Rationale of reverse pharmacology

[Guest guest]

Dear Dr. Smita Mali

Its good to read your valuable posting on reverse pharmacology along with significant examples. Related to Rauwolfia serpentina, I would like to add that it was firstly Prof. Saleemuzzaman Siddiqui who worked on Rauwolfia serpentina during 1920s when Hakim Ajmal Khan (a renowned Unani Physician) suggested him to work on this plant roughly a decade before Sen and Bose (famous scientists of Kolkata). The alkaloid Ajmalcine (or Ajmalin) is named by Saleemuzzaman Siddiqui after the name of Hakim Ajmal Khan. The isolation of the alkaloid was done at the Department of Chemistry of our University.

Regards,

S. Ziaur Rahman

Rationale of reverse pharmacology

Hello NetRUMians,

Basic pharmacology starts with various sources of medicine. Plants claim its first place in the list. Clinical uses found were serendipitous in some of the cases. In India Ayurveda, the science in itself is known and being practiced since ages. Also Unani, Homeopathy, Chinese medications are being followed in different regions worldwide.

These experiences can be used to derive hits for new medicine development. Because of the long term use being followed in community we get the assurance of safety for these new molecules and hence shortens the drug development path. Following are the examples of plant derivatives leading to the establishment of group of medicine in various treatments or discovering the target for the same.

Medicinal plant

Clinical effect

Experimental correlate

Curare tomentosum

Paralysis and death

Neuromuscular block

Papaverum somniferum

Analgesia

Opioid receptors

Physostigma venenosum

Ordeal poison

Anticholinesterase

Cinchona officinalis

Antipyrexia

Antimalarial

Digitalis purpurea

Dropsy relief

Na+,K+-ATPase

Salix alba

Fever and pain relief

Prostaglandins

Strychnos nuxvomica

CNS stimulant

Glycinergic receptors

Rauwolfia serpentina Benth (Sarpagandha)

Sen and Bose not only showed the antihypertensive effects of R. serpentina, but were also astute clinicians to note certain side effects such as Parkinsonism, depression, gynecomastia, acid peptic symptoms and so on. There was almost a gap of two decades in discovering the pharmacological basis of these actions. The storage vesicles are rendered dysfunctional as a result of their interaction with reserpine and the depletion of biogenic amines explained the actions by mechanistic correlates. As a spin off of the side effects of R. serpentina, several new drugs were developed such as L-dopa, antidepressants, bromo-ergocriptine, and H 2 receptor blockers and so on. The alkaloids of R. serpentina, reserpine and ajmalcine, have served as research tools in many experiments.

Regards,

Smita Mali

[Guest guest]

Hello Sir,

Indeed it is very good information regarding reserpine. This medicine as said has not only given one of the way to treat the hypertension but also due to keen observations of the outcomes shown targets for other major diaseases. This very protocol defines the reverse pharmacology. It is definitely to be proud of that milestone event occured at your university.

Ayurveda, Unani are traditional medicines being practiced in India. Many academia in the country are dedicated to work on research activity related to these fields. I request our senior NetRUMians to come forward and enlighten the group by sharing information regarding RP at their places.

Regards,

Smita

From: ibnsinaacademy <ibnsinaacademy@...>Subject: Re: Rationale of reverse pharmacologynetrum Date: Wednesday, 26 March, 2008, 12:16 AM

Dear Dr. Smita Mali

Its good to read your valuable posting on reverse pharmacology along with significant examples. Related to Rauwolfia serpentina, I would like to add that it was firstly Prof. Saleemuzzaman Siddiqui who worked on Rauwolfia serpentina during 1920s when Hakim Ajmal Khan (a renowned Unani Physician) suggested him to work on this plant roughly a decade before Sen and Bose (famous scientists of Kolkata). The alkaloid Ajmalcine (or Ajmalin) is named by Saleemuzzaman Siddiqui after the name of Hakim Ajmal Khan.. The isolation of the alkaloid was done at the Department of Chemistry of our University.

