Dr. Ravindra Gade M.V.Sc 2nd yr scholar, Department of Veterinary Pharmacology & Toxicology College of Veterinary & Animal Sciences, Udgir. MAFSU

1. Department of Veterinary Pharmacology
& Toxicology
Credit seminar on
Dr. Gade Ravindra B.
En.no. V/11/042
M.V.Sc 2nd year
Presented by:
Dr.A.A.Deshmukh Sir
&
Dr. M.K. Patil Mam
Under the guidance of
An overview

2.  Introduction to Reverse Pharmacology (RP)
 History of RP
 Reverse pharmacology in India
 Conventional Vs Reverse pharmacology
 Phases of RP
 Reverse pharmacology in Ayurveda
 Recent developments
 Hurdles
 Future prospectives
 Conclusion.
OUTLINE OF PRESENTATION
2

3. Reverse + Pharmacology =RP
Coming back to Pharmacology
Drug
3

4. • Reverse pharmacology :
The science of integrating documented
clinical/experiential hits, into leads by transdisciplinary
exploratory studies and further developing these leads into
drug candidates by experimental and clinical research
( Hits lead drug candidate )
Ref: Chakrapany et al. 20144

5. Reverse
Pharmacology
Traditional medicine
Morden ScienceMorden medicine
Ref: Dr.Ashutosh Tiwari et al.20146

6.  Conventional path :
 Laboratory to clinic (Bench to Bedside)
Molecule Mice Man /Animal
 Reverse pharmacology path :
 Clinics to laboratories (Bedside to Bench)
Man/Animal Mice Molecule
 SAFTY : Important Starting point
 Efficacy : Matter of validation
Ref: Dr. Siddhartha Datta. 20177

7. Reverse Pharmacology In India
History
 Sir Ram Nath Chopra
-- Father of Indian Pharmacology
--Credit for stimulating interest of Indian chemists and pharmacologist in medicinal plants
 Sir Gananath sen
-- Father of Reverse pharmacology
--laid the foundation of Reverse pharmacology of medicinal plants
 Sir Sen and Bose
 In 1931 demonstrated the antihypertensive and tranquilizing effect of
Rawolfia serpentina.
 Also observed unique side effect such as depression, extra pyramidal
syndrome and peptic ulcer.
Ref: Agnesh Valluri, 2015
Sir Ram Nath Chopra
Sir Gananath Sen
8

8. Ref: Patwardhan B. et al. 2010
9

9. • Average cost & time of discovery, developing and launching a
new drug is consistently increasing without an expected
corresponding increase in the no. of newer, safer & better drugs
• No.NCE(New molecular/chemical entity) declined
• The no. of approval for new drugs has steadily declined.(53 in
1996, 27 in 2016)
Cont..
Ref: Patwardhan B. et al. 2010
- cdsco.nic.in.
10

10. • Increasingly cautious (alertness) regulatory processes
• 10-15 years of investigation period
• Investment of US $ 1 to 1.5 billion
• Pharmaceutical companies - looking beyond conventional drug
discovery
 Natural product drug discovery, Ethnopharmacology, Traditional medicine,
Complementary or alternative medicines are re-emerging as new strategic
option
Ref: Patwardhan B. et al. 2010
11
Cont..

11. • Resistance
• Urgent to find new hits & lead compounds
• Most affected populations have little access to
western medicine(allopathic medicine)
• Use of herbal medicines is the first line
treatment in rural areas.
12
Ref: Dr. Siddhartha Datta. 2017

12. • To understand mechanism of action
• To evaluate clinically the evidence of safety, efficacy, and quality
of drugs /plants
• New drugs from natural products
• To overcome Currently costly, drawn out and attritive process of
drug discovery / development
• Chemical scaffolds for NCEs (New chemical entities)
Ref: Ashwinikumar A.R. et al.2017
13

13. Conventional drug discovery &
development pathway
1)Molecular designing: Structuring & designing of a new
substances
2)Molecular manipulation: Chemical modification of a known
compound
3)Random screening: Screening for different types of activity
4)Bioprospecting : The search for plant and animal species from
which medicinal drugs and other
Drug discovery
Ref: Harpal Singh Sandhu ,2006
14

14. 5)Serendipity: Accidental discovery
6) Active metabolites: one or more active metabolites in body which
has stronger activity than parent
7) Genetic engineering/ Recombinant DNA biotechanology:
Manipulation of genetic elements which result in alterations to proteins
15
Cont..

