1
COMPOUNDS AFFECTING CENTRAL NERVOUS SYSTEM
SEDATIVES
Calming CNS via suppression of increased irritability
Biogenic drugs of this group possess complex character
Effect is triggered after repeated application
VALERIANAE RADIX – VALERIAN ROOT
(ČL 2002)
Valeriana officinalis L. sensu
lato – valerian
(Valerianaceae)
• Perennial huge plant home
in Europe and Asia
• Polymorphous species
divided in to series and
types; differ both in
number of chromosomes
and content compounds
• For pharmaceutical
purposes cultivated
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VALERIANAE RADIX
• Drug is formed up to 40 0C dried
rhizomes with numerous roots and
spits
• Characteristic odor
• Un-cut drug - 5 ml essential oil/kg
• Cut drug - 3 ml essential oil/kg
• Contains at least 0,17 % of
sesquiterpenic acids counted as
valerenic acid, relative to dried
drug
VALERIANAE RADIX
CONTAIN COMPOUNDS – ESSENTIAL OIL
OR
H
OR
R
-COCH2CH(CH3)2
-COCH2CH2CH3
-COCH3
valeranon
valerenic acid R=COOH
valerenal R=CHO
borneol
-pinen camphen
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VALERIANAE RADIX
CONTENT COMPOUNDS – VALEPOTRIATES
(Valeriana epoxy triesters)
O
O
O
O
H
H
R2
R1
CH2
O R3
O
CH2OR
HCO
O
O
O
O
R2
R1
CH2
O R3
typ monoene typ diene R1 R2 R3
baldrinal, R=Ac
homobaldrinal, R=iVal
R1 R2 R3
didrovaltrate iVal Ac iVal valtrate iVal iVal Ac
isovaltrate iVal Ac iVal
acevaltrate iVal (-O-
-Ac)iVal
Ac
VALERIANAE RADIX
CONTENT COMPOUNDS
• Flavonoid gycosides derived from quercetine
• Traces of pyridine alkaloids (actinidine)
• Aminoacids glutamine, alanine, asparagine
-aminobutyric acid (8g / kg of extract)
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VALERIANAE RADIX
Valerianae tinctura – valerian tincture (ČL 2002 N)
Valerianae extractum fluidum – liquid valerian extract
Effect
• Valepotriates and their fissionable products – sedative,
tranquilizers
• Valerenic acid – musculotropic spasmolytic, sedative
• Sesquiterpenes – slowing degradation of GABA
Utilization:
• insomnia, nervousness, feelings of tension
• antispasmodic (gastric)
VALERIANAE RADIX
• Drug is a part of herbal mixture ( VALOFYT NEO, NERVOVÁ
ČAJOVÁ SMĚS)
• Extract is part of sedative and spasmolytic mixtures
• Valepotriates are part of sedatives and tranquilizers (VALMANE,
BALDRISEDON)
Production of valepotriates:
• Valeriana wallichii DC.– cultivated in India; contains 2,8-3,5 %
of valepotriates
• Valeriana edulis ssp. procera – cultivated in Mexico; contains up
to 7 % of valepotriates
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MELISSAE FOLIUM – LEMON BALM LEAVES (ČL 2002)
Melissa officinalis L. – Lemon balm
(Lamiaceae)
• Perennial plant with branched
stem
• White stalked flowers in valleys
of leaves
• Cultivated in middle and south
Europe
Drug: dried leaves harvested at the
biggining of flowering period
Temperature of drying could not
exceed 35 0C
Characteristic lemon odour
MELISSAE FOLIUM
CONTENT COMPOUNDS – POLYPHFENOLS
Contains at least 4,0 % of all
hydroxycinnamate
derivatives, expressed as
rosmarinic acid („tannin“ of
plants from Lamiaceae)
OH
OH C
H
C
H
C O
O
CH
COOH
C
H2
OH
OH
Rosmarininc acid
(depsid of caffeic acid with 3,4-dihydroxyphenyl lactic acid)
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MELISSAE FOLIUM
CONTAIN COMPOUNDS – ESSENTIAL OIL
CHO CHO
CHO
OH
citronellal neral geranial linalool -caryophylene
citral
MELISSAE FOLIUM
FURTHER COMPOUNDS
• sesquiterpenes copaene,
cubebene
• Ursolic acid
• flavonoid rhamnesine
• coumarin aesculetine
EFFECT mild
• sedative
• spasmolyticc
• antiphlogistic
• antibacterial
UTILIZATION