Regards,

S. Ziaur Rahman

Rationale of reverse pharmacology

Hello NetRUMians,

Basic pharmacology starts with various sources of medicine. Plants claim its first place in the list. Clinical uses found were serendipitous in some of the cases. In India Ayurveda, the science in itself is known and being practiced since ages. Also Unani, Homeopathy, Chinese medications are being followed in different regions worldwide.

These experiences can be used to derive hits for new medicine development. Because of the long term use being followed in community we get the assurance of safety for these new molecules and hence shortens the drug development path. Following are the examples of plant derivatives leading to the establishment of group of medicine in various treatments or discovering the target for the same.

Medicinal plant

Clinical effect

Experimental correlate

Curare tomentosum

Paralysis and death

Neuromuscular block

Papaverum somniferum

Analgesia

Opioid receptors

Physostigma venenosum

Ordeal poison

Anticholinesterase

Cinchona officinalis

Antipyrexia

Antimalarial

Digitalis purpurea

Dropsy relief

Na+,K+-ATPase

Salix alba

Fever and pain relief

Prostaglandins

Strychnos nuxvomica

CNS stimulant

Glycinergic receptors

Rauwolfia serpentina Benth (Sarpagandha)

Sen and Bose not only showed the antihypertensive effects of R. serpentina, but were also astute clinicians to note certain side effects such as Parkinsonism, depression, gynecomastia, acid peptic symptoms and so on. There was almost a gap of two decades in discovering the pharmacological basis of these actions. The storage vesicles are rendered dysfunctional as a result of their interaction with reserpine and the depletion of biogenic amines explained the actions by mechanistic correlates. As a spin off of the side effects of R. serpentina, several new drugs were developed such as L-dopa, antidepressants, bromo-ergocriptine, and H 2 receptor blockers and so on. The alkaloids of R. serpentina, reserpine and ajmalcine, have served as research tools in many experiments.

Regards,

Smita Mali

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[Guest guest]

Hello,

After having look at the simplified diagrams here is the description of the steps involved in RP

Reverse pharmacology from clinic to laboratory:

Ø Clinical wisdom: Most important, starts with humans and covers the clinical and laboratory documentation of novel biodynamic actions. In observational therapeutics, any effect of interest, known or unknown gets documented in a robust manner, if essential even with sophisticated objective laboratory monitoring.

Ø National consultations, Pharmacoepidemiology: Various traditional medicines can be taken into account after its recording done at different levels in the society so as to derive useful hits.

Ø Bioprospecting: It is a more positive term and commonly used by supporters of commercialization of traditional medicines. While there is still no hard definition, media and academia use this less pejorative term when speaking about endeavors to capitalize on indigenous knowledge of natural resources. However, bioprospecting may also describe the search for previously unknown compounds in organisms that have never been used in traditional medicine

Ø Quality control methods: Most of the traditional medicines are prepared and used based on the traditional concepts of Ayurveda, Siddha and other traditional philosophies for disease identification and their relation of the physicochemical properties of the medicines. Hence the method of quality control should also take the above properties in to consideration while assessing the quality of the traditional medicines with out deviating from the basic philosophy.

Ø Chemoprofile: Understanding chemical structure, active and supporting groups of the isolated compound.

Ø Herboprint: The herbal samples will be extracted into different aqueous and non-aqueous solvents. The extracts will be subjected to preparative chromatographic separation on a large scale and pure compounds will be isolated the single molecules will be analyzed using different analytical instruments for structure establishment. Interpretation of the fingerprint having molecules at different retention times and their retention time and their UV spectrum properties along with polarity is providing information about the chemical and therapeutic clinical properties of the material under analysis. Thus the Herboprint will be useful in different drug discovery.

Further procedures are well known steps in our clinical research.

Ø Disease focus

Ø Pharmaceutics

Ø Pre clinical studies

Ø Protocol development

Ø Phase I RCT

Ø Data consolidation

Ø Phase II and Phase III

Ø Pharmacodynamics

Regards,

Smita Mali

[Guest guest]

Hello Sir,

This post is to further elaborate useful information given by you.

