Ancient Science of Life, Vol. 30, No.
3 (2011) Pages 78 - 83
Sedative Hypnotic Activity of Manahshila (Realgar) - An Experimental Evaluation
* 1 2 3
Naveena Kodlady , M. S. Doddamani , Y. Vishwanath , B. J. Patgiri
1
Department of Rasashastra & Bhaishajya Kalpana including Drug Research, IPGT & RA, Gujarat Ayurved University,
Jamnagar- 361008, Gujarat, India.
2
PG Department of Rasashastra, Taranath Govt. Ayurvedic Medical College, Bellary, Karnataka, India.
3
Department of Pharmacology, Vijayanagara Institute of Medical Sciences, Bellary, Karnataka, India.
ABSTRACT
Manahshila (Realgar) is one of the three major Arsenicals
used in Ayurvedic therapeutics since ages. It is indicated in
skin, respiratory, ophthalmic and psychological disorders. It
is mentioned to be the best among Rasayanas and a good
aphrodisiac. As Manahshila is indicated in Unmada
(Psychological disorder); wide use of Manahshila in the
formulations mentioned for psychological disorders; some
of those formulations are used in treatment of sleeplessness
and Ardraka (Zingiber officinale Roscoe.) which is a
commonly used Shodhana (purification) reagent of
Manahshila is reported to be sedative, the potential sedative
hypnotic activity is inferred and an experimental study was
carried out to evaluate the sedative hypnotic activity of
Manahshila. Effect of Ardraka Shodhita Manahshila (ASM)
on the spontaneous motor activity of albino rats in
actophotometer and on diazepam induced sleeping time was
evaluated. There was a statistically significant reduction in
the spontaneous motor activity (P<0.001) in ASM treated
albino rats. An early onset of sleep and hypnotic
potentiation of Diazepam induced sleep was also found with
ASM treated rats in another experiment (p<0.01).
Key words: Sedative hypnotic, Spontaneous Motor Activity,
Actophotometer, Sleeping Time Test, Psychological
Disorders.
Introduction:
Arsenic has been used as a therapeutic agent throughout the
globe since centuries.1 Manahshila (Realgar) is one of the
Arsenic compounds, which has been advised in therapeutics
in ancient texts of Ayurveda, Charaka Samhita (eg.
Manahshiladi Lepa 2 for external application and
Manahshiladi Ghrita3 for internal administration) and
Sushruta Samhita (eg. Manahshiladi dhooma varti4for
inhalation of smoke after ignition and Manahshiladyanjana5
for application to eye). Later with the evolution of
specialized branch of Indian alchemy - Rasashastra -,
Manahshila has been extensively used in various
formulations for internal as well as external administrations.
Ayurveda uses three major Arsenicals viz. Manahshila
(Arsenic Disulphide or Realgar or Red Arsenic), Haratala
(Arsenic Trisulphide or Orpiment) and Gouripashana
(Arsenic Trioxide or Arsenolite or White Arsenic), only after
proper detoxification by following specified Ayurvedic
Shodhana (Purification). Manahshila is a red coloured,
shiny arsenical available naturally. Pieces of Manahshila are
of different shapes with red, yellow or blackish spots on its
surface. But when powdered it looks orange coloured.6
* Corresponding author
78
1
Global traditional medical use of realgar includes
malignancies, skin diseases, sedatives antipyretic, anti-
inflammation and ulcers.1 In India since ancient times
Manahshila is being mainly used in skin diseases,
respiratory diseases and eye diseases. Other indications
include Visha (Poisonings), Kshaya (Emaciation), Jvara
(Fever), Agnimandya (Loss of appetite), Apasmara
(Epilepsy), Bhootavesha Bhaya (Fear of ill effects of evil
forces) and Chardi (Vomitting). It is said to be Vrushya
(Aphrodisiac) and best among the Rasayanas
(Rejuvenator).7, 8
Reference of indication of Manahshila in Unmada is found
in Raja Nighantu which is a lexicon of 15th century A.D and
it terms Manahshila as Vashyakarini (Hypnotic). 9
Manahshila has been used in many formulations prescribed
in Manasa rogas (psychological disorders) like Unmada
Gajakesari Rasa,10 Bhootankusha Rasa,11 Bhootabhanjini
Vati10 and Vata kulantaka rasa12 etc. Its formulations like
Unmadagajakesari Rasa and Smrutisagara Rasa have
practical indications on Anidrata (Insomnia) too.13
Unpurified Manahshila is a poisonous substance which on
administration causes hazardous effects on the body like
Mandagni (Decreased digestive power), Ashmari(Renal
calculi), Malavishtambhakari (Constipation), Mutrkricchra
(Painful Micturation), Sharkara (Gravel), Mutradaha
(Burning micturation) and Mutrarodha (Obstructed
micturation).14 Hence purification of Manahshila is the
primary requisite before its medicinal usage. There are more
than 15 Shodhana reagents mentioned for the purification
process among which Ardraka Swarasa Bhavana
(levigation with ginger juice) for seven times15 is used in this
study and is commonly observed in majority of Rasashastra
classics.
Ardraka (Zingiber officinale Roscoe) contains aromatic
principles like zingiberene and bisabolene and the pungent
principles like gingerols and shogaols. In laboratory
animals, the gingerols increase the motility of the
gastrointestinal tract and have analgesic, sedative,
antipyretic and antibacterial properties.16-18 Ardraka
Shodhita Manahshila (ASM) is reported to be safe19 and
ginger is in the list of GRAS (Generally Rated As Safe)
document of US FDA20
