COMPOUNDS AFFECTING AUTONOMOUS (VEGETATIVE)
NERVOUS SYSTEM
Chemical transmission between neurons is mediated using transmitters
(neurotransmitters).
Transmitters are deliberated from neuronal terminations into space of synapsys,
they cross synapses and activate or inhibit postsynaptic cells by binding to
specialized molecules of receptors.
Autonomous neural system is into some rate independent and its activity is not
under control of will.
It affects processes: heart activity, tonus and motility of smooth muscles,
digestion, glandular secretion, eye control…
ANS – part of neurohumoral regulatory system, which in coordination with CNS
adapts reactions of organism to changes of inner and outer environment
PERIPHERAL PART OF AUTONOMOUS NEURAL SYSTEM NERVES
SYMPATIC AND PARASYMPATIC
PARASYMPATICUS
• participates on anabolic processes
• Increases secretion of digestive
tract and its motility
• increases stock of storage
compounds (glycogene)
• tranquilize heart action
• Increases the blood supplies of
organs
Mediator is acetylcholine
SYMPATICUS
• Mobilizes to sharp deffensive and
adaptation reactions
• accelerates heart action
• increases blood pressure
• Trgggers utilization of storage
compounds
Mediator is noradrenaline
Component of system is adrenal gland
→ adrenalin
OH
OH
C
C
H2
OH
NH2
H
OH
OH
C
C
H2
OH
N
H
H
CH3
adrenalinenoradrenaline
NCH3
CH3
CH3
CH2 CH2 O C CH3
O
+
Cl
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DIVISION OF COMPOUNDS AFFECTING AUTONOMOUS NEURAL
SYSTEM
SYMPATOTROPIC COMPOUNDS
• sympatomimetics
(adrenomimetics, adrenergic compounds)
working as sympaticus irritation
• sympatolytics
(adrenolytics, adrenergic blockers,
antiadrenergic compounds)
block effects of sympaticus stimulation,
sometimes block effects of
sympatomimetics
PARASYMPATOTROPIC COMPOUNDS
• parasympatomimetics
acting as parasympaticus irritation
• parasympatolytics
block parasympaticus stimulation and block effects
of parasympatomimetics
DIRECT SYMPATOMIMETICS
NOREPINEPHRINE =
NORADRENALINE (ČL 2005)
Natural mediator
Usage:
• Peripheral analeptic for
treatment of collapses
• During intoxication by hypnotics
or narcotics
EPINEPHRINE = ADRENALINE
(ČL 2005)
Hormone of medulla of adrenal
gland
Usage:
• Peripheral analeptic for
treatment of collapses
• During intoxication by hypnotics
or narcotics
• Vasoconstringent admixture to
local anesthetics solutions
• Bronchodilator
• Antiallergic
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INDIRECT SYMPATOMIMETICS INCREASE IN PLCE OF EFFECT
LEVEL OF NEUROMEDIATOR
EPHEDRINUM – EPHEDRINE (ČL 2005)
Ephedrini hydrochloridum – Ephedrine HCl
Source: Ephedrae herba – mahuang herb
Ephedra sinica - Joint-pine, Jointfir,
Mormon-tea, mahuang; E. distachya –
(Ephedraceae). Broom-like
gymnosperm shrubs with coupled
scale-like leaves
Drug: in autumn harvested dried branches,
brown-green colour. Producers: China,
India, Pakistan, Spain)
CC: 0,5-1,5 % of alkaloids (cca 75 % of
ephedrine), tannins, saponins
Usage: antiasthmatic, analeptic, peripheral
vasoconstringent, central stimulant
Ephedrinism
C
C
N
H
CH3
H
H
OH
CH3
HCl.
(1R,2S)
INDIRECT SYMPATOMIMETICS
KHAT
Source: Catha edulis – khat (Celastraceae).
Evergreen shrub native to Yemen, Ethiopia
and Solmalia. Natives chew fresh leaves -
khat.
Drug: dried leathery leaves
CC: norpseudoephedrine = cathine, cathinone,
flavonoids
Effects: euphoria, after repeated use starts
addiction
loss of appetite
cathine – lead compound for synthetic
anobesics
C
C
NH2
H CH3
OHH
C
C
NH2
H CH3
O
cathine cathinone
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SYMPATOLYTICS – ADRENOLYTICS
SYMPATOLYTICS BLOCKS ADRENERGIC REACTIONS.
