MacLeod, J. Pharmacological Experiments on Intact Preparations. Drug discovery and Evaluation. 3^rd edition. E. and S. Livingstone; 2011
7. Gupta K. Drug screening methods: preclinical evaluation of new drugs. 2^nd edition. Jaypee. 2016
8. Kulkarni K. Hand book of experimental pharmacology. 4^th edition. Vallabh prakashan; 2015.
9. Kulkarni K. Practical Pharmacology and Clinical Pharmacy. 3^rd Edition. Vallabh Pub; 2008
10. Gross Animal models in cardiovascular research. 2^nd edition. Springer Science & Business Media; 2009.
11. Tapan Kumar Chatterjee . Rodents for Pharmacological Experiments. BSP Books; 2018.
12. Medhi B, & Prakash Practical manual of experimental and clinical pharmacology. Jaypee Brothers; 2010.

Journals:

1. European Journal of Pharmacology. Science Direct (https://www.sciencedirect.com/journal/european-journal-of-pharmacology)
2. Inflammation research. Springer Link (https://www.springer.com/journal/11)
3. Scientific reports (https://www.nature.com/srep/)
4. Thieme (https://www.thieme.in/pharmacopsychiatry)
5. Pharmacological research. Science Direct (https://www.journals.elsevier.com/pharmacological-research)
6. Inflammation. Springer Link (https://www.springer.com/journal/10753)

Assignments:

1. Animal house visit and compilation of reports including studies presently conducted in animal house.
2. Present research paper on in vitro and in vivo screening of any natural product for its anticancer activity.
3. List out the objectives, function, and composition of Steps to be followed for animal study approval in IAEC
4. Presentation on Research Paper based on screening of various classes of
5. Patient derived organoids as model for anticancer drug discovery
6. Design methodology for screening of a compound which is found to have neuroprotective effect.
7. Common laboratory animals: Description, handling and applications of different species and strains of animals.
8. Anesthesia and euthanasia of experimental Maintenance and breeding of laboratory animals.
9. CCSEA guidelines to conduct experiments on Good laboratory practice.
10. Screening of antiviral drugs
11. Schedule Y guidelines for conducting acute toxicity studies for parenteral preparations 249