Sedative is a drug that subdues excitement and calms the
subject without inducing sleep, though drowsiness may be
produced. Hypnotic is a drug that induces sleep and /or
maintains sleep. Sedative hypnotics are more or less general
CNS depressants with somewhat differing in time action and
dose action relationship.21
Considering the potential use of Manahshila in
psychological disorders and insomnia, the claimed
 ANCIENT SCIENCE OF LIFE
action of its Shodhana reagent Ardraka is found to be a
sedative, an experimental evaluation of sedative hypnotic
activity of ASM was carried out by studying spontaneous
motor activity (SMA) in albino rats using actophotometer
and by diazepam induced sleeping time test (Hypnotic
Potentiation Test) in albino rats.
Materials and methods
Preparation of Trial Drug
Before the preparation, raw materials were collected from
local market and confirmed for their authenticity based on
Ayurvedic descriptions of acceptable Manashila, 6
compositional chemical analysis for Arsenic and Sulphur,
and XRD (X-Ray Diffraction) study. Shodhana of
Manahshila was done by Bhavana (Levigation) with
Ardraka Swarasa for seven times. Total of 660ml of Ardraka
swarasa was digested in 250g of Manahshila.
Animal Studies
Healthy Wistar albino rats of either sex weighing 150-200g
were selected and used for the study. They were housed at 25
30C with constant humidity 40 - 60%, on a 12 h natural day
and night cycles. They were provided standard food pellets
green leafy vegetables and water ad libitum. Experiments
were conducted with the approval from the Institutional
Animal Ethics Committee (VIMS/IAEC/05/2006-07) and
were conducted as per the CPCSEA (Committee for the
Purpose of Control and Supervisions on Experimentations
on Animals) guidelines.
1. Study of Spontaneous Motor Activity using
Actophotometer
The study of spontaneous motor activity of rats using
Table No.1: Shows drugs according to groups in Experiment No.1
Group Number of Rats Drug
NC 6 2% Gum acacia
ASM 6 ASM
RS 6 Diazepam
Procedure:
Actophotometer was switched on.The rat was placed inside
gently and the activity cage was closed with upper closing
plate. Basal activity score of each rat for 10 min was taken
separately. Specific drugs were administered to the
respective groups orally. Scores were recorded for 10 min at
the intervals of 30 min, 60min, 90 min and 120min after the
drug administration.
Statistical analysis:
The results were analyzed by using one - way ANOVA
followed by Dunnet Multiple t Test (DMTT) using
Sigmastat software, Version 3. Results were presented as
Mean Standard Error of Mean (SEM). The percent
reduction in motor activity was also calculated, by the
following formula: % reduction in motor activity = [(A-
B)/A] 100, where A = basal score, B = score after drug
treatment.
Ancient Science of Life, Vol. 30, No.3 (2011) Pages 78-83
79
Actophotometer22, 23 is employed to evaluate the action of the
drug on CNS. The sedative hypnotic drug causes decreased
SMA due to the CNS depressant action of the drug.
Fixation of Rat Dose
Human dose of Manahshila is 1/24 - 1/16 Ratti 24 (5.2-
7.8mg). As higher dose is recommended by contemporary
Rasa experts25, maximum dose has been considered for the
experimental purpose. This was converted into animal dose
based on Paget and Barne's surface area ratio which works
out to be 0.7mg /kg body weight.
i.e. Rat dose / kg body wt. = 0.018 x Human dose x 5
= 0.018 x 7.8mg x 5
= 0.7 mg / kg body weight.
Similarly, recommended daily human dose of diazepam for
sedative hypnotic purpose is 5-10mgTID-QID26 and the
maximum dose 40mg/kg body weight was considered and
rat dose of diazepam was calculated accordingly and it
becomes 3.6 mg/kg body wt. Standard dose (SD) was given
to control group. Suspension of Manahshila was prepared
with 2% gum acasia solution and solution of diazepam was
prepared with distilled water.
Grouping:
In the present study, 18 albino rats of either sex were
randomly grouped into three groups of six each. One served
as normal control (NC) and received 2% gum acacia
suspension, the second group as trial that received ASM, the
drug under evaluation and third group served as reference
standard (RS) that received the drug diazepam.
Purpose Dose
To serve as control 5ml / kg body wt
To serve as trial 0.7 mg/kg body wt
To serve as standard 3.6 mg/kg body wt
2. Diazepam Induced Sleeping Time Test
27,28
In the diazepam induced sleeping time test , two groups of
6 animals each were taken. One as control group receiving
2%gum gum acasia suspension and other trial group
receiving ASM. They were administered orally with their
respective doses just as in Exp.No.1. After one hr of
administration of respective drugs, both the groups were
administered with diazepam (25mg/kg body weight)
intraperitoneally. Rats were observed for loss of righting
reflex (normal posture of the rat) and it was considered as the
sign of onset of sleep. The interval between loss and
recovery of righting reflex was used as the index of hypnotic
effect. Early onset and/or prolonged sleep compared to
control group indicates the potential sedative hypnotic
activity in the test drug. Resulted were analyzed with
Student's t test (unpaired).
 Sedative Hypnotic Activity of Manahshila (Realgar) - An Experimental Evaluation
80

