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Serpentina Treatment: A Review of Literature
Serpentina Treatment: A Review of Literature
T HE plant rauwolfia is named after the patala garud or atalaganidhi (Telegu), covan-
German doctor and traveller Leonhard namiloori (Tamil), chuxvanaavilpori (Malay)
Rauwolf, who in 1582 published an and as dhannerna or dhan-barua (Oriya).
account of his many travels. Roots of the plant Of the 130 odd species of rauwolfia, which
Rauwolfia serpentina (Benith) have been are said to occur indigenously ill the tropics,
recognized in India and the _Malay peninsula Youngkeln'50 has given an excellent description
from ancient times as antidotes to the stings of the following fire, viz. R. serpentina, R.
and bites of insects and poisonous reptiles. canescens, R. micrantha, R. densiflora, and R.
Mention of the plant is found in an old Hindu perakensis. Eight species of rauwolfia grow in
manuscript (1000 B.C.)128 as well as in the India; according to origin or source of supply,
monumental works of Charaka (second cen- it is customary to recognize the Bengal,
tury, A.D.), under the Sanskrit name of Bihar, Assam, Dehra Dun and Ceylon varieties
"sarpagandha." It has also been used as a of rauwolfia in the Indian market; these show
febrifugue, as a stimulant to uterine con- considerable differences inl quality and content
tractions, for diarrhea, dysentery, insomnia of the therapeutic alkaloids. The most useful
and insanity. For just over two decades, its variety of rautwolfia from the therapeutic
clinical application has been extended with standpoint is Rt. serpentina, which grows to a
success to the treatment of high blood pres- height of one and one-half to three feet and
sure.132 has pinkish-white flowers.
R. Serpentina or the serpentina plant is a
large climbing or twininig herb or shrub, CHEMICAL COMPOSITION
belonging to the natural order Apocyanaceae, Early researches suggested the presence in
and found in the Himalayas, Assam, Pegu, the R. serpentina plant of all alkaloid, which
Java, Tennasserim, Bihar, Deccan peninsula was provisionally named psendobrucine. Since
and the Malay peninsula. It is variously known 1931, the chemical structure or composition of
as sarpagandha (from ancient times), chandrika the plant has been the subject of investigation
(Sanskrit), chota-chand (Hinidi), chand (Ben- by numerous observers.
gali), dhan-murua or dhanbarua or pagla-ka- Ill 1891, Dymock,42 for the first time,
dawa (Bihar), chandra, chota-chanid, karavi detected the presence of an alkaloid and a
or harkai (Bombay), harkaya (M\arathi), yellow resin in the root of R. serpentina.
From the Department of Cardiology, King Edward In 1931, Sen and Bosell found two alkaloids
Memorial Hospital, Bombay, Indita. in its root (the total alkaloid content being
220 Cl'rulation. Volume XII, August, 1955
about 1 per cent of the dried root), ill addition depressant to the heart, respiration and central
to fair quantities of resin and starch. Siddiqui nervous system, the serpentine group causes
and Siddi(ui"7 (1931) found, besides phytos- paralysis of respiration, depression of nerves
terol, oleic acid and unsaturated alcohols, five and stimulation of the heart. Sen and Bose"'
alkaloids with different physical characteristics (1931) reported a small drop of blood pressure,
and molecular formulae, classified by them a depression of the heart muscle, respiratory
into two groups, viz., (1) the ajmalinie group stimulation and relaxation of smooth muscles,
of three white crystalline weak bases, ajmaline in cats and other animals, after the administra-
(C26H2602N2), ajmalinine (C20H2304N\), and tion of R. serpentina alkaloids. Roy'04 (1931)
ajmalicinie; and (2) the serpentine group of two described dulling of sensations, sluggish reflexes
yellow, crystalline stronger bases, serpentine and sleep after large doses and death from
(C21H2 304N) and serpentinine (C20H20033N 2). respiratory failure after lethal doses. In 1933,
In 1932, two Dutch chemists, Van Italie Chopra and associates,24 working with the
and Stenhauerl'37 isolated three alkaloids similar total alkaloids of Rt. serpentina described
in formula or structure to the ajmalinie, valuable sedative, hypnotic and hypotensive
ajmalininie and serpentinine of Siddi(ui and properties.
Siddiquil 7-'0. They named their first alkaloid, In 1940, Haniet63 observed, for the first
rauwolfin (C21H2602N). time, the sympathicolytic activity of alkaloids,
In 1939, Siddiqui'20 reported that the only particularly, ajmaline and rauwsolfine, isolated
two alkaloids obtained from the Dehra Dun from R. serpentina (Benth), and remarked on
variety of R. serpentina differed from those of the hypotensive action of several of the
the Bihar variety in their chemical structure alkaloids.