Mostly often used for herbal tea
mixtures
Use at neurovegetative dystonia
(cardial, stomachic, intestinal
disorders)
Component of carminative mixtures
Water extract externally to affect
skin
Cosmetics
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MELISSAE FOLIUM
ESSENTIAL OIL IS NOT OBTAINED FROM MELLISAE FOLIUM DUE
TO THE RELATIVELY LOW CONTENT
Under naming MELISSAE OLEUM could be:
• Essential oil from indian herb Cymbopogon spp. – lemon grass
(Poaceae), correct naming is Oleum citronellae
• Citrus essential oil obtained from pericarpium Citrus limonum –
Mediterranean sweet limetta (Rutaceae)
• Through Melissae herba hydrodistilled Citrus essential oil –
Oleum melissae citratum
LUPULI FLOS – HOPS (ČL 2002)
Humulus lupulus L. – common
hop (Cannabaceae)
• dioecious, dextrorotary
wrapping climbing plant
• Cultivated in Europe and
Northern Asia
• Only female plants are
cultivated
• Vegetative propagation
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LUPULI FLOS
Drug: dried, usually whole
female inflorescences
Characteristic aromatic odour
Must contain at least 25,0 % of
compounds extractible by
ethanol 70% (V/V)
Protect against sunlight.
Drug non-pharmacopoeic:
Lupulinum – Lupuline,
Glandulae lupuli – hop
glandules, yellow colored
powder, bitter taste and
aromatic odor
Stored maximally one year
Protect against sunlight.
LUPULI FLOS
CONTENT COMPOUNDS – ESSENTIAL OIL (0,3 - 1 %)
C
H
C
H2
COOR
CH3
CH3
myrcene humulene farnesene
esters isobutyric acid
oxygenated monoterpenes in traces only
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LUPULI FLOS
CONTAIN COMPOUNDS – RESINS (15 - 30 %)
OH
O OH
OH
R
O
R
O
OHO
OH
-lupulic bitter acids
monoacylphloroglucinols with 2 prenyl units
humulone, R=CH2CH(CH3)2
cohumulone, R=CH(CH3)2
adhumulone, R=CH(CH3)CH2CH3
-lupulic bitter acids
monoacylphloroglucinols with 3 prenyl units
lupulone, R=CH2CH(CH3)2
colupulone, R=CH(CH3)2
LUPULI FLOS
CONTENT COMPOUNDS - FLAVONOIDY
OHOH
OH
OMe O
OOH
OH
OMe O
OOH
OH
OH O
xanthohumol
(chalcone)
isoxanthohumol
(flavanone)
rutosid
quercitrin
astragalin
flavonoids:
8-prenylnaringenin
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LUPULI FLOS
PRODUCTS OF PRENYL DEGRADATION
OOH
OH
OMe O
OHO
OH
R
O
CH2
C
C
H
CH3
CH3 OH
OH
OH
isoxanthohumol
(flavanon)
-lupulinic bitter acids
monoacylphloroglucinols with 3 prenyls
lupulone, R=CH2CH(CH3)2
colupulone, R=CH(CH3)2
3-methyl-1-butene-3-ol
3-methyl-1-pentin-3-ol
(ALLOTROPAL)
LUPULI FLOS and LUPULINUM
UTILIZATION
• Sedative
• Anaphrodisiac (antigonadotropic glucoprotein)
• Amare (bitter lupulinic acids)
• Stomachic
• Antidiabetic for beginning stadia (decoction from hops)
• Beer manufacturing
O O
OH
OH
O
trans-isohumulon
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PASSIFLORAE HERBA – PASION FLOWERS
HERB (ČL 2002)
Passiflora incarnata L. – passion
flowers (Passifloraceae)
Perennial, climbing, evergreen with
bright purple flowers
Home in Middle and South America
In Europe planted as ornamental
Drug: cut dried aerial part, may
contain also flowers and/or
fruits
Contain at least 1,5 % of total
flavonoids (expressed as
vitexin) related to dried drug
PASSIFLORAE HERBA – CONTAIN COMPOUNDS
• Flavonoid C-glycosides: vitexin,
isovitexin, orientin, isoorientin,
vicenin, lucenin
• Carboline alkaloids: harman,
harmol, harmin
• Maltol (2-methyl-3-hydroxy-γ-
pyron)
Utilization: sedative, insomnia
O
Glc
OH
OH
OH
OH
O
N
H
N
CH3
O
O
OH
CH3
vitexin
harman maltol
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HYPERICI HERBA – St. JOHN´S WORTH HERB
(ČL 2002)
Hypericum perforatum L. – St.
