CENTRAL ANALEPTICS
1. Stimulating effect on CNS
2. Stimulating respiration and blood circulation
3. Higher doses – convulsions of central origin
Therapeutic usage possess mainly methylderivatives of xanthine
(purine bases)
Other drugs/compounds usage is limited, because after stimulation
usually comes suppression
Chemically heterogeneous group
N
N N
H
N N
N N
N
H
NH
N
H
N
N
H
O
O
N
N
N
H
O
O
N
CH3
CH3
NH
N
N
O
O
N
CH3
CH3
N
N
N
O
O
N
CH3
CH3
CH3
pyrimidine imidazol purine xanthine
1
2
3
4
5
6
7
8
9
1
3
7
1
3
theophyline
3
7 1
3
7
theobromine caffeine
METHYLDERIVATIVES OF XANTHINE –
PURINE BASES
N
N N
N
R2
O
R1
O R3
xanthine R1 = R2 = R3 = H
caffeine R1 = R2 = R3 = CH3
theophyline R1 = R2 = CH3, R3 = H
theobromine R1 = H, R2 = R3 = CH3
Theophyllinum - Theophyline (ČL 2005)
Theobrominum - Theobromine (ČL 2005)
Coffeinum - caffeine (ČL 2005)
RELATIVE PHARMACOLOGIC EFFECT OF XANTHINE
DERIVATIVES
Effect caffeine theobromine theophyline
Stimulation of CNS +++ ± +
(cortex and subcortex)
Stimulation of skeletal muscles ++ ± +
Stimulation of heart muscle + ++ +++
Dilatation of coronary veins ± + ++
Relaxation of bronchial muscles + ++ +++
Stimulation of gastric secretion ++ ± ±
Diuretic effect + ++ +++
DRUGS CONTAINING METHYLDERIVATIVES OF
XANTHINE
Coffeae semen – coffea seeds
Theae folium – Tea leaves
Colae semen – Cala seeds (ČL 2005)
Cacao semen – Cacao seeds
Mate folium – maté leaves (yerba maté)
Guarana (Pasta guarana) - Guarana
Coffae semen – Coffea seeds
Source: Coffea arabica – Arabica coffee, C.
liberica – K. liberijský, C. canephora var.
robusta – K. mohutný and other species
(Rubiaceae)
Evergreen shrubs or small trees
Fruit is egg-shaped double-capsuled drupe
with diameter approx. 1,5 cm
Producents: Brazil, Columbia, Mexico,
Guatemala, Ivory Cost, Ethiopia,
Indonesia, India, countries of Arabic
peninsula
Drug: seed with removed pericarpium and
testa, roasted at 200-250 0C
CC: 0,4-2,5 % of caffeine, traces of
theobromine and theophyline, 2-5 % of
chlorogenic acid. During roasting are
produced other artifact compounds.
Usage: for caffeine isolation, febrile states
during infectious diseases, alcohol
intoxication. Beverages.
THEAE FOLIUM – TEA LEAVES
Source: Thea sinensis – tea plant (Theaceae).
Cultivated, perennial, up to 2 m tall shrub, know in
many varieties.
Main producers: China, Kenya, Turkey, Vietnam, India,
Ceylon, Japan, Indonesia.
Harvest of terminal leaves from 3-years and older
plants. Younger leaves are preferred for quality of
essential oils and caffeine content. From one plant
cca 250 g of fresh leaves can be obtained.
Treatment: Green tea (China, Japan), black tea (India,
Ceylon)
Drug: dried leaves after fermentation
CC: 1,5 to 4,5 % of caffeine (according to species and
manufacturing process); 0,04 % of theobromine
and theophyline; 10-25 % of catechine tannins
(hybrids of hydrolysable and condensed tannins);
0,5-1 % of essential oil (250 components) mainly
moterpenic aldehydes and alcohols, flavonoids
Usage: tea infusion – mild astringent, antidiarrhoic,
cosmetic, concentrated decoction – antidote for
heavy metals, proteins and alkaloids intoxications
Residues of tea harvest – for caffeine isolation.
Beverages.
THEAE FOLIUM – TEA LEAVES- HARVEST
COLAE SEMEN – KOLA NUTS (ČL 2005)
Source: Cola nitida – kola tree, C. acuminata – K.
zašpičatělá (Sterculiaceae)
Trees native to tropic Africa, cultivated in Brazil, at
Jamaica, Java, Madagascar, in Cameroon and
Togo
Fruit is a capsule containing 3-6 seeds
Drug: from rippen fruits obtained and sun-dried
seminal germ
CC: 1-3 % of caffeine, 0,1-0,2 % of theobromine,
partially linked-up with tannins – so called
colateins; 3-5 % of catechine tannins (produced
during drying process, starch, fat
Usage: galenic preparations with psychostimulation
and diuretic effects
Beverages.