Traditional Knowledge Digital Library is a knowledge repository of the traditional knowledge. Setup by the Indian government, the objective of this library is to protect the ancient and traditional knowledge of the country from exploitation such as bio-piracy and unethical patents.

Data on 65,000 formulations in Ayurveda, 70,000 in Unani and 3,000 in Siddha had already been put in the TKDL, and is being made available in five languages — English, German, French, Spanish and Japanese.

The data relating to only 7,000 formulations each in Unani and Siddha, and 1,500 postures in yoga remained to be included and the entire process was expected to be completed by December, 2008.

TKDL is a collaborative project of

National Institute of Science Communication and Information Resources (NISCAIR), located at New Delhi, India, is one of the premier information science institutes in India.

the Department of Ayurveda, Yoga & Naturopathy, Unani, Siddha and Homeopathy (Dept of AYUSH), in the central Ministry of Health and Family Welfare and,

The Department of Industrial Policy and Promotion in the central Ministry of Commerce and Industry.

The project was taken up in 2001.

Following URL gives information regarding traditional knowledge and its security.

http://www.slais.ubc.ca/COURSES/libr500/05-06-wt2/www/D_Ionson/index.htm

Regards,

Smita Mali>> The combined project of NISCAIR (CSIR) and Department of AYUSH (MoH & FW) on Traditional Knowledge Digital Library (TKDL) will help more in finding and providing a "lead" to all research scholars interested in reverse pharmacology. As far as I know TKDL of Ayurvedic Medicine is almost complete while of Unani and Siddha Medicine is going on at a speedy pace.> > S. Ziaur Rahman

[Guest guest]

Hello,

Dr. ziaur has given the good source i.e. TKDL as database for start of reverse pharmacology research. Being source on one hand it also works for the protection of intellectual property rights. Please find the attachments, one of which gives basis for the establishment of TKDL while other gives the proforma to be followed to get assess of TKDL.Regards,

Smita

From: ibnsinaacademy <ibnsinaacademy@...>Subject: Re: Rationale of reverse pharmacologynetrum Date: Wednesday, 26 March, 2008, 12:33 AM

 The combined project of NISCAIR (CSIR) and Department of AYUSH (MoH & FW) on Traditional Knowledge Digital Library (TKDL) will help more in finding and providing a "lead" to all research scholars interested in reverse pharmacology. As far as I know TKDL of Ayurvedic Medicine is almost complete while of Unani and Siddha Medicine is going on at a speedy pace.

S. Ziaur Rahman

Rationale of reverse pharmacology

Hello,

Following is the abstract of review article “Ayurveda and natural products drug discovery†by Bhushan Patwardhan, Ashok D. B. Vaidya and MukundChorghade which nicely explains ayurveda, new drug discovery and place of reverse pharmacology.

This review attempts to portray the discovery and development of medicine from galenical to genomical, with a focus on the potential and role of ayurveda. Natural products, including plants, animals and minerals have been the basis of treatment of human diseases.

Indigenous people derived therapeutic materials from thousands of plants; however discovering medicines or poisons remains a vital question. Ayurveda is a traditional Indian medicinal system being practiced for thousands of years.. Considerable research on pharmacognosy, chemistry, pharmacology and clinical therapeutics has been carried out on ayurvedic medicinal plants.

Many of the major pharmaceutical corporations have renewed their strategies in favour of natural products drug discovery and it is important to follow systems biology applications to facilitate the process. Numerous drugs have entered the international pharmacopoeia through the study of ethnopharmacology and traditional medicine. For ayurveda and other traditional medicines newer guidelines of standardization, manufacture and quality control are required. Employing a unique holistic approach, ayurvedic medicines are usually customized to an individual constitution.

Traditional knowledge-driven drug development can follow a reverse pharmacology path and reduce time and cost of development. New approaches to improve and accelerate the joint drug discovery and development process are expected to take place mainly from innovation in drug target elucidation and lead structure discovery. Powerful new technologies such as automated separation techniques, high-throughput screening and combinatorial chemistry are revolutionizing drug discovery. Traditional knowledge will serve as a powerful search engine and most importantly, will greatly facilitate intentional, focused and safe natural products research to rediscover the drug discovery process.