AS DIRECT SYMPATOLYTICS, BLOCKING
α1 ADRENERGIC RECEPTORS ACT
NATIVE AND DH-DERIVATIVES OF ERGOT ALKALOIDS
SECALE CORNUTUM – ERGOT
Source: Claviceps purpurea – ergot (Clavicipitaceae) – fungus parasiting
on the rye and some other plants of Poaceae family
Fungal attack changes the ovaria of plants to thought, dark-purple
sclerotia.
Ergot is used as a therapeutical agent from medieval ages.
• 1808 Stearns in USA – effect of ergot on the management of labor
• 1875 Tanret in France – first crystalline product from ergot
• From 1917 Stoll and Hoffmann in Sandoz Co. – obtained pure alkaloids
and enabled their application in therapy.
• From 1954 M. Semonský in VÚFB – antimigraenics, venopharmacs
• Today known more than 50 native alkaloids
• Numerous derivatives and semi-synthetic derivatives
• Research continues
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SECALE CORNUTUM – ERGOT
SECALE CORNUTUM – ERGOT
Increased consumption of ergot alkaloid is solved:
• by increasing of sown area
• by artificial infection of rye (preparation of material with
conidias of required type – ergotamine, ergotoxine or
ergocristine), 6-8 weeks after infection sclerotia are harvested
• by using in vitro saprophytic culture
Paspalum dilatatum (strain Claviceps paspali) produce during
submersal cultivation up to 10 % of free lysergic acid, which
can be used for preparation of semisynthetic analogues
In present time submersal cultivation and production of ergotoxine
type
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SECALE CORNUTUM – ERGOT
CONTENT COMPOUNDS
• Hemiterpenic indol alkaloids
- clavines – derivatives of 6,8-dimethylergoline
- amides
- peptides of lysergic acid
• Further compounds
- building material of cell walls
- fatty oil up to 35 %
- ergosterol
- tyramin, histamin
- pigment (clavorubine, ergoflavine, secalonic acid)
SECALE CORNUTUM – ERGOT
NH
N
H
H
H
N
N
H
HH
CH3
COOH
N
N
H
H
CH3
H
HOOCN
N
H
H
CH3
CH3
R
R
ergoline lysergic acid
(5R, 8R)
isolysergic acid
(5R, 8S)
1
2
3
45
6
7
8
9
10
11
12
13
14
15
16
A B
C
D
clavine
R = H, OH
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LYSERGIC AND ISOLYSERGIC ACID IN SPACE
N
H
N
CH3
H
H
COOH
N
H
N
CH3
HH
HOOC
1
2
3
4
56
78
9 10
1112
13 A
B
C
D
14
(5R,8R) lysergic acid (5R,8S) isolysergic acid
active alkaloids, suffix - ine
for example: ergometrine
non-active alkaloids, suffix - inine
for example: ergometrinine
SECALE CORNUTUM – ERGOT
CLAVINE ALKALOIDS
Clavine alkaloids number ≥ 20
• carboxylic group at C8 reduced to
primary alcoholic group or to methyl
group
• not used in therapy
• subject of studies
N
N
H
H
CH3
CH2OH
OH
peniclavine
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SECALE CORNUTUM – ERGOT
LACTAM PEPTIDE ALKALOIDS
N
N
O
O
N
H
N
N
H
HH
CH3
OC
CH
H CH2
O
CH3
CH3
ergocristame
SECALE CORNUTUM – ERGOT
SIMPLE AMIDES
N
N
H
HH
CH3
CO-R
CH3
-CH(NH)2
-CH2
OH
Ergine R = NH2
Ergometrine R =
uterotonic
N
N
H
HH
CH3
CO-NH-CH2
CH2
OH
-hydroxyethylamide of lysergic acid
Paspalum dilatatum, submersal cultures
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ERGOT ALKALOIDS PEPTIDIC
ERGOTAMINE AND ERGOTOXINE GROUP
N
N
O
O
N
H
N
HH
CH3
OC
R1
H R2
O
proline
aminoacid
ketoacid
2'
5'
-hydroxyvaline -CH3
-amino-N-butyrate - C2H5
-hydroxyvaline -CH(CH3)2
phenylalanine - CH2-C6H5
leucine - CH2CH(CH3)2
isoleucine - CH(CH3)C2H5
valine - CH(CH3)2
N
N
O
O
N
H
N
N
H
HH
CH3
OC
R1
H R2
O
CH3
C
H2
CH3 CH
CH3
CH3
C
HCH3 CH3
CH2
C
HCH3
CH3
CH CH3
CH2
CH3
C
H2
proline
aminoacid
ketoacid
ergotamine
group
ergostine
group
ergotoxine
group
2'  R1
5'  R2
ergovaline ergonin ergocornine
ergosine ergoptin ergocryptine
-ergosin -ergoptin -ergocryptine
ergotamine ergostine
2'
5'
ergocristine
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ERGOT ALKALOIDS – USAGE
ISOLATED ALKALOIDS AND THEIR DERIVATIVES
block α1-adrenergic receptors
Ergometrini maleas – Ergometrine-maleinate (ČL 2005)
• Uterotonic
Ergotamini tartras – Ergotamine-tartrate (ČL 2005)
• Uterotonic
• Component of antimigrainics and sedatives
Methylergometrinium tartaricum – Methylergometrine-tartrate
• Uterotonic
Dihydroergocristini mesilas – Dihydroergocristine-mesylate (ČL 2005)
• Alpha-sympatolytic – for therapy of peripheral blood supply, vasodilatant.