Coca-Cola contain cca 20 mg of caffeine in 100 ml
Coca-Cola – 1886 PhMr. Pemberton and Asa
Chandler
CACAO SEMEN – COCOA BEANS
Source: Theobroma cacao – cacao tree
(Sterculiaceae)
Caulifloral tree native to tropic Middle and South
America; important part of tropical agriculture
(Brazil, Ghana, Niger)
Fruits are capsules containing 25-30 seeds in five
lines
Seeds are sun-fermentated (splitting of bitter
substances, formation of fragrant compounds
and dark pigmentation. After that follows
roasting at 100-140 0C, which gives typical
odor and smell
Drug: fermentated and roasted germ, resp. its
cotyledons
CC: 1-2 % of theobromine, 0,05-0,2 % of caffeine,
cca 50 % of fat, cca 5 % of tannins and starch
Grinding between hot rollers – cacao mass,
hydraulic pressing – Oleum cacao, residue is
cacao powder
Usage: testa for theobromine isolation; cacao
powder – snacks; Oleum cacao – additive,
chocolate manufacturing
CACAO SEMEN – COCOA BEANS
MATÉ FOLIUM – MATE LEAVES
Source: Ilex paraguariensis – yerba mate
(Aquifoliaceae). Tree native in South
America, cultivated. Main producer Argentina
Drug: bright-green skinny glossy leaves.
Inactivation of enzymes – branches are drag
out through flames without smoke – this
makes their special odor. Than dried in
driers.
CC: 1-1,5 % of caffeine, 0,05-0,3 % of
theobromine; cca 12 % of chlorogenic acid,
essential oil, flavonoids
Usage: Preparation of beverages with
psychostimulating effects. For European
people often too acrid and too „smoked“
GUARANA – PASTA GUARANA
Source: Paullinia cupana – guarana
(Sapindaceae). Climbing wine from
Brazilian and Venezuelan rain forests.
For usage is cultivated. Fruit is capsule.
Seeds are after harvest dried and
roasted.
Drug: roasted grinded seeds formed (water
+ starch) sticks.
CC: caffeine cca 5 %, catechine tannins to
25 %, starch, fat
Usage: Stimulant and admixture to
analgesic mixtures. In Europe used not
so often, more at America to prepare
refreshing beverages.
CAMPHORA D – D-CAMPHOR (ČL 2002)
CAMPHORA NATURALIS – NATURAL CAMPHOR
SOURCE: Cinnamomum camphora –
camphor laurel (Lauraceae). Burly
tree, evergreen, native at east
Asian coastal area. Cultivated in
other tropic and subtropic countries
(Florida, East Africa). For camphor
production are used trees at least
50 years old, camphor is obtained
by steam distillation.
Usage: Central analeptic in form of
intramuscular injections (obsolete
now)
Externally derivans, antipruriginose
Production of celluloid and smokeless
powder O
O
PICROTOXINE
Source: Anamirta cocculus –
fishberry (Menispermaceae);
climbing wine native to India
and Malaysia.
Drug: fruits – drupes Ø 1 cm
CC: to 1,5 % of picrotoxine
Effect: Potent central analeptic, it
is not used in clinics because
of narrow therapeutic
window.
Used for water poaching – fishes
convulsively swallow air
O
O
O OH
CH3
O
C
CH3 CH2
2
3
4
5
1
LOBELINE
Source: Lobelia inflata – indian
tobacco (Lobeliaceae). Biennial
plant native to North America.
In Europe cultivated.
Drug: Herb cut and dried in
flowering period.
CC: 0,2-1 % of piperidine
alkaloids; important is lobeline
and isolobinine.
Usage: Stimulant of respiratory
center (today obsolete);
component of antiasthmatic
preparations (isolobinin
triggers reflectoric bronchial
secretion at mucose and
support expectoration)
R1
N
R2
R3
CH3
lobeline, R1=O, R2=H,OH, R3=C6H5
isolobinine, R1=O, R2=H,OH, R3=C2H5
STRYCHNINE
Source: Strychnos nux vomica – nux
vomica (Loganiaceae); tree or
shrub native to tropic India, Ceylon
and northern areas of Australia;
cultivated in Cameroon, Cambodia.
Fruit = berry of apple size, inside
4-5 seeds.
Drug: flatt seed, on the margin
thickened, Ø 15-25 mm, rich in
presence of surface trichomes.
CC: 2,5-4 % of indol alkaloids, 90 % of
strychnine and brucine. Oil,
loganine.
Usage: For isolation of strychnine and
brucine and for preparation of
Strychni tinctura – syn. Nucis
vomicae tct.
• To treat perception disorders
• myopathic insufficiency of vocal