Observations & Results:

Table No 2: Shows effect of Spontaneous Motor Activity on albino rats

Activity Score
Group Dose
(mg/kg)
0 min 30 min 60 min 90 min 120 min
387.167 357.667 237.167 240.833 296.500
NC SD
10.965 10.701 6.685 5.313 6.443
385.500 205.500 177.667 170.000 178.000
ASM 0.7
12.712 13.921 11.913 5.538 4.705
371.000 172.167 99.833 81.667 62.167
RS 3.6
16.375 9.803 6.1408 6.712 5.991
F 0.431 72.546 63.437 183.523 413.755

P >0.05 <0.001 <0.001 <0.001 <0.001

Data: Mean SEM; n=6 in each group; One way ANOVA.

Table No. 3: Shows reduction in Spontaneous Motor Activity in albino rats

Reduction in Activity Score
Group
30min 60min 90min 120min
NC 29.50 7.39 150.000 10.247 146.333 13.757 90.667 15.825
ASM 180.00 09.96* 207.833 12.012* 215.500 11.566* 207.500 13.017*
RS 198.83 24.77* 271.167 21.902* 289.333 22.128* 308.833 20.934*
F 33.668 15.115 18.879 41.670
P <0.001 <0.001 <0.001 <0.001

Data: Mean SEM, n=6 in each group, One way ANOVA; DMTT *P<0.05; ASM and RS Vs Control

Effect of Spontaneous Motor Activity on albino rats is shown in the Table No. 2 and reduction (actual change) in Spontaneous
Motor Activity in albino rats is shown in the Table No.3. At the interval of 30 min of administration of ASM, it shows significant
sedative hypnotic effect compared to control group (P<0.05). After 60 min of administration of ASM, it shows significant
sedative hypnotic effect compared to both standard and control groups, which is statistically significant (P < 0.05). After 90 min
of administration of ASM, it shows good sedative hypnotic effect compared to both standard and control groups, which is
statistically significant (P < 0.05). After 120 min of administration of ASM, there is significant Sedative hypnotic effect at (P<
0.05) when compared to control group.

Table No. 4: Percentage Reduction in Spontaneous Motor Activity in different groups at different time intervals.