Regards,

Smita Mali

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<p align=center style='text-align:center'><b><span style='font-size:18.0pt;

font-family:Arial;color:red'>Traditional Knowledge Digital Library

(TKDL)</span></b></p>

<p><b> & nbsp;</b></p>

<p><b>ABSTRACT</b></p>

<p><i>Describes the usefulness of the prposed digital library in the prevention

of granting of wrong patents based on Indian Traditional Knowledge (ITK),

dissemination of information about ITK on medicines and broadening the scope of

research on Ayurveda.</i> </p>

<p><b>KEYWORDS:</b> Ayurveda, Digital Library, Traditional Knowledge </p>

<p>Protection and preservation of traditional knowledge have been a matter of

concern to the developing countries in general and India in particular. India

successfully contested the grant of patents for non-original inventions in its

traditional knowledge systems, i.e. turmeric for wound heeling (US Patent No.

5401540), neem for anti-fungal properties (EPO Patent No, 0436257), Basmati,

etc. Cancellation of these patents established that (i) it is feasible to

oppose grant of wrong patents at international level ;and (ii) it is extremely

expensive and time consuming to contest the wrong patents at international

level. Cancellation of the patent for turmeric took about 2 years whereas that

for neem it took 5 years. Grant of wrong patents at international level happens

owing to non-availability of information in a language known to International

Patent Examiner and also, the information not being in retrievable form.

Therefore, need was felt to adopt a practical and scientific approach to the

problem of grant of wrong patents in our traditional knowledge systems at

international level. </p>

<p>The Department of Indian System of Medicine and Homoeopathy (ISM & amp;H)

constituted an inter- disciplinary task force consisting of Ayurveda experts

from Central Council of Research in Ayurveda and Siddha (CCRAS), Banaras Hindu

University (BHU), Department of ISM & amp;H, patent examiners from the Office of

the Controller General of Patent, Design and Trade Marks (CGPDTM), information

technology experts from National Informatics Centre (NIC), and scientists from

Council of Scientific and Industrial Research (CSIR), under the Chairmanship of

Mr V K Gupta, Director, National Institute of Science Communication (NISCOM),

New Delhi. </p>

<p>The Task Force carried out an extensive search on international patent

databases and found that more than five thousand patent references on ninety

medicinal plants appeared in United States Patent and Trademark Office (USPTO)

databases alone. Out of these references on ninety medicinal plants, 80% were

on seven medicinal plants of Indian origin. The extensive study done on 762

patents granted on medicinal plants by USPTO revealed that more than 45%

patents could be categorized as patents belonging to traditional knowledge

system. Several illustrative cases were identified, such as the use of turmeric

for the treatment of skin disorders; herbal compositions and their use as

hypoglycemic agent for its anti-viral effect, and in the treatment of diabetes,

musculoskeletal diseases, etc for which direct references of prior art are

available in Ayurveda. The Task Force devised a methodology for creating a

Traditional Knowledge Digital Library (TKDL) based on fifteen well- known

Ayurvedic books which are being referred at undergraduate and postgraduate

level courses in Ayurveda and are also well-known to Ayurvedic practitioners.