John´s worth (Hypericaceae)
• Perennial plant of all continents
• Species naming – bright pointing
of leaves – secretion glandules
Drug – whole or cut flowering tips of
plant, harvest VII and VIII, drying
at 35 0C, storage – protect against
sunlight.
Contain at least 0,08 % of all
naphtodianthrones, counted as
hypericin, related to dried drug
HYPERICI HERBA
Hypericum species – St.
John´s worth in Czech:
H. perforatum L. (ČL 2002)
H. maculatum Crantz.
H. montanum L.
H. hirsutum L.
H. pulchrum
H. tetrapterum Fries
H. elegans Steph. ex Wild.
H. humifusum L.
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HYPERICI HERBA – CONTENT COMPOUNDS
1. Naphtodianthrons 0,1-0,15 % (hypericine, pseudohypericine,
isohypericine, protohypericine, protopseudohypericine)
2. Flavonoids 2-4 % (hyperosid, quercetin, isokvercitrin, rutosid, kempferol,
luteolin, myricetin)
3. Biflavonoids (I3,II8-biapigenin, I3’,II8-biapigenin = amentoflavon)
4. Phloroglucinol derivatives (hyperforin, adhyperforin)
5. Tannins 5,5-15 % (catechine type), including precursors: catechine,
epicatechine, procyanidine and leucoanthocyanidine
6. Essential oil 0,1-1 % (higher alkanes, mono- and sesquiterpenes, mainly
α-pinen and caryophylene)
7. Xanthones (1,3,6,7-tetrahydroxyxanthon)
8. Organic acids (caffeic, ferulic, quinic)
HYPERICI HERBA – NAPHTODIANTHRONES
OOH OH
OOH OH
OH
OH
CH3
CH3
hypericine
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HYPERICI HERBA – FLAVONOIDS
O
OR
O
OH
OH
OH
OH
hyperoside R = -D-Gal
quercitrine R = -L-Rha
isoquercitrine R = -D-Glc
rutoside R = -D-Glc(6 --1)-L-Rha
HYPERICI HERBA – BIFLAVONOIDS
OOH
OH
OH
O
OOH
OH
OH
O
I3',II8-biapigenine (amentoflavone)
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HYPERICI HERBA – DERIVATIVES OF
PHLOROGLUCINOL
OHO
O O
CH3
OH
hyperforin
3-methyl-1-buten-3-ol
HYPERICI HERBA – USAGE
Sedative (JARSIN, HYPERFORAT, ESBERICUM)
Therapy of depression (inhibition of MAO, increased secretion of
serotonin and melatonin ?? Do not combine with other
antidepressives!