Group % Reduction in SMA

30 min 60 min 90 min 120 min
NC 7.62% 38.74% 37.80% 23.42%
ASM 46.69% 53.91% 55.90% 53.82%
RS 53.59% 73.08% 77.99% 83.24%

Percentage reduction in Spontaneous Motor Activity in different groups at different time intervals is shown in the Table No.
4 and is represented in the Graph No. 1. In comparison with control group, after 30 min of drug administration, additional
39.07% of reduction in spontaneous motor activity was found by ASM while additional 45.97% reduction of spontaneous
motor activity was found by diazepam. After 60 min of drug administration, additional 15.17% of reduction in spontaneous
motor activity was found by ASM while additional 34.34% by diazepam. After 90 min of drug administration, additional
18.1% reduction in spontaneous motor activity was found by ASM while additional 40.19% by diazepam. After 120 min of
drug administration, additional 30.4% of reduction in spontaneous motor activity was found by ASM while additional 59.82%
by diazepam.

Ancient Science of Life, Vol. 30, No.3 (2011) Pages 78-83

 ANCIENT SCIENCE OF LIFE 81

Chart.No.1:Shows % reduction in Spontaneous Motor Activity in different groups

at different time intervals in Exp.No.1

% Reduction in SMA

Experimental Mean Time (min)

In experimental study, statistically significant sedative hypnotic effect was seen at intervals of 30, 60 and 90 and 120 min after
drug administration, observed by studying the spontaneous motor activity of rats using actophotometer (P<0.001)

Table No 5: Shows effect of ASM on diazepam induced sleep in rats:

Dose Dose of Diazepam Latency of onset of sleep

Group Duration of sleep (min)
(mg/kg) (mg/kg) (min)
NC SD 25 08.50 00.85 270.30 07.04

ASM 0.7 25 05.50 00.34* 283.70 09.12

Data : Mean SEM

*P < 0.01, Student's t test (Unpaired)

Modern pharmacological evaluations reveal that both Sheeta

Discussion
Results suggest that the hypothesis that Manahshila has
sedative hypnotic activity is true. The study supports the basis
for the use of Manahshila in the formulations intended to treat
psychological diseases and insomnia. It also supports logic
that Nidrajanana (Sedative hypnotic) drugs are one of
choices of medications in the management of psychological
disorders.29 Manahshila is basically a Vata Kaphahara
(Pacifier of Vata and Kapha) drug possessing qualities like
Snigdha (Unctous), Guru (Heavy), Ushna (Hot) and Sara
(Mobile). Because of these qualities it can subside Vata.
Anidrata (Insomnia) is a condition caused predominantly due
to Vata Prakopa. Vata is main controller of mind. When Vata
is with its proper movement, there will be Chittaprasadana
(Nourishment of mind) by which the normal sleep is
enhanced. Hence by maintaining the normalcy of Vata,
Manahshila is becoming a sedative hypnotic. The process of
this action is triggered by its Shodhana reagent which is
Vatahara in nature. Ardraka which is Vatahara (Vata
pacifier) and Madhura Vipaka(Sweet post-digestion taste)
would add to sedative hypnotic activity.
Veerya (Hot potency) as well as Ushna Veerya (Cold
Potency) drugs can possess sedative activity. Jatamamsi
(Nardostachys jatamansi)30, Jatiphala (Myristica fragrans)31
are examples to the prior while Vacha (Acorus calamus)32,
Kupilu (Strychnos nux-vomica) 33 and Sarpagandha
(Rauwolfia serpentina)34 examples to the latter category.
Madya (Alcohol), known sedative hypnotic used since ages
that is categorized under Madakari (Drugs altering
sensorium) 35 group also an example of Ushna veerya (Hot
Potency) drug to possess this action.
Sedative hypnotics act by potentiating the inhibitory
neurotransmitter of the brain GABA (Gamma-Amino
Butyric acid).36 Increasing the activity of the GABA
neurotransmitter causes a relaxing effect by slowing down
the activity of the brain. The Arsenic trioxide is reported to be
passing blood brain barrier.37 Manahshila that is also an
Arsenic compound could also pass blood brain barrier and
potentiate the inhibitory neurotransmitter GABA to cause
sedative hypnotic effect. However exact mechanism of
sedative hypnotic activity of Ayurvedically purified
Manahshila is not yet explored and remains a thrust area of
research.