These books could be easily purchased by any member of public and library

(Indian or foreign ) at a total cost of Rs 15,000. </p>

<p>The TKDL concept and methodology were also discussed with eminent experts in

Ayurveda with respect to the advantages and disadvantages of creating such a

digital library in public domain. Eminent Ayurvedic experts were of the opinion

that TKDL, besides ensuring prevention of the grant of wrong patents for

non-original inventions in our traditional knowledge system at international

level, shall also ensure enhancement of modern research in Ayurveda and provide

immense benefit to MD and PhD students, researchers and manufacturers. TKDL

will also provide a feedback mechanism on the coverage of different viewpoints

and minimize controversies on herbal drugs in future. </p>

<p>The Cabinet Committee on Economic Affairs has approved early establishment

of Traditional Knowledge Digital Library in Ayurveda in the first instance

followed by similar digital libraries in other systems of Indian medicines,

such as Unani, Siddha, Yoga, Naturopathy, etc. This was also included in the

budget speech of Hon'ble Finance Minister. </p>

<p>At international level, TKDL has received wide acceptance and support. World

Intellectual Property Organization (WIPO) in its 3^rd plenary session

at Geneva, at the initiative of India, decided to take up the creation of

traditional knowledge databases on the knowledge available in public domain so

that such databases can facilitate establishment of prior art. WIPO Standing

Committee of Information Technology (SCIT) was chaired by Dr R A Mashelkar,

Secretary, Department of Science Industrial Research and Director General,

Council of Scientific and Industrial Research. </p>

<p>WIPO's special union for the International Patent Classification (IPC)

Committee of experts in its 30^th session held at Geneva during 19-23

February 2001 decided to create a task force with United States of America,

Japan, European Patent Office, China and India as members to study in detail

the Traditional Knowledge Resource Classification (TKRC) elaborated in India

and investigate its information aspects and its relationship to IPC with a view

to linking and/or integrating TKRC with IPC. This development at international

level is extremely positive and useful to India as more than 5000

sub-classifications defined by India for Ayurveda now have the possibility to

get

integrated into IPC. This integration will ensure that every international

patent examiner shall be obliged to search for prior art on more than 5000

sub-classifications against only one sub-classification at present. Thus, this

will largely eliminate the possibilities of grant of wrong patents at

international level in the domain of our traditional knowledge system in

Ayurveda. </p>

<p>Ms Shailja Chandra, Secretary, Department of Indian System of Medicine and

Homoeopathy, has been steering the project on TKDL and has decided to get this

project implemented by National Institute of Science Communication by

constituting an dedicated interdisciplinary task force of thirty Ayurvedic

experts from CCRAS, five IT experts from NIC, five patents examiners from the

Office of CGPDTM, and fifteen scientists from NISCOM. It is expected that TKDL

in Ayurveda, will get created by March 2002 in four international languages at

a cost of Rs 10 million and will provide comprehensive coverage on more than

thirty-five thousand Ayurvedic formulations to ensure prevention of the grant

of wrong patents at international level in our traditional knowledge systems,

particularly in Ayurveda. TKDL shall also accelerate modern research in

Ayurveda leading to acceptability at international level which may have

significant impact to Indian herbal products export. It may not be out of place

to mention that India has been setting the international agenda on the

Intellectual Property aspects of Traditional Knowledge (TK) so that TK also

creates a path for wealth creation for the indigenous TK holders. <i>[Modified]

</i></p>

<p align=right style='text-align:right'><i>-- CSIR News 2001, 51(5 & amp;6),

1-3</i> & nbsp; & nbsp;

</p>

<p>-------<br>

<em><b><span style='font-size:10.0pt;font-family:Arial'>Information Today & amp;

Tomorrow, Vol. 20, No. 3, September 2001, p.16-p.17</span></b></em><b><i><span

style='font-family:Arial'><br>

<em><span style='font-family:Arial'><a

href= " http://itt.nissat.tripod.com/itt0103/tkdl.htm " ><span style='font-size:

10.0pt'>http://itt.nissat.tripod.com/itt0103/tkdl.htm</span></a></span></em></sp\

an></i></b></p>

<p> & nbsp;</p>

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[Guest guest]

Dear Dr Anupama,

Pharmacology i.e. study of drug (Pharmacon + Logos). This study is from laboratory to the clinic. Hits i.e. chemical entity or the recombinant medicines in the current era usually are tested in laboratory (in vitro) followed by in vivo studies in animals. After getting safety data and may be efficacy from different animal models, medicine is introduced into the various phases of clinical trial.

In India traditional medicine sciences like Ayurveda, Unani have long history. These preparations have known effects in the different pathological cases. The findings are being documented but in gross manner. This means that the medicines are in clinic to begin with and have safety data in hand. Reverse pharmacology starts here. This is Experiential phase of RP. From these observations the hits are isolated.

What is hit?

Hit is a molecule with confirmed activity from primary and secondary assays and with confirmed structure.