• Component of antihypertensives
Dihydroergotamini mesilas – Dihydroergotamine-mesylate (ČL 2005)
• Alpha-sympatolytic- for disorders of peripheral blood supply
• Antimigrainic
α2-RECEPTOR BLOCKER - YOHIMBINE
Source: Pausinystalia yohimbe – yohimbe
(Rubiaceae). Up to 30 m tall tree from
Cameroon and Congo
Drug: dried bark of stems and branches
CC: alkaloid 1-1,5 %, main is yohimbine
(trans anelation of rings C/D and D/E)
tannins
Bark is used for alkaloids isolation
Effect: yohimbine dilates peripheral blood
vessels and lowers blood pressure
Usage:
• rarely as antihypertensive
• adjuvant during impotentia coeundi of
neurastenic origin
• aphrodisiac
N
H
N
H H
H
OH
OOCCH3
A B C
D
E
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PARASYMPATOMIMETICS
DIRECT PARASYMPATOMIMETICS
• Pilocarpine
• Arecoline
• Muscarine
• Nicotine in small doses
INDIRECT PARASYMPATOMIMETICS
(reversible inhibitors of acetylcholin-
esterase)
• Physostigmine
• Galanthamine
PILOCARPINI NITRAS – PILOCARPINE-NITRATE (ČL 2005)
PILOCARPINI HYDROCHLORIDUM – PILOCARPINE-HYDROCHLORIDE (ČL2005)
Source: Pilocarpus jaborandi – jabornadi, P.
racemosus, P. microphyllus (Rutaceae);
shrubs and small trees from South
America (Brazil, Paraguay)
Drug: dried, leathery, ellipsoid leaves. Bright
points show through – glandules with
essential oil. Storage rapidly decreases the
alkaloid content
CC: 0,5-5 % alkaloids – substituted imidazols.
Prevalent pilocarpine. Stable at pH 3-5.
Effect: Increases secretion of salivary and
perspiratory glands, induces miose and
lowers intraocular pressure
Usage: glaucoma, hydragogum for acute
hydrops of labyrinth, rarely diaphoretic
O
HH
C2
H5
O
N
N
CH3
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ISOMERISM OF PILOCARPINE
AT BUTYROLACTONE RING
OO
R H
H R
trans = iso-compounds
not effective
OO
H H
R R
cis = normal form
stable at pH 3 - 5
PHYSOSTIGMINI SALICYLAS – PHYSOSTIGMINE-SALICYLATE (ČL2005)
PHYSOSTIGMINI SULFAS – PHYSOSTIGMINE-SULPHATE (ČL 2005)
Source: Physostigma venenosum –
calabar bean (Fabaceae); climbing
wine from tropic West Africa. Fruit is
a pod containing seeds
Drug: kidney-shaped, pale, dark-brown
seeds (resembling beans). Used for
physostigmine isolation.
CC: 0,1-0,2 % alkaloids, main is
physostigmine (syn. eserine).