Ancient Science of Life, Vol. 30, No.3 (2011) Pages 78-83

 Sedative Hypnotic Activity of Manahshila (Realgar) - An Experimental Evaluation
Conclusion
Ardraka Shodhita Manahshila possesses sedative hypnotic
activity confirmed through animal experimental models
particularly by reduction of spontaneous motor activity
assessed through actophotometer method and potentiating
the diazepam induced sleeping time.
Acknowledgements
Authors express their sincere gratitude to Dr. B.
Ravishankar, Director, SDM Centre for Research in
Ayurveda and Allied Sciences, Udupi for guiding animal
experimental methods, Prof. Srinivas V, Head, Dept. of
Pharmacology, VIMS, Bellary, Prof P K Prajapati and Dr.
Galib, Dept of Rasashastra and Bhaishajya Kalpana; Dr
Ashok B K, Pharmacology Laboratory, IPGT&RA, GAU,
Jamnagar for their technical inputs and encouragement for
this work.
References
1. Jie Liu, Yuanfu Lu, Qin Wu, Robert A. Goyer, and Michael
P. Walkers. Mineral Arsenicals in Traditional Medicines:
Orpiment, Realgar, and Arsenolite. J Pharmacol Exp Ther
2008;326:363-8.
2. Vaidya Yadavji Trikamji. Agnivesha's Charaka Samhita.
Varanasi: Krishnadasa Academy; 2000 Chikitsa sthana , 7/
167, p. 458.
3. Vaidya Yadavji Trikamji. Agnivesha's Charaka Samhita.
Varanasi: Krishnadasa Academy; 2000. Chikitsa sthana
17/145-146, p. 543.
4. Vaidya Yadavji Trikamji. Sushruta's Sushruta Samhita. 7th
ed. Varanasi: Chowkambha Orientalia; 2002. Uttraratantra,
51/49-50, p. 764.
5. Vaidya Yadavji Trikamji. Sushruta's Sushruta Samhita. 7th
ed. Varanasi: Chowkambha Orientalia; 2002 Uttaratantra,
51/14, p. 642.
6. Jha CB.. Ayurvediya Rasashastra. Varanasi: Chowkambha
Surabharati Prakashna; 2000. p. 263-4.
7. Dattatreya Anata Kulkarni. Vagbhatacharya's Rasa Ratna
Samucchaya. New Delhi: Meharachanda Lacchamanadas
Publications; 2006. 3/91, p. 57.
8. Kashinatha Shastri. Sadananda Sharma's Rasa Tarangini.
11th Ed. New Delhi: Motilala Banarasidas; 1979. 11/116, p.
262.
9. Indradev Tripathi. Pandit Narahari's Raja Nighantu. 3rd ed.
Varanasi: Chowkambha Krishnadas Academy; 2003. p.
438 .
10. Kaviraja Shri Ambika Datta Shastri. Govindadas's
Bhaishajya Ratnavali. 18th ed. Varanasi: Chowkambha
Sanskrit Samstana; 2005. 24/35-37 and 31-33, p. 514 .
11. Kaviraja Shri Ambika Datta Shastri. Govindadas's
Bhaishajya Ratnavali. 18th ed. Varanasi: Chowkambha
Sanskrit Samstana; 2005. 24/46-51,p. 515.
12. Kaviraja Shri Ambika Datta Shastri. Govindadas's
Bhaishajya Ratnavali. 18th ed. Varanasi: Chowkambha
Sanskrit Samstana; 2005. 25/26 -29, p. 523.
13. Vaidya Ram Raksha Patak. Ayurveda Sara Sangraha. 21st
ed. Nagpur: Shri. Bhadyanath Ayurveda Bhavan Pvt. Ltd;
2004. p. 410.
14. Kashinatha Shastri. Sadananda Sharma's Rasa Tarangini.
11th ed. New Delhi: Motilala Banarasidas; 1979. 11/107-
108, p. 260.
Ancient Science of Life, Vol. 30, No.3 (2011) Pages 78-83
82
15. Dattatreya Anata Kulkarni. Vagbhatacharya's Rasa
Ratna Samucchaya. New Delhi: Meharachanda
Lacchamanadas Publications; 2006. 3/92, p. 58.
16. Mascolo N, Jain R, Jain SC, Cappasso F.
E t h n o p h a r m a c o l o g i c a l e ff e c t o f G i n g e r. J
Ethnopharmacol 1989;27:129-40.
17. Mary Ann O'Hara, David Kiefer, Kim Farrell, Kathi
Kemper. A Review of 12 Commonly Used Medicinal