15. Drug Development
A) Pre-development stage
1) Physiochemical analysis
2) Screening
3) Pharmacological profile
4) Short-term toxicity test
B) Development stage
a) Pre-clinical development
b) Clinical development
Ref: Harpal Singh Sandhu ,2006
16

16. Cont..
Pre-clinical development
1)Pharmaceutical studies –suitable formulation,concentration,stability, shelf life of drug
2)Pharmacological studies-Pharmacokinetic & pharmacodynamic studies
3)Toxicity studies-acute, subsacute, chronic
Clinical development
1) Clinical studies-phase- (I-20 to 50) (II-50 to 300) (III-250 to 1000)
2) Studies of drug residue and safety to humans
3) Studies on environmental safety
4) Getting regulatory approval
5) Post- marketing surveillance
Ref: Harpal Singh Sandhu ,2006
17

17. CONVENTIONAL Vs RP
18
Ref: Patwardhan B. et al. 2010
II only

18. • 1) Experiential phase :
Includes robust (Strong) documentation of
clinical observations of the biodynamic effects of standardized
traditional drugs by meticulous(careful) record keeping.
- Pharmacoepidemiology –resourced information
- Hints from clinical notes
- Classical literature
- Hits from observational therapeutics as well as from single case studies/ case
series
* Experience mostly forms 1st platform of RP.
Ref: Chakrapany et al. 2014
19

19. 2) Exploratory studies:
 for tolerability, drug interactions, dose- range finding in ambulant patients
of defined subsets of the disease
 Paraclinical studies in relevant in vitro and in vivo models to evaluate the
target- activity
Ref: Chakrapany et al.2014
20
Cont..

20. 3) Experimental studies :
 Basic and clinical, at several levels of biological
organization, to identify and validate the reverse
pharmacological correlates of the drug safety and
efficacy
Ref: Chakrapany et al. 2014
21
Cont..

21. • The ayurvedic knowledge database allows drug researchers to start
from a well tested and safe botanical material
• In ayurvedic medicine-Research, clinical experiances,observations or
available data becomes a starting point, in conventional drug research,
it comes at the end.
• With Ayurvedic the normal drug discovery course of laboratory to clinic
actually becomes from clinic to laboratory -- a reverse pharmacology
approach.
• Thus the drug discovery based on Ayurveda follows a “reverse
pharmacology’’ path.
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22. Reverse pharmacology in natural products
23
Phytopharmaceticals
Ref: Patwardhan B. et al. 2008

23. Drugs obtained by the RP path
Ayurvedic Plant Evidence Incidental discoveries
Rauwolifia serpentina
(Sarpagandha)
Anti-hypertensive Anti-depressant
Psoralea caryllifotia
(Bavanchi)
Anti-Vitilligo PUVA – therapy
Berberia aristata
(Indian barberry)
Anti-infective Septic shock, anti- malarial
Picrorrhiza kurroa
(Kutki)
Anti-jaundice Hydrocholerectic, Anti-
asthma
Commiphora wightii
(Gugal)
Anti-arthritic Hypo-lipidemic
Curcuma longa
(Haldi)
Anti-inflammatory Cancer-preventive
Azadirecta indica
(Neem)
Dermatological Anti-cancer, anti-malarial
Phyllanthus emblica
(Amla)
Anti-ageing Free radical scavenger
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24. Reverse pharmacology : India
• Council of Scientific and Industrial Research
NMITLI (New millennium Indian technology leadership initiatives) project
 Has adopted the path of RP
 largest public-private-partnership effort within the R&D domain in the country
• ICMR –
Advanced Centre for Reverse Pharmacology in Traditional Medicine
Kasturba Health Society, Wardha.
where the research focus is on diabetes, musculo-skeletal health, maleria, cancer and neurological
disorders
• A multidisciplinary and multi- institutional team involving
 TIFR(Tata Institute of Fundamental Research, Mumbai)
 KEM Hospital, Mumbai
 C U Shah College of pharmacy, Mumbai
25

25. Recent development
• Best case for reverse pharmacology approach.
• The discovery of Artemisinin for malaria
• Artemisia annua has been used for many centuries in
Chinese traditional medicine as a treatment for malaria
• Result of scientific work based knowledge from
traditional Chinese medicine (TCM)
• It has anticancer, asthma and antioxidant properties
Artemisinin
Ref: Agnesh Valluri, 201526

26. • The best example of bio-prospecting using
traditional knowledge is Reserpine
• the antihypertensive alkaloid from Rauwolfia
serpentina (sarpgandha)
• Result of work carried out by CIBA
pharmaceuticals in India in close collaboration
with Ayurveda experts.
RESERPINE
Ref: Agnesh Valluri . 2015
27

27. • Mucuna pruriens seeds for the treatment of
Parkinson's disease
• Collaboration between Academia and Zandu
Pharmaceutical Works(Mumbai)
• Zandopa is now approved by the Indian FDA
• This standardized, safe and economical natural
product can effectively replace synthetic L-DOPA
formulation
Macuna
Ref: Patwardhan B. et al. 2010
28