Antivirotic (light exposition is condition) HSV1, HSV2,
cytomegalovires – inhibition of reversed transcriptase, integrase
Baktericide (G+ and G-)
Astringent (tannins)
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HYPERICI HERBA – SIDE EFFECTS
Photodynamic effect (hypericismus), albinoids
Mutagenic effect of Oleum hyperici
Affects:
• Decrease of theophyline effect (asthmatics)
• Decrease of warfarine and cyclosporine effectiveness
• Together with hormones (ethinylestradiol + desogestrel) –
bleeding
LAVANDULAE FLOS – LAVENDER FLOWERS (ČL 2002)
LAVANDULAE OLEUM – LAVENDER ESSENTIAL OIL (ČL 2002)
Source: Lavandula angustifolia –
lavender, Lamiaceae
• Perennial low shrub with
integerrime leaves with under
winded margin. Small blue
slothy flowers
• Must contain at least 13 ml of
essential oil / 1 kg of drug
• Essential oil is obtained by
hydrodistillation
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LAVANDULAE FLOS – LAVENDER FLOWERS (ČL 2002)
LAVANDULAE OLEUM – LAVENDER ESSENTIAL OIL (ČL 2002)
CONTAIN COMPOUNDS
OCOCH3 OH
H
CH2
OH
O
OH
Components of essential oil
linalylacetate
30 - 60 %
linalool geraniol limonen cineol
borneol
Other contain compounds:
tannins
anthocyanins
LAVANDULAE FLOS – LAVENDER FLOWERS (ČL 2002)
LAVANDULAE OLEUM – LAVENDER ESSENTIAL OIL (ČL 2002)
Usage:
• mild sedative
• carminative
• spasmolytic
Externally:
• derivant
• corrigents of odor
Largest consumption: manufacturing of alcohol, perfumeries
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KAWA-KAWA
Source: Piper methysticum –
pepřovník opojný
• Shrub home and cultivated
at islands of Micronesia and
Polynesia
• From fresh roots the water
extract is prepared. The
extract is used for ritual
ceremonies
Drug: dried and cut rhizomes
without roots
KAWA-KAWA
CONTENT COMPOUNDS
O O
OMe O
R
OH
OMe
MeO
R1 =R2 = Hkawaine
1 26
7
8
11
12
methysticine R1 - R2 = - OCH2O -
R1
R2
(derivatives of -pyrone)
flavokavine A R = OCH3
flavokavine B R = H
(chalcones)
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KAWA-KAWA
Effect:
• sedative or hypnotic in dependence on dose
• Derivatives of α-pyrone and its 7,8-dihydroderivatives – central
suppression, similar to ataractics
• analgesic
• anticonvulsive
GUMMIRESINA ASA FOETIDA –
KLEJOPRYSKYŘICE ASA FOETIDA
Source:
Ferula asa foetida – asafetida
(Apiaceae)
• perennial herb of steppes of
Iran and Afghanistan
• flowing from roots after
cutting, after desiccation is
collected
• disgusting odor
Usage:
• sedative (during hysteria)
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GUMMIRESINA ASA FOETIDA
ASAFETIDA GUMMIRESIN
CONTAIN COMPOUNDS
C
H
CH2
S
CH3 CH3
S
CH2
CH
CH2
O
O
CH2
OH
O
H
CH C
H
OH
OMe
COOH
O O
OMe
isobutylpropenyldisulfide
foetidine
ferulic acid
4-methoxycoumarin
AVENAE FRUCTUS – OAT FRUITS (FLAKES)
Source:
Avena sativa – common oat
(Poaceae)
One-year cultivated plant
Extraordinary rich
heterogeneous mixture of
content compounds
Usage:
component of sedative
mixtures
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AVENAE FRUCTUS – OAT FRUITS
CONTAIN COMPOUNDS
• Saccharides: starch, -glucans, arabinoxylans, cellulose
• N-substances: proteins, lipoproteins, peptids
• Sterols: avenasterols, -sitosterol, stigmasterol
• Steroid saponins: avenacosid A a B
• Vitamins: B1, B2, B6, pantothenic acid, vitamine E, vitamine K
• Minerals: cca 30 % silicic acid
• Others: gramin, linamarin, pheophytine, avenein = vanililglucoside
AVENAE FRUCTUS – OAT FRUITS
CONTAIN COMPOUNDS
O
O
O
O -D-Glc
-D-Glc-(4--1)-Rha
(2--1) -D-Glc
Avenacosid A
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VALOFYT-NEO
Valerianae radix 24 g
Lupuli flos 12
Melissae herba 11
Avenae fructus 11
Lavandulae herba 11
Crataegi fructus 17
Salicis cortex 7
Angelicae radix 3,5
Menthae piperitae herba 3,5