Herbs. JAMA& Archieves, Arch Fam Med. 1998;7:523-
36.
18. Bhattacharjee S K. Handbook of Aromatic Plants. Jaipur:
Pointer Publishers; 2004. p. 473-4.
19. Dr. M. Krithiga. Dr. R.S.Sarashetti, Dr. M. Karigaudar,
Dr.Abdul Sattar. Physico chemical analysis and toxicity
study of Shuddha Manashila prepared with various
swarasas. MD thesis. Bangalore: Rajeev Gandhi
University of Health Sciences; 2008.
20. Anonymous, ICMR Bulletin, Ginger - Its role in
xenobiotic metabolism. New Delhi: Govt. of India,
2003;33:59.
21. TripatiKD. Essentials of Medical Pharmacology. 5th ed.
New Delhi: Jaypee Brothers Medical Publishers(P)Ltd;
2003. p. 400.
22. Pillai KK. Experimental Pharmacology. 1st ed. New
Delhi: CBS publisher; 1999. p. 85.
23. Kulkarni SK. Hand Book of Experimental
rd
Pharmacology. 3 ed. New Delhi: Vallabha Prakashana;
1999. p. 117.
24. Kashinatha Shastri, Sadananda Sharma's Rasa
Tarangini. 11th ed, New Delhi: Motilala Banarasidas;
1979. p. 263.
25. Siddinandan Mishra. Ayurvedeeya Rasashastra. 14th ed.
Varanasi: Chowkambha Orientalia; 2004. p. 454.
26. Louis Sanford Goodman, Alfred Gilman . The
Pharmacological Basis of therapeutics. Laurance L.
Brunton (ed), 11th ed. New Delhi: McGraw Hill
Publishing Division; 2006. p. 410.
27. Kulkarni SK. Hand Book of Experimental
Pharmacology. 3rd ed. New Delhi: Vallabha Prakashana;
1999. p. 115.
28. Ravishankar B., C.K.Sasikala. Pharmacological
Evaluation of Compound Ayurvedic preparations Part -
C: Vettimaran Gutika (VTG). Ancient Science of Life
1983; 3:11-18.
29. Shasthri JLN. Dravyaguna Vignana. 1st Vol, 1st ed.
Varanasi: Chaukambha Publications; 2007. p. 239.
30. Arora RB, Arora CK. Hypotensive and tranquillizing
activity of jatamansone (valeranone). In Pharmacology
of Oriental Plants. Chen KK, Mukerji B. editors.
London: Pergamon Press Ltd. 1965. p. 51-60.
31. Grover JK, Khandkar S, Vats V, Dhunnoo Y, Das D.
Pharmacological studies on Myristica fragrans -
Antidiarrheal, hypnotic, analgesic and hemodynamic
(blood pressure) parameters. Exp Clin Pharmcol
2002;24:675.
32. Mukherjee Pulok Kumar, Kumar Venkatesan, Mal
Maina, Houghton Peter. Acorus calamus.: Scientific
Validation of Ayurvedic Tradition from Natural
Resources. Pharm Biol 2007;45:651-56.
33. Katiyar C, Kumar A, Bhattacharya SK, Singh RS.
Ayurvedic processed seeds of nux-vomica:
Neuropharmacological and chemical evaluation.
Fitoterapia 2010;81:190-95.
 ANCIENT SCIENCE OF LIFE 83

34. Niaz Ahmed Khan, A. Z. M. Manzoor Rashid. A study on

the Indigenous medicinal plants and healing practices in
Chittagong hill tracts (Bangladesh). Afr J Tradit
Complement Altern Med 2006;3:37-47.
35. Vi d y a s a g a r a P a n d i t a P a r a s h u r a m a S h a s t r i .
Sharangadhara's Sharangadhara Samhita. Varanasi:
Chowkambha Surabharathi Prakashana; 2006. p. 39.
36. Remington, The Science and Practice of Pharmacy, 21st ed.
Philadelphia: Lippincott Williams & Wilkins; 2005. p.
1487.
37. Annnet Helwig Matthias Klemmb, Reinhard Schttig,
Christoph Rllig, Nasstasja Wassilew, Gerhard Ehninger,
et al, Arsenic induced APL (Acute Polumyelocytic
leucamea) differentiation in Cerebrospinal fluid, Leuk Res
2007;31:703-5.

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