and melting points and named them iso- In 1941 and 1942, Chopra and his asso-
ajmalinie or nieoajmalinie. In 1941, Mookheiji90 ciates26 27 reported exhaustively on the pharma-
isolated all alkaloid from R. canescens, and cological and toxic effects of R. serpentina root
named it rauwolseine (C21H2603N2). M\uller, extracts as well as of individual alkaloids; in
Schlittler and Bein,92 in 1952, isolated a new their experience, while the total alkaloids,
alkaloid, reserpin, from R. serpentina, with an alcoholic extracts and serpentine, particularly
empirical formula of C33H4009N2. In 1953, the last, possess valuable hypotensive proper-
Chowdhury and Ghosh29 isolated yet another ties, ajmaline and serpentinine are hypertensive
alkaloid, hypotensin, from the serpentine drugs. Bhatia and Kapur'2 (1944) reported,
root. after the administration in animals of the two
Other alkaloids of R. serpentina more alkaloids, isoajmaline and neoajmaline, stimu-
recently isolated and described are, sarpagine lation followed by depression of the central
(C19H2202N2), isolated and described by Stoll nervous system, and lowering of the blood
and Hofmann'23 (1953), raupine (C2oH26O):,N2), pressure in intact, spinal and decerebrate
by Bodendorf and Eder13 (1953), rauhimbine animals, with or without experimentally
(C21H1260:,N2), and iso-rauhimbine (C21H260:1N 2) induced hypertension. In 1944, Gupta, Kahali
by Hofmann167 (1954), substance I (C2 2H2604N2) and Duttt5 found that the crude resin isolated
and substance II (C21H2503N2) by Popelak and by Dymock in 1891, also possessed the sedative
associates98 (1953) and reserpinine (C22H26- and hypnotic properties of the serpentina root.
04N2) by Schlittler and associates108 (1954). Chakravarty'7 (1952) and Mukherjee9l
(1953) described the sympathicolytic effects
PHARMACOLOGIC EFFECTS of the alkaloid rauw olseine, isolated from
The pharmacologic actions of the R. R. canescens (Linn).
serpentina root and of its individual alkaloids \Iuller and associates92 (1952) and Bein8
have been investigated from time to time. (19553), on the basis of animal experiments,
Oil the basis of experiments otn frogs, found the new alkaloid reserpin to possess
Siddiqui and Siddiquil"7 (1931) showed that marked and long-lasting hypotensive, vaso-
while the ajmalinie group acts as a general depressor and sedative-hypnotic properties. In
1953, Dasgupta and associates3" described the hypertension only; the indications and sufita-
sympathicolytic activity and adrenergic block- bility of the case for the drug have not as yet
ing activity of the purified total alkaloids and been worked out."
the oleoresinous fraction of ft. serpentina. In A vague reference to the use of a tincture or
their opinion, the hypotensive action of the alcoholic extract of the root of R. serpentina,
root is only partly due to the sympathicolytic in cases of high blood pressure, was made in
effect, other factors like peripheral vasodilata- 1942 by Paranjpe.9' He claimed improvement,
tion being also concerned. Chowdhury and without ally statistical support, inl most cases
Ghosh21 (1953) reported the hypotensive effects of hypertension; the hypotensive action was
of a new alkaloid, hypotenisini, isolated from said to be particularly gratifying in elderly
the root. subjects and in the case of the diastolic
On the basis of experimnental and clinical pressure.
studies, the root of R. serpentina is said to have Ill 1942, 13hatia," after employing R. serpen-
the following pharmacologic attributes.132 tina ill the treatment of cases of high blood
(1) By action on the vasomiotor center, it pressure, both with and without renal damage,
leads to generalized vasodilatation, with a reported it as a useful and well-tolerated hypo-
lowering of blood pressure. (2) 1By depressant tensive remedy.
action oti the cerebral centers, it soothes the
general nervous system.'45 (3) It exerts a International Con'ribtutions
sedative action onl the gastric mucosa and a In 1949, ill England, Vakil'1' reported the
stimulating action on the plain musculature of results of all extensive clinical trial of the dried
the intestinal tract. (4) It stimulates the root of R. serpentina ill 50 cases of essential,
bronchial musculature. benign hypertension. Satisfactory drops of both
systolic and diastolic blood pressure levels
CLINICAL STUDIES were observed in 85 per cent and 81 per cent
Until the year 1949, in spite of many of cases, respectively, after four weeks of
notable clinical and pharmacologic contribu- therapy; it was concluded, on the basis of this
tions on the subject in India, interest in study, that ft. serpentina has "a definite place
R. serpentina therapy had remained strictly ill the treatment of high blood pressure."
localized to that country. The following are among the most note-
When, in 1949, the author'32 published in worthy of the international contributions onl the
England the first clinical report on ft. serpentina subj ect.
therapy to appear outside of India, interest in From the United Stales. Ill 1953, after
the subject soon became international. Since carrying out clinical trials in over 100 cases,
that time, contributions, both clinical and over periods varying from one month to one
pharmacologic, o1n the subject of f. serpen- year, Wilkins and Judson,'48 found R. serpen-
tina, have been literally pouring forth from tina useful in lowering high blood pressure
different countries of the world. levels, nonihabit forming, free of serious side
effects, and applicable in most cases of hyper-
Earlier Indian Contributions tension. In the opinion of Wilkins,1461-49 R.
