Use of rauwolfia serpentina benth. in neuropsychiatric conditions

The root of the Rauwolfia serpentina Benth (N. O. Apocyanaciae) has been in use in India for hundreds of years for a host of unrelated ailments. Since 1949, after the English publication of a clinical report by the author on Rauwolfia serpentina therapy in fifty cases of essential hypertension, the plant has gained universal acclamation as a useful therapeutic weapon in high blood pressure states. The whole subject of Rauwolfia serpentina therapy in hypertension has been reviewed up to the present time, including discussions on the history of the plant, its various species and types, nomenclature, geographic distribution, chemistry, pharmacologic actions and clinical studies, reported on the subject from all over the world.

Rauwolfia Serpentina in the Treatment of High Blood Pressure A Review of the Literature

Rauwolfia is an important genus of the plant family Apocynaceae. There are nearly one hundred and twenty‐five species of Rauwolfia which are distributed all over the tropical regions of the world (1‐8). The most important member of the genus is R. serpentina Benth; the crude drug was known to the ancient Indians as a useful febrifuge (8), a remedy for snake bite, and as a cure for dysentery. In more recent times it has been used for insomnia, hypochondria and insanity.

The presence of alkaloidal principles in R. serpentina was first pointed out in 1890 by Greshoff (9). In 1933, Chopra, Gupta, and Mukherjee (10) reported the hypotensive activity of the material extracted from the plant and in 1931 Siddiqui and Siddiqui (11) isolated a series of crystalline alkaloids from R. serpentina. Active chemical and pharmacological interest in R. serpentina has resulted in the discovery of several new alkaloids (Table I). The isolation by Muller, Schlittler, and Bein (12) of reserpine, an alkaloid with pronounced hypotensive and sedative activity, has lent further impetus to the pharmacological and chemical study of the alkaloids of R. serpentha. A brief summary of the chemical aspects of R. serpentina will be presented in this review.

The alkaloids of Rauwolfia serpentina benth

This small shrub, native to the Orient from India to Sumatra, has for centuries been used in Indian medicine. In 1952 reserpine, one of several alkaloids in the plant, was isolated from its root and has since been evaluated in western medicine as one of the most valuable druǵs for treatinǵ hiǵh blood pressure.

Rauvolfia serpentina—Its history, botany and medical use

Es wird die Isolierung von zwei neuen Alkaloiden aus Rauwolfia serpentina Benth. beschrieben. Die Bruttoformel C21H26O3N2 sowie physikalische und chemische Eigenschaften kennzeichnen sie als Isomere des Yohimbins, was durch die Bezeichnung Rauhimbin und Isorauhimbin zum Ausdruck gebracht wird.

Rauhimbin und Isorauhimbin, zwei neue Alkaloide aus Rauwolfia serpentina Benth. 2. Mitteilung über Rauwolfia‐Alkaloide

yon 2 t0 -4 m lest. Die gleichen Ergebnisse h a b e n vor uns TIVOli, SON ~) m i t e inem unge re in ig t en Gehi rnchol ines te rase p r~pa ra t uud MASSART n n d DU~AIT n) m i t der Se rumchol in es te rase e rha l ten . Zur K l g r u n g dieser ~Widersprfiche wurde dahe r eine eingehende U n t e r s u c h u n g der A r s e n i t h e m m u n g unse r e r A C h E anges te l l t . W i t f a n d e n dabei , dab du rch Z usa t z von Arsen i t v611ig verg i f te te F e r m e n t a n s g t z e s ich bere i t s d u t c h 24stf indige Dia lvse gegen dest i l l ier tes W a s s e r volls tXndig reak t iv ie ren lieBen, was gegen eine feste M e r c a p t i d b i n d u n g spr ichL Bei V e r w e n d u n g einer o rgan i schen dre iwer t igen Arsenv e r b i n d u n g ( m a m i n o p h y d r o x y p h e n y l a r s e n o x y d , Maphar sen) sind, u m eine gleich grof3e H e m m u n g zu erreichen, wie sic d u t c h Arseni t erfolgt, u m zwei Z e h n e r p o t e n z e n h6here molare K o n z e n t r a t i o n e n erforderl ich, obwohl n a c h der LiteraturI2), ~) das Gegente i l zu e rwar ten w~Lre. V e r w a n d t e n wi t an Stelle yon N a t r i n m a r s e n i t die ana logen V e r b i n d u n g e n der Metal io ide Selen u n d Tel lur (Na t r iumseleni t u n d Na t r iumte l lu r i t ) , welche gleihhfalls Mercap t id b i ldner sindl~), so blieb die H e m m u n g der A C h S p a l t u n g se lbs t hei V e r w e n d u n g yon K o n z e n t r a t i o n e n in der Gr6Be t 10 2 m aus. Die H e m m u n g der A C h E du rch N a t r i u m a r s e n i t sche in t dahe r n i ch t au f d e m Wege der M ercap t i db i l dung mi t einer fiir die F e r m e n t a k t i v i t g t wich t igen S I t G r u p p e z u s t a n d e zu k o m m e n . Wie die Io lgenden Versuche zeigen, liegt der A n g r i f f s p u n k t des Arsen i t s o f fenbar a m , , ak t iven Z e n t r u m \" der ACHE. Bei gleicher Arsen i t u n d versch iedener S u b s t r a t k o n z e n t r a t ion wird die S p a l t u n g des ACh u m so m e h r gehemms je kleiner die zugese tz t en ACh-Mengen sind. E s hande l t sich d e m n a c h u m eiue k o m p e t i t i v e H e m m u n g , w o m i t wahr sche in lictl g e m a c h t wird, dab Arsen i t u n d ACh an der gleichen akr iven Gruppe des F e r m e n t e s angre i fen . E inen we i t e r en Beweis hierft ir l iefer ten Ver suche m i t e inem H e m m s t o f f au s der Re ihe der A l k y l p h o s p h a t e (p-Ni t rophenold i g t h y l p h o s p h a t , ,Mintacol\" , Bayer), die h e k a n n t l i c h eine P h o s p h o r y l i e r u n g des a k t i v e n Z e n t r u m s der Chol ines terase ve ru r sachen . Es gel ingt ngml ich , die A C h E d u t c h vorher ige ]3ehandluug m i t Arsen i t vo r der i r revers ib len H e m m u n g m i t p N i t r o p h e n o l d i ~ t h y l p h o s p h a t we i tgehend zu schfi tzen. Mit Arsen i t g e h e m m t e und d a n a c h m i t t . t 0 ~ p N i t r o p h e n o l di~Lthylphosphat behande l t e F e r m e n t l 6 s u n g e n k 6 n n e n nach d e m Herausd i a ly s i e r en der be iden Stoffe bis zu 85% ihrer an fgng l ichen A k t i v i t ~ t wieder erreichen, w~hrend Eermen~16sungen ohne vo rhe r igen Arsen i t zusa t z d u t c h p -Ni t ropheno l d i ~ t h y l p h o s p h a t vo l l s tgnd ig und i r revers ibel g e h e m m t werden. D u r c h nach t rgg t i che Dia lvse s ind sie n i ch t m e h r zu e n t h e m m e n .

J. D. Achelis

Papers

Raupin, ein neues Alkaloid aus Rauwolfia serpentina