Further fatty oil. At pH ≥ 5
hydrolysis producing ineffective
compounds
Effect: reversible inhibitor of
acetylcholinesterase
Usage: miotic during glaucoma, less at
atonia of internal organs and for
treatment of neurologic disorders
N N
OCN
OH
CH3
CH3
H
CH3 CH3
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GALANTHAMINUM – GALANTHAMINE
Source: Galanthus nivalis – snowdrop
(Amaryllidaceae). Perennial plant of humid
mountain meadows and deciduous woods
Drug: up to 3 cm big bulbs, processed fresh for
alkaloid isolation
CC: norballadine alkaloids, their content and
spectrum is variable; mucilage, starch, organic
acids
Effect: reversible inhibitor of acetylcholinesterase
Usage:
• ophthalmology at glaucoma
• post-surgical paresis
• paralysis of guts and bladder
• Damage of central motoric neurons
• status after poliomyelitis
• neurodenerative diseases
Alternative sources: Galanthus woronovii (Caucasus)
Ungernia victoria (South America)
O
N CH3
OH
MeO
MUSCARINE
Source: Amanita muscaria – fly agarics
(Agaricaceae)
Effect: Affects exclusively at receptors of
peripheral effectoric cells of
parasympaticus (therefore assignation of
these receptors – muscarine type, M-
receptors)
Toxicological importance, causes:
• miose
• diarrhea, convulsions
• bronchoconstriction
• Decrease of blood pressure leading to
collapse
• Increase of glandular secretion
Usage: experimentally
OCH3
OH
N(CH3
)3
+
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ARECOLINUM – ARECOLINE
Source: Areca catechu – areca nut palm, Betel,
(Palmae); slim stem terminated by bunch of
fan-shaped leaves; India, southeast Asia;
cultivated in India, Bangladesh, Indonesia, east
Africa - Tanzania
Drug: Arecae semen – areca nut, seed Ø 2 cm
embedded in fibrous drupe
CC: 0,2-0,5 % of alkaloids, main is arecoline; 50-60
% of sugars; 15 % fats; tannins; flavans
Effect: arecoline targets M-receptors. Causes
• miose
• stimulation of peristaltic
• Increases salivation
Usage:
• Diaphoretic
• Veterinary anthelmintic, taenicide
• For chewing ≥ 200 millions of people for
psychoactive effect
• Tested for treatment of neurodegenerative
diseases
N
CH3
O
OCH3
NICOTINE
Source: Nicotiana tabacum, N. rustica – tobacco
(Solanaceae); cultivated for production of
leaves to smoke, chew and snuff.
CC: 2-10-15 % of alkaloids, main is
(S)-(–)-nicotine = volatile liquid base;
anabasine, nornicotine and others, 40 % of
saccharides (starch, pectin, cellulose, sugars),
15-20 % organic acid
Effect:
• at low doses stimulates, at high doses blocks
ganglia (nicotine cholinergic receptor)
• stimulates CNS - addiction
• Increases motility and secretion of GIT
Toxicological importance
Insecticide
N
N
CH3
H
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PARASYMPATOLYTICS AND SPASMOLYTICS
PARASYMPATOLYTICS – compounds blocking muscarinic effects of
acetylcholine and cholinomimetics.
Induce:
• spasmolysis
• mydriasis, accomodation paralysis
• Decrease of secretion of glands - salivary, perspiratory, bronchial,
gastric
• tachycardia (above 90 strokes / min)
SPASMOLYSIS – release of pathologically increased contractibility of
smooth muscles and peristaltic
• GIT
• urinary tract
• biliar ways
SPASMOLYTICS
NEUROTROPIC
anticholinergic, atropine type
Affect parasympatic inervation
of smooth muscle
Atropine, scopolamine
MUSKULOTROPIC, myotropic,
papaverine type
Release convulsions by direct
affecting of cells of smooth
muscles
Papaverine, khelline
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TROPANE ALKALOIDS – NEUROTROPIC SPASMOLYTICS
N
CH3
N
CH3
OH
H
N
CH3
O
H
CO
C
CH2
OH
H
N
CH3
O
H
CO
C
CH2
OH
H
C
H
HOH2
C COOH
C
CH2
COOH
atropic acid
(-)-S-tropic acid
tropane
tropanol
(tropan-3--ol)
-H2O
(-)-S-hyoscyamine (+)-R-hyoscyamine
D-hyoscyamine
1 2
3
4
5
6
7
L-hyoscyamine
TROPANE ALKALOIDS – NEUROTROPIC SPASMOLYTICS
N
O
HR4
R3
R1
R2
O
O
O
O
tropanol CH3 H H H
hyoscyamine CH3 tropoyl H H
norhyoscyamine H tropoyl H H
apoatropine CH3 atropoyl H H
valeroidine CH3 isobutyryl OH H
meteloidine CH3 tigloyl OH OH
scopine CH3 H
scopolamine CH3 tropoyl
norscopolamine H tropoyl
aposcopolamine CH3 atropoyl
R1 R2 R3 R4
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TROPANE ALKALOIDS – NEUROTROPIC SPASMOLYTICS
C
O
O T
N
CH3
O
H
C
O
OT
belladonine
tropylT
=
BELLADONNAE FOLIUM – DEADLY NIGHTSHADE
LEAVES (ČL 2005)
Source: Atropa belladonna – deadly nightshade
(Solanaceae). Perennial 1,5 tall herb, Europe,
for pharmaceutical purposes is cultivated
Drug: dried leaf sometimes with flowering or
fruit bearing tips, harvested VI-VIII
CC:
• 0,2-1 % tropane alkaloids, (-) Shyoscyamine,
racemizing to atropine;
scopolamine (hyoscine); during drying is
formed apoatropine and via further
dimeriztion belladonine
• coumarins scopoline and scopoletine
• flavonoids, tannins
• Sand of CaOx
Usage: for isolation of alkaloids and preparation
of chosen galenic
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BELLADONNAE RADIX – DEADLY NIGHTSHADE ROOT
Source: as Folium belladonnae
Drug: dried, cylindric, cut roots. Externally
grey-brown, inside grey-white, when
broken produce dust - starch.