Although the therapeutic value of R. serpentina is "a valuable addition to our armna-
serpentina in cases of insanity, particularly mentarium against hypertension," possessing
when associated with maniacal tendencies, was both symptom-reliev inig and hypotensive
recognized in 1931 by Sen and Bosell' and properties, especially ill young labile hyper-
subsequently confirmed by Ghosh in 1940, the tensives with sensitive nervous systems.
first mention in the literature of its value in Amongst side effects, he observed nasal
human cases of hypertension was in 1940, stuffiness, a tendency to diarrhea, gain ill body
when Vakil'30 made the following allusion to weight, nightmares and, on rare occasions, a
the subject: "After a trial of this preparation, sense of "depressed anxiety" or jitteriness.
one finds it useful in a percentage of cases of Optimal results were obtained with a dose of
cerebral arteriosclerosis. Jxlausgraber74 (1953), hypertension, and without ill effects. In 195:3
in Vienna, tried the drug in 8.3 cases of hyper- Vakil'33 reported a good hypotensive response
tension of diverse types; some cases were to the alkaloid reserpine in 72 per cent of
associated with renal an(l cardiovascular cases, and few side effects. The accidental ad-
complications. A satisfactory response of both ministration of 10 times the therapeutic dose
systolic and diastolic pressures was obtained in to one patient merely resulted in a transitory
6:3 per cent of cases. Although all cases were feeling of lassitude and vertigo.
subjectively improved, the electrocardiographic Manay more studies, hitherto unpublished,
tracings, retinal fields, renal function tests and on the hypotenisive action of R. serpentina
teleradiograms remained unaffected by the root or of its individual alkaloids, either used
treatment . singly or in combination with hypotensive
From Switzerland. In 1'953 Loffler and agents like veratrum viride, hexaimethoniiun
associates83 tried the alkaloid reserpin, isolated and hydralazine, have been brought to light,
from R. serpentina by Swiss workers, in 51 recently, from various parts of the universe.
cases of hypertension. Adequate falls of The results are said to be uniformly good in
pressure were observed in only 14 cases and mild and moderate cases of hypertension and
maintained for only 12 days in spite of con- devoid of any serious or toxic ill effects. As far
tinuationi of therapy. Subjec tive improvement as can be ascertained, the results obtained with
was reported in 16 cases, and side effects, individual alkaloids of R. serpen/ina have not
including fatigue, depression, excitability, pain- differed materially from those obtained with
ful extremities, visual phenomena, miosis and the (rude extracts of the root.
dryness of mucous membranes only inl cases
treated with doses larger than 1.5 mng. per day. PRESENT DAY 'iSTATUS OF
From Japan. In 1954 (oto22 found the R. Serpentina THERAPY
alkaloid reserpin effective in 12 out of 13 cases Il the short span of about 15 years that the
of hypertension. The hypotensive action was dried root of R. serpentina has beeni on the
apparent three to seveni days after initiation of market in India, this hypotensive remedy has
therapy and maintained for t0 to 21 (lays after gaiiled such unprecedented popularity that
its suspension. Nose block and "pharyngeal the following statements canl be made: (1)
bolus" were observed in three cases. Oii trying There is hardly one patient with high blood
various combinations of R. serpentirna with pressure in that country who has not been
veratrum viride and Apresoline in 72 cases of subjected at some time or another to its
hypertension, including 18 cases of renal application'32. (2) In the experience of ovem 90
hypertension, Goto obtained a hypotenisive per (cet of Indian doctors, as revealed by a
response of 30 mm. or over within a month of (luestiomiaire circulated by Vakil in 1949,132
the initiation of therapy in 83 per cetit of cases; R. serpentina is the best "hypotensive" remedy
this result was maintained for two to four knownm. (3) One manufacturing firm alone
months. Apart from o(ccasionial -vertigo and claims to hare sold, prior to the year 1954,
conjunctivitis, there were io side-rea(ctionls. over 98 million tablets of the dried root, of
From India. In 1952, (1hakravarty and R?. serpentina.'6 (4) Shipments of the serpentina
associates17 reported average systolic and root in crude or tablet form have been sent
diastolic pressure falls of 18.5 mm., and 16.4 from India to over 17 countries of the world
mIm., respectively, on the tenth day of R. within the last four years.'6 (5) It is said to be
serpentina therapy. Mazimidar and \Iukher- prescribed by over 60,000 physicians at the
jee86 (1951) reported subjective improvemeint present time. ' 6
in all cases and a hypotensive response in 7
out of 12 cases of hypertension. Chowdhury R. Serpentina: Crude Extracts TVersus. Pure
and Ghosh29 (1953), found the alkaloid "hypo- A l1;aloids
tensin ", isolated from R. serpentina inl Calcutta, For many years now, and particularly after
effective, even in small doses, in most cases of the isolation of the alkaloid, reserpinie, a strong
Circulation. 1955;12:220-229
doi: 10.1161/01.CIR.12.2.220
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX
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Copyright © 1955 American Heart Association, Inc. All rights reserved.
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