Now this hit is evaluated and transformed to lead.

What is lead?

Lead is modified series of hit molecule with known structure activity relationship (SAR) and activities demonstrated both in vitro and in vivo.

This encompasses the Exploratory phase of RP.

Once the lead is obtained the pharmaceutical procedure starts so as to get the medicine to be tested for Pk/Pd as per our regular clinical trial phases. This converts experience based knowledge into evidence based medication. This is Experimental phase of RP.

So the course of study of medicine is from clinic to laboratory and back to clinic and hence it is reverse pharmacology.

This pathway is also explained with some other terminologies in my previous post. I hope this explains the term RP.

Regards,

Smita Mali> > From: ibnsinaacademy ibnsinaacademy@...> Subject: Re: Rationale of reverse pharmacology> netrum > Date: Wednesday, 26 March, 2008, 12:16 AM> > Dear Dr. Smita Mali> > Its good to read your valuable posting on reverse pharmacology along with significant examples. Related to Rauwolfia serpentina, I would like to add that it was firstly Prof. Saleemuzzaman Siddiqui who worked on Rauwolfia serpentina during 1920s when Hakim Ajmal Khan (a renowned Unani Physician) suggested him to work on this plant roughly a decade before Sen and Bose (famous scientists of Kolkata). The alkaloid Ajmalcine (or Ajmalin) is named by Saleemuzzaman Siddiqui after the name of Hakim Ajmal Khan.. The isolation of the alkaloid was done at the Department of Chemistry of our University.> > Regards,> S. Ziaur Rahman> > > Rationale of reverse pharmacology> > > Hello NetRUMians,> > Basic pharmacology starts with various sources of medicine. Plants claim its first place in the list. Clinical uses found were serendipitous in some of the cases. In India Ayurveda, the science in itself is known and being practiced since ages. Also Unani, Homeopathy, Chinese medications are being followed in different regions worldwide.> These experiences can be used to derive hits for new medicine development. Because of the long term use being followed in community we get the assurance of safety for these new molecules and hence shortens the drug development path. Following are the examples of plant derivatives leading to the establishment of group of medicine in various treatments or discovering the target for the same.> > Medicinal plant> Clinical effect> Experimental correlate> Curare tomentosum> Paralysis and death > Neuromuscular block> Papaverum somniferum> Analgesia > Opioid receptors> Physostigma venenosum> Ordeal poison > Anticholinesterase> Cinchona officinalis> Antipyrexia > Antimalarial> Digitalis purpurea> Dropsy relief> Na+,K+-ATPase> Salix alba> Fever and pain relief > Prostaglandins> Strychnos nuxvomica> CNS stimulant > Glycinergic receptors> > > Rauwolfia serpentina Benth (Sarpagandha)> Sen and Bose not only showed the antihypertensive effects of R. serpentina, but were also astute clinicians to note certain side effects such as Parkinsonism, depression, gynecomastia, acid peptic symptoms and so on. There was almost a gap of two decades in discovering the pharmacological basis of these actions. The storage vesicles are rendered dysfunctional as a result of their interaction with reserpine and the depletion of biogenic amines explained the actions by mechanistic correlates. As a spin off of the side effects of R. serpentina, several new drugs were developed such as L-dopa, antidepressants, bromo-ergocriptine, and H 2 receptor blockers and so on. The alkaloids of R. serpentina, reserpine and ajmalcine, have served as research tools in many experiments.> Regards,> Smita Mali> > > > > > > ---------------------------------> 5, 50, 500, 5000 - Store N number of mails in your inbox. Click here. > > > > > ---------------------------------> Get the freedom to save as many mails as you wish. Click here to know how.>

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Hello,

Please find the power point presention by Ashok D.B.Vaidya, AshwinikumarA.Raut, Ashok J.Amonkar as attachment.

Reverse Pharmacology is explained nicely with examples in this.