28. • The drug candidate (Desoris) is an herbal
beneficiated extract of leaves of Argemone
mexicana
• Under NMITLI project, Lupin Laboratories (India)
attempted development of a single plant based oral
herbal formulation through Reverse Pharmacology
• Novel mechanism of action and effectively
modulates the cellular function leading to psoriatic
lesion healing improvement.
Desoris
Ref: Patwardhan B. et al. 2010
29

29. • Use in Lowering high blood cholesterol, Hardening
of the arteries ,Arthritis,Acne,Skin disease
• Composite drug research program jointly
conducted by ICMR and CSIR of GOI
• Developed from Commiphora mukul taking the
lead from Ayurveda
Guggulipid
30
Ref: Patwardhan B. et al. 2010

30. • A memory enhancer
• Bacopa monnieri (Brahmi) by CDRI , Lukhnow
• Result of 30 years of meticulous research
and development by the Indian government’s Central
Drug Research Institute (CDRI) and is further
supported by Australian clinical trials.
Bacopa
31
Ref: Patwardhan B. et al. 2010

31. Ethanoveterinary formulation for
mastitis
• Made a herbal formulation of A.vera,C.longa &
Calcium hydroxide for mastitis condition
• Promoted by ethno veterinary Herbal training &
Research center, TANUVAS
• Screening of the above functional remedy was done
as a 1st step in reverse pharmacology
32
Ref: Dr. P.Mekala et al.2015

32. • Phytochemical screening revealed alkaloids, saponin, steroids,
carbohydrates,flavaoids,terpenoids, sterols,emodin,diterpens.
• TLC demonstrated phenols, flavoniods & glycosides in optimal
level.
• It is proposed that Phytochemical in the preparation made of
A.vera, C.longa & Calcium hydroxide act synergistically to
effect the clinical case of mastitis
• Further work on this formulation is under the process.
33
Cont..
Ref: Mekala et al.2015

33. • Despite a vast potential and possibilities - very few
success stories
• Most of the work in this fields has remained clinics of
traditional practitioners or confined to academic research
laboratories
• Improper experiential documentation
• Lack of proper identity and implementation of good
laboratory practices
• Cultural prejudice for Alien science
34
Ref: Patwardhan B. et al. 2010
Hurdles

34. Conclusion
• Three main bottlenecks in drug development (Time, money &
toxicity ) can easily addressed by Reverse pharmacology
• It potentiates fast track drug development of newer, safer, and
effective drugs.
• Normal drug development course “laboratory to clinic” actually
becomes “clinics to laboratory‘’ in RP
• So can be concluded that reverse pharmacology research starts
almost where pharmacology ends i.e. to find drugs or herbal
35

35. Reference
• Vaidya, A.D. B. (2006) Reverse pharmacological correlates of ayurvedic drug actions. Indian J.
Pharmacol. 38: 311-315
• Patwardhan, B., Vaidya, A. D. B., Chorghade, M. and Joshi, S. P.,Reverse pharmacology and
systems approaches for drug discovery and development. Curr. Bioact. Compd., 2008, 4, 201–
212.
• Vaidya, A. D. B., Reverse pharmacology – a paradigm shift for new drug discovery based on
Ayurvedic epistemology. In Ayurveda in Transition (eds Muralidharan, T. S. and Raghavan, V.),
AryaVaidya Sala, Kottakal, 2010, pp. 27–38.
• Dr. Ashutosh Tiwari, Reverse pharmacology (www.slideshare.net/drashutoshtiwari/reverse-pharmacology)
• Dr. Siddhartha Dutta, Reverse pharmacology scope in India,
(www.slideshare.net/siddharthadutta8/reverse-pharmacology-scope-in-india)
• Agnesh Valluri , Reverse pharmacology “ A new outlook in the drug development
process”.int,J of allied sci. and clin.Research vol.3(4) 2005
• Ashwinikumar A.R. , Reverse pharmacology, Innovative approaches in drug discovery.
• Patwardhan B. et al. , Indian journal of experimental biology ,Vol.48 ,March 2010,PP.220-227
• Dr.Chakrapany S. et al., Applicability of reverse pharmacology for the antimalarial Ayurveda
herbal drug development: An overview.www.wjpr.net vol.3. issue 4. 2014
• Mekala et al.2015., REVERSE PHARMACOLOGY: ETHNOVETERINARY FORMULATION FOR MASTITIS.,
Indian Veterinary Association Kerala - Proceedings 7th KVSC 2015 - 14th - 15th November 2015
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