Reverse pharmacology is an approach to drug discovery that begins with clinical observations of traditional medicines and then uses exploratory and experimental studies to validate efficacy and safety. It reverses the conventional path of discovery from the laboratory to clinics. Key advantages include starting with clinically tested botanicals, reducing costs and time, and leveraging an experiential database of traditional medicines. Challenges include few success stories adopted by industry. Increased awareness and innovative solutions inspired by traditional knowledge may help accelerate discovery through the reverse pharmacology approach.

1. REVERSE PHARMACOLOGY
&
DRUG DISCOVERY
ILHAR HASHIM, M PHARM-CLINICAL RESEARCH
NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH (NIPER), MOHALI, INDIA-
160062

2.  DEFINITION:
Reverse pharmacology is the science of
integrating documented clinical/experiential
hits, into leads by transdisciplinary
exploratory studies and further developing
these into drug candidates by experimental &
clinical research

3.  SCOPE:
The scope of reverse pharmacology is to
understand the mechanisms of action at
multiple levels of biological organization and
to optimize safety, efficacy and acceptability
of the leads in natural products, based on
relevant science

4. CONCEPT OF REVERSE PHARMACOLOGY
 The traditional knowledge inspired reverse
pharmacology relates to reversing the routine
‘laboratory to clinic’ progress of discovery
pipeline to ‘clinics to laboratories’.
 The ayurvedic knowledge database allows
drug researchers to start from a well tested
and safe botanical material.
 Thus in ayurvedic medicine research, clinical
experiences, observations or available data
becomes a starting point.
 In conventional drug research, it comes at the
end.

5. CONCEPT OF REVERSE PHARMACOLOGY
 Thus the drug discovery based on ayurveda
follows a ‘reverse pharmacology’ path.
 Conventional drug discovery path
Molecule Mice Men
 Reverse pharmacology path
Man Mice Molecule
 In this process ‘safety’ remains the most
important starting point and the ‘efficacy’
becomes a matter of validation.

6. CONCEPT OF REVERSE PHARMACOLOGY

7. CONCEPT OF REVERSE PHARMACOLOGY
Traditional medicine
Modern medicine Modern science
 Reverse pharmacology is ‘Transdisciplinary’.
 Efficient discovery engine

9. DRUG DISCOVERY:CURRENT SCENARIO
 The incredible growth of pharmaceutical
companies due to the discovery of blockbuster
drugs is coming to an end.
 The average cost and time of discovering,
developing and launching a new drug is
consistently increasing without an expected
corresponding increase in the number of newer,
safer and better drugs.
 New molecular entities produced per company
have declined.

10. DRUG DISCOVERY:CURRENT SCENARIO
 The strategies that awarded success during
the past may not guarantee the same in the
future.
 So the industry is facing a major challenge to
sustain and grow, which is resulting in many
merges, acquisitions or closures.

11. PHASES OR DOMAINS OF REVERSE PHARMACOLOGY

12. PHASES OR DOMAINS OF REVERSE PHARMACOLOGY
 So reverse pharmacology is transdisciplinary
aspect that is comprised of three phases or
domains.
1. Experiential
2. Exploratory
3. Experimental

13.  EXPERIENTIAL :
This phase includes robust documentation
of clinical observations of the biodynamic
effects of standardized ayurvedic drugs by
meticulous record keeping.

14.  EXPLORATORY :
This phase includes the studies for tolerability,
drug interactions, dose range finding in
ambulant patients of defined subsets of the
disease and paraclinical studies in relevant
invitro & invivo models to evaluate the target
activity.

15.  EXPERIMENTAL :
In basic & clinical, at several levels of
biological organisation, to identify and
validate the reverse pharmacological
correlates of ayurvedic drug safety and
efficacy.

16. DRUGS FROM REVERSE PHARMACOLOGY PATH
ARTEMISININ
 The artemisinin was developed from the herb
Artemisia annua that has been used for
many centuries in Chinese traditional
medicine as a treatment for fever and
malaria.
 Now artimisinin and its derivatives offer a
promise as a totally new class of
antimalarials.

17. DESORIS
 This drug candidate is a herbal beneficiated
extract of a single plant that has a novel
mechanism of action and effectively
modulates the cellular function leading to
psoriatic lesion improvement.
 Lupin commenced the phase1 clinical trial in
september 2004 successfully completed it.
 If successful, the resulting treatment with
Desoris only cost US $ 50, when compared
to new US $ 20,000 antibody injection

18.  Rauwolfia alkaloids for hypertension.
 Psoralens in Vitiligo.
 Holarrhena alkaloids in Amoebiasis.
 Picrosides in hepatic protection etc…

19. REVERSE PHARMACOLOGY: HURDLES
 Despite a vast potential and possibilities very
few success stories are available till now.
 Most of the work in this field has remained
within clinics of traditional practitioners and
are not taken by industries that are strong in
research and development.
 The pharmaceutical industry needs many
more successes like artemisinin & reserpine.

20. FUTURE PERSPECTIVES
 Many countries are increasingly aware of the
value of their traditional knowledge.
 Global pharmaceutical industry is looking for
innovative solutions to re-activate and re-
energize their discovery pipeline.
 Therefore, innovative approaches inspired by
traditional knowledge will remain important to
fast forward the discovery process

21. CONCLUSION
 Traditional knowledge and experiential database
can provide new functional leads to reduce time,
money and toxicity – the three main hurdles in the
drug development .
 These records are particularly valuable since
those medicines have been effectively tested for
thousands of years on people .
 With the reverse pharmacology approach, the
normal drug discovery course of ‘Laboratory to
clinics’ becomes from ‘Clinics to Laboratories’.

22.  India with its pluralistic health care system offers
immense opportunities for natural product drug
discovery and development based on traditional
knowledge and clinical observations.
 So reverse pharmacology approaches need to be
further developed and optimized as novel means
for fast track drug discovery and development of
newer, safer & effective drugs.

23. THANK YOU