Regards,

Dr Smita Mali

From: ibnsinaacademy <ibnsinaacademy@ gmail.com>Subject: Re: Rationale of reverse pharmacologynetrumgroups (DOT) comDate: Wednesday, 26 March, 2008, 12:16 AM

Dear Dr. Smita Mali

Its good to read your valuable posting on reverse pharmacology along with significant examples.. Related to Rauwolfia serpentina, I would like to add that it was firstly Prof. Saleemuzzaman Siddiqui who worked on Rauwolfia serpentina during 1920s when Hakim Ajmal Khan (a renowned Unani Physician) suggested him to work on this plant roughly a decade before Sen and Bose (famous scientists of Kolkata). The alkaloid Ajmalcine (or Ajmalin) is named by Saleemuzzaman Siddiqui after the name of Hakim Ajmal Khan.. The isolation of the alkaloid was done at the Department of Chemistry of our University.

Regards,

S. Ziaur Rahman

Rationale of reverse pharmacology

Hello NetRUMians,

Basic pharmacology starts with various sources of medicine. Plants claim its first place in the list. Clinical uses found were serendipitous in some of the cases. In India Ayurveda, the science in itself is known and being practiced since ages. Also Unani, Homeopathy, Chinese medications are being followed in different regions worldwide.

These experiences can be used to derive hits for new medicine development. Because of the long term use being followed in community we get the assurance of safety for these new molecules and hence shortens the drug development path. Following are the examples of plant derivatives leading to the establishment of group of medicine in various treatments or discovering the target for the same.

Medicinal plant

Clinical effect

Experimental correlate

Curare tomentosum

Paralysis and death

Neuromuscular block

Papaverum somniferum

Analgesia

Opioid receptors

Physostigma venenosum

Ordeal poison

Anticholinesterase

Cinchona officinalis

Antipyrexia

Antimalarial

Digitalis purpurea

Dropsy relief

Na+,K+-ATPase

Salix alba

Fever and pain relief

Prostaglandins

Strychnos nuxvomica

CNS stimulant

Glycinergic receptors

Rauwolfia serpentina Benth (Sarpagandha)

Sen and Bose not only showed the antihypertensive effects of R. serpentina, but were also astute clinicians to note certain side effects such as Parkinsonism, depression, gynecomastia, acid peptic symptoms and so on. There was almost a gap of two decades in discovering the pharmacological basis of these actions. The storage vesicles are rendered dysfunctional as a result of their interaction with reserpine and the depletion of biogenic amines explained the actions by mechanistic correlates. As a spin off of the side effects of R. serpentina, several new drugs were developed such as L-dopa, antidepressants, bromo-ergocriptine, and H 2 receptor blockers and so on. The alkaloids of R. serpentina, reserpine and ajmalcine, have served as research tools in many experiments.

Regards,

Smita Mali

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Hello all,

I thank Thawani sir for providing me an opportunity for moderation of topic on the NetRUM. I thank Dr Ziaur for his spontaneous addition of information on the topic.

Regards,

Dr Smita Mali

From: Dr. Smita Mali <smt_mali@...>Subject: Rationale of reverse pharmacologynetrum Date: Friday, 28 March, 2008, 3:57 PM

Hello,

Problems Confronting Indigenous Herbal Medicines

Following are problems confronted by indigenous herbal medicines:

Reluctance of the practitioners of indigenous systems of medicine to accept and assimilate modern scientific methods and tools in the pre-harvest to post-harvest processing of medicinal plants and standardized procedure for preparation of herbal formulations/ herbal drugs.

Failure to ensure consistency in batch-to-batch production of herbal drugs/formulations and consequent failure to compete at the international level

Inadequate standardization methods/tools

Lack of systematic documentation of herbal products

Rarity and danger of extinction of medicinal plant species from their natural ecosystems due to various anthropogenic activities (almost 85% of the medicinal plants required for the preparation of traditional remedies are collected from natural resources).

Reverse Pharmacology has major role to play in this regard as to overcome these problems. An integrated research approach should be followed to make the best use of traditional knowledge while using the modern tools and technology for optimal utilization of the valuable resources of medicinal plants.

This should be done by:

Sharing and networking the information or creating inventories for the traditional remedies.