Cultivated, harvest of plant 3-4 years old
CC:
• 0,4-0,8 % tropane alkaloids, (-) Shyoscyamine,
atropine; scopolamine;
apoatropine, belladonine, hygrines
• coumarins scopoline and scopoletine
• starch
• sand of CaOx
Usage: for isolation of alkaloids and for
preparation of galenic
NN C
H2
C
C
H2
O
CH3
CH3
O
R
OMeO
cuscohygrine
scopoletine R=OH
scopoline R=O-Glc
STRAMONII FOLIUM – THORN APPLE LEAVES (ČL
2005)
Source: Datura stramonium – thorn
apple (Solanaceae); one-year herb,
weed. For pharmaceutical purposes
is cultivated. Spectacular with
flowers and big fruits
Drug: dried, thin, fragile leaves, harvest
V-IX;
CC: 0,1-0,6 % of tropane alkaloids, (-)S-hyoscyamine,
scopolamine; less
apoatropine, belladonine
• coumarins scopoline and scopoletine
• flavonoids, tannins
• aggregates CaOx
Usage: for isolation of alkaloids and for
preparation of galenics
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HYOSCYAMI FOLIUM – HENBANE LEAVES
Zdroj: Hyoscyamus niger – henbane
(Solanaceae); biennial herb from rubbles;
cultivated one-year form
Drug: dried pale gray-green, from both side
trichomous toothed leaves, VI-VIII.
CC:
• 0,03 – 0,15 % tropane alkaloids
hyoscyamine, scopolamine
• flavonoids, tannins, coumarins
• crystalls of calcium oxalate
Usage: material for alkaloid isolation
More benefits from in Egypt cultivated
Hyoscyamus muticus, contaning up to 1,5
% of alkaloids
FURTHER SOURCES OF TROPANE ALKALOIDS
Hyoscyamus muticus (Egypt), Herb contains 0,6-1,5 % of alkaloids
Scopolia carniolica (Balcan peninsula, Rusia), root contains 0,4-1 % of alkaloids
Duboisia myoporoides (Australia), Folium containns up to 4 % of alkaloids
Leichardtii
Datura arborea (South America), Folium contains up to 0,4 % of alkaloids
Datura metel (Africa, trop. Asia), Folium contains cca 0,55 % of alkaloids
Occurrence in plants of Convolvulaceae, in some fungi (Sclerotinia, Corticium)
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MUSCULOTROPIC SPASMOLYTICS
Papaverini hydrochloridum – Papaverine hydrochloride (ČL 2005)
Source: Opium (0,5-1,3 %); poppy straw
Usage: spasmolytic effects is observed at smooth muscles of:
• GIT
• Cardiovascular system
• Respiratory tract
• Urinary tract
MeO
MeO
N
OMe
OMe
HCl.
MUSCULOTROPIC SPASMOLYTICS
VISNAGAE FRUCTUS – KHELLA FRUIT
Source: Ammi visnaga – bisnaga,
toothpickweed, khella (Apiaceae);
one-year, 80 cm tall herb;
Mediterranian.
Producers: Egypt, Maroc, south of USA
Drug: dried ellipsoid doubled-achenes 2
mm long
Contain compounds:
• Furanochromones (1,5-3 %)
• Pyranocoumarins (0,2-0,6 %)
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MUSCULOTROPIC SPASMOLYTICS
VISNAGAE FRUCTUS – KHELLA FRUIT
Khellin –furanochromone derivatives
Usage:
• spastic bronchitis
• asthma bronchiale
• angina pectoris
• Intestinal, biliar and kidney colic
Visnadine – pyranocoumarine derivatives
Usage:
Coronary vazodilatant (increases flow through
coronary blood vessels)
O O
O
CH3
OMe
OMe
O
O
O
CH3
CH3
O
O-CO-CH3
COCH(CH3
)C2
H5
CHELIDONII HERBA – TETTERWORT HERB (ČL 2005)
Source: Chelidonium majus – greater
celandine, tetterwort (Papaveraceae);
Perennial herb of Europe and Asia.
Lactifers – orange colored latex containing
alkaloids and proteolytic enzymes (etches
eye cornea)
Drug: dried whole or cut flowering herba
CC: at least 0,6 % of alkaloids expressed as
chelidonine; alkaloids bonded on
chelidonic acid; contain of alkaloids in %:
roots 0,1-1,4; herb 0,01-0,5; fruits 0,6-
1,5; seeds 0
O
O
COOHHOOC
kyselina chelidonová
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CHELIDONII HERBA – TETTERWORT HERB (ČL 2005)
ALKALOIDS
N
O
O
OMe
OMe
+
berberin - choleretikum
1) Berberinový typ
N
O
O
O
O
O
CH3
N
O
O
O
CH3
OMe
OMe
2) Protopinový typ
protopin
allokryptopin
CHELIDONII HERBA – TETTERWORT HERB (ČL 2005)
ALKALOIDS
N
O
O
OH O
O
CH3 N
O
O
CH3
OMe
MeO
NH2
N
O
O
CH3
O
O
3) Benzofenanthridinový typ
+
chelidonin chelerythrin
stilbylethylamin
+
sanquinarin
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CHELIDONII HERBA – TETTERWORT HERB (ČL 2005)
Effect:
• weak central sedative
• spasmolytic
• choleretic
• cytotoxic
• antibacterial ( G+)
• high toxicity of alkaloids, proteolytic enzymes
Usage:
• spasmolytic
• choleretic
• inoperable gut polyposes
National pharmacopoeias list CHELIDONII HERBA RECENS
RUTAE HERBA – COMMON RUE AERIAL PART
Source: Ruta graveolens – common rue
(Rutaceae); evergreen shrub of
Mediterranean; cultivated; on the
leaves trichomes containing
dermatotropic essential oil
Druga: dried aerial part harvested before
flowering V, VI
CC: 0,05-0,15 % of alkaloids, 0,05-0,7 %
of essential oil (pinene, limonene,
cineol); furanocoumarins;
rutosid – first time discovered in this
plant
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RUTAE HERBA – COMMON RUE AERIAL PART
ALKALOIDS
N
O
O
OMe
N O
OMe
N O
OMe
MeO
N
CH3
O OH
OMe
OMe
N
H
O OMe
O
1) Chinolinový typ
graveolinin
2) Furochinolinový typ 3) Akridinový typ
diktamnin
skimmianin
arborinin
rutakridon
RUTAE HERBA – COMMON RUE AERIAL PART
BIOSYNTHESIS OF ALKALOIDS
NH2
COOH
NH2
CO-SCoA
CH3
CO-CoA
NH2
CO-CoA
O
N OH
OH
PP-O
N OH
OH
N
OR
O
kys. anthranilová
+ - CoA
aktivace aktivní acetát ketokyselina 2,4-dihydroxychinolin
+ IPP
3-dimethylallyl-2,4-dihydroxychinolin furanochinolin
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RUTAE HERBA – COMMON RUE AERIAL PART
PHOTOSENSIBILISING FURANOCOUMARINS
ÖÖ Ö
1
2
3
45
6
7
8
R1
R2
psoralen
xanthotoxin
imperatorin
bergapten
isopimpinellin
R1 R2
H
OCH3
O-CH2-CH(CH3)2
H
OCH3
H
H
H
OCH3
OCH3
RUTAE HERBA – COMMON RUE AERIAL PART
Effect:
• spasmolytic
• choleretic
• weakly uteroconstrict (alkaloids and furanocoumarins)
• during p.o. application increases uptake of blood into GIT
(spices of Mediterranean)
• Congestion of small pelvis – contraindication in pregnancy
Usage:
• folk medicine - spasmolytic; choleretic
• furanocoumarins – vitiligo, pigmentation disorders
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DRUGS AFFECTING PERIPHERAL NEURAL SYSTEM
LOCAL ANAESTHETICS
induce local anesthesia as a
result of reversible blockade
of excitement transmission
in sensitive neuron
• cocaine
• menthol
• eugenol
PERIPHERAL MYORELAXANTS
specifically brake
neuromuscular transfer of
irritation; lower tonus of
skeletal muscles and induce
its full slump and inability of
contraction
• curare (Menispermaceae)
• curare (Loganiaceae)
COCAINI HYDROCHLORIDUM – COCAINE HYDROCHLORIDE
(ČL 2005)
Source: Erythroxylum coca – coca
(Erythroxylaceae); evergreen shrub
(up to 5 m); widely do not grows;
It is cultivated as low shrub at 600-
1000 m above sea level, constant
temperature and humidity (Bolivia,
Peru, Columbia, Java)
Drug: dried leaves
• Huanuco - from Bolivia – big, dark
green leathery leaves
• Truxillo - from Peru and Columbia –
thin, smaller, bright green leaves
CC: 0,7-2,5 % of alkaloids derived
from pseudotropine, ekgonine,
hygrine;
tannins, essential oil
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ALKALOIDS PRESENT IN LEAVES OF ERYTHROXYLUM COCA
N
O
H
CH3
R1
R2
C6H5 C
H
C
H
C
H
C
H
C6H5CO
COOH
C6H5 C
H
C
H
C
H
C
H
COC6H5
COOH
ekgonin
benzoylekgonin
kokain
cinnamoylkokain
methylekgonin
tropakokain
R1
COOCH3
COOH
COOH
COOCH3
COOCH3
H
R2
H
OC-C6H5
OC-C6H5
OC-C6H5
H
OC-CH=CH-C6H5
-truxillin
-truxillin
COOCH3
COOCH3
ALKALOIDS PRESENT IN LEAVES OF ERYTHROXYLUM COCA
N
CH3
R NN C
H2
O
C
C
H2
CH3 CH3
hygrin, R=CH2COCH3
hygrolin, R=CH2CH(OH)CH3
kuskohygrin
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ALKALOIDS PRESENT IN LEAVES OF ERYTHROXYLUM COCA
HOOC
COOH
COOH
HOOC
N
N
C
O
O
CH3
H
H
COOCH3
O
O CH3
H
H
COOCH3
COOH
COOH
O
O
O
O
N
CH3
H
COOH
N
CH3
H
COOH
H
H
h
kyselina -truxillovákyselina skořicová
-truxillin
-truxillin
kyselina-truxillová
COCAINE
• COCAE FOLIUM – probably oldest drug used for euphorising effect (2500 BC
in graves of „Huaca Prieto“ – Inkas leaders
• Spanish conquistadors imported drug into Europe in 18th century, boom in
19th century, for example Vinum Marianum (Angelo Mariani)
• 1859 isolation of cocaine (Niemann), 1884 described local anesthetic and
vasoconstrict, used without knowledge of chemical structure
• 1888-1900 Willstätter elucidated structure
• 1905 willful change of structure → procaine
• 1955 Hardegger and Ott – absolute configuration
• Misused for euphorizing effect (lowering of noradrenaline, serotonin and
dopamin reuptake), increases muscular output, takes away feelings of
hunger
• Decompose in GIT, therefore i.v. application or snuffing, triggers strong
physical dependence
• According to literature 650 tons of cocaine per year, 2 % for medicinal
purposes
Usage: surface anesthesia in ophtalmology and ORL, stomatology
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MENTHOLUM RACEMICUM – RACEMIC MENTHOL (ČL 2005)
Menthol induces on the skin feelings
of cold via specific stimulation of
neural terminations for cold
perception.
Decreases mucosal secretion:
• weak anesthetic
• antipruriginose
Menthae piperitae folium (ČL 2002)
Menthae piperitae etheroleum (ČL
2002)
CH3
OH
CH3
OH
1
3
4
(1R,3R,4S)-3-p-menthanol (1S,3S,4R)-
přírodní
CARYOPHYLLI FLOS – clove flower (ČL 2005)
CARYOPHYLLI ETHEROLEUM – clove essential oil (ČL 2005)
EUGENOL
Source: Syzygium aromaticum –
clove (Myrtaceae); tree cultivated
in tropics
Drug: whole flower buds dried untill
obtain red-brown pigmentation.
Contain at least 150 ml of
essential oil / 1 kg of drug.
Obtained by distillation with
water steam.
CC: essential oil containing 70-85 %
of eugenol, 10 % of βcaryophylene,
aliphatic and
aromatic terpenoids
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CARYOPHYLLI FLOS – clove flower (ČL 2005)
CARYOPHYLLI ETHEROLEUM – clove essential oil (ČL 2005)
EUGENOL
Usage:
• topic preparation for treatment of
small wounds
• infection of oral cavity (oral
hygiene)
• spices
• Indonesia – cigarettes „KRETEK“
• cosmetics – Old Spice
EUGENOL
CARYOPHILLI ETHEROLEUM
In stomatology:
• local anesthetics
• desinficiens
OH
OMe
eugenol
4-allyl-2-methoxyfenol
NATURAL COMPOUNDS USED IN OPHTALMOLOGY
MIOTICS – narrowing pupil,
lowering intraoccular pressure,
increasing curvature of lens,
induce loss of accomadation
Usage: glaucoma
• Pilocarpinum chloridum
• Physostigminum salicylatum
• Galanthaminum bromatum
MYDRIATICS – expanding pupil,
increasing intraoccular pressure,
induce disorder of
accomodation
Usage: physical examination of eye
background, after post-surgical
adhesions
• Atropinium sulfuricum
• Homatropinium bromatum
LOCAL ANESTHETIC
• Cocainum hydrochloridum
Also mydriatic and
vasoconstringent
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PERIPHERAL MYORELAXANTS
CURARE
Curare – indian arrow poison with myorelaxant effect. Toxic only when
applied parenterally. Per os not-effective.
• used by Indians in firth of Amazon and Orinoco to hunt wild animals
• Thickened water extract from parts of Chondrodendron, Telito- xicum,
Anomospermum and Strychnos species.
• Previously classified according to package (charakteristic for certain
areas): tubo curare – in bambus tubes, pot curare – in earthen pots,
calebas curare – in fruits of bottle trees
In present time: division of curare according to botanic origin and chemical
constitution
Calebas curare in emptied fruits
Lagenaria vulgaris, L. siceraria and Crescentia cujete
Lagenaria vulgaris Lagenaria siceraria
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MENISPERMACEAE CURARE
Source: Chondrodendron tomentosum
(Menispermaceae). Climbing tropical wine
of Amazonian, Peruan, Columbian
rainforests
Drug: into solid consistence thickened water
extract from do pevné konzistence
zahuštěný vodní extrakt kořenů, kůry a
listů
OL: směs alkaloidů s převahou tubokurarinu.
Získá se isolací z vodného roztoku jako
pikrát, pro aplikaci se užívá chlorid.
Další zdroje: rostliny rodu Anomospermum,
Telitoxicum
TUBOCURARINII CHLORIDUM – TUBOKURARINIUM-CHLORID
(ČL 2005)
Použití:
• Svalové relaxans v hrudní a
břišní chirurgii při celkové
anesthesi
• K uvolnění spasticity svalů
• K uvolnění tetanických křečí
• Diagnostikum myasthenia
gravis
TUBARINE inj.
O
CH3
O
H
H
N
+ OH
O
OH
OMe
(CH3
)2
N
CH3
-
Cl
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LOGANIACEAE KURARE
Zdroj: Strychnos toxifera, S.
castelnaei, S. crevauxii – Kulčiba
jedovatá (Loganiaceae); stromy
Amazonie, Peru, Kolumbie
Droga: do pevné konzistence
zahuštěný vodní extrakt kůry a
listů
OL: deriváty bisindolových alkaloidů
typu strychninu: C-toxiferin,
C-kurarin
C-TOXIFERIN
ALCURONII CHLORIDUM – ALKURONIUMCHLORID (ČL 2005)
Použití:
• pro přípravu polosyntetického
ALKURONIUMCHLORIDU
(methyly kvarternizující dusíky
jsou nahrazeny allylem)
• Svalové relaxans v hrudní a
břišní chirurgii při celkové
anesthesi
• K uvolnění spasticity svalů
• K uvolnění tetanických křečí
ALLOFERIN inj.
N
N
+
CH2OH
H
CH
H
CH
CH3
H
N
H
N
+
CH3
HOH2
C
H
H
Cl
Cl
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