Formulating policy guidelines for establishment of different parameters and procedures that best suit herbal remedies in order to fix the standards of raw drugs and finished products using pharmacognostic, chemotaxonomic molecular DNA fingerprinting and reverse pharmacology techniques, or guidelines for assessing the safety, efficacy and batch-to-batch consistency of herbal products/drugs

The manufacturing process should follow GMP compliance by being efficient, time and cost effective, with the development of in-process controls.

Regulatory issues to be followed for manufacturing units.

Registration of herbal products, viz., household remedies, herbal drugs, nutraceuticals, and traditional system remedies as separate entities.

Study the mode of action of drugs at the cellular, molecular (receptor level) and system levels, having as holistic a view as possible.

The validation of Ayurvedic and ethnobotanical claims using modern scientific methodology along with current professional practices

Availability/ cultivation of important medicinal plants and standardization of post-harvest technology

Concentration should be made on therapeutic categories, viz. development of herbal products for chronic ailments, adaptogens, immunomodulators, rheumatic disorders, degenerative diseases of old age, cancers, liver problems and diabetes, within the broad basic concepts and philosophy of Ayurveda.

Regards,

Smita Mali

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TKDL is easier said than done, a very comprehensive and important project of both CSIR and Dept of AYUSH under the command of NISCAIR. It’s a visionary idea to have such a database in India. It will not only safeguard the traditional knowledge of our yesteryears physicians but will also help in intellectual property rights in the era of present patent rules. I am little bit aware with this project as I see few of the people who are associated with this project. They are working hard to put things together after referring so many medical manuscripts and primary sources. We know only few Indian physicians who are nowadays working on primary sources. Its hard to find physicians for this project. Physicians like us are mostly working on secondary and tertiary sources. It is very difficult to read and conclude old medical manuscripts available in Sanskrit, Arabic, Persian and Pali languages. The Library of Ibn SinÄ Academy is helping some research workers who are associated with TKDL. It provides access to 300 medical manuscripts rich in medicinal contents. A brief write up about the library which is the only library from India, listed in the Directory of History of Medicine Collections, US Department of Health and Human Services, National Library of Medicine, NIH, USA can be seen through the following website: http://www.nlm.nih.gov/hmd/directory/151.html

I appreciate Dr. Smita Mali who is taking interest in such a young age about our old medical ethnicity and moderated a discussion on reverse pharmacology.

S. Ziaur Rahman

Rationale of reverse pharmacology

Hello,

Following is the abstract of review article “Ayurveda and natural products drug discovery†by Bhushan Patwardhan, Ashok D. B. Vaidya and MukundChorghade which nicely explains ayurveda, new drug discovery and place of reverse pharmacology.

This review attempts to portray the discovery and development of medicine from galenical to genomical, with a focus on the potential and role of ayurveda. Natural products, including plants, animals and minerals have been the basis of treatment of human diseases.

Indigenous people derived therapeutic materials from thousands of plants; however discovering medicines or poisons remains a vital question. Ayurveda is a traditional Indian medicinal system being practiced for thousands of years.. Considerable research on pharmacognosy, chemistry, pharmacology and clinical therapeutics has been carried out on ayurvedic medicinal plants.

Many of the major pharmaceutical corporations have renewed their strategies in favour of natural products drug discovery and it is important to follow systems biology applications to facilitate the process. Numerous drugs have entered the international pharmacopoeia through the study of ethnopharmacology and traditional medicine. For ayurveda and other traditional medicines newer guidelines of standardization, manufacture and quality control are required. Employing a unique holistic approach, ayurvedic medicines are usually customized to an individual constitution.

Traditional knowledge-driven drug development can follow a reverse pharmacology path and reduce time and cost of development. New approaches to improve and accelerate the joint drug discovery and development process are expected to take place mainly from innovation in drug target elucidation and lead structure discovery. Powerful new technologies such as automated separation techniques, high-throughput screening and combinatorial chemistry are revolutionizing drug discovery. Traditional knowledge will serve as a powerful search engine and most importantly, will greatly facilitate intentional, focused and safe natural products research to rediscover the drug discovery process.

Regards,

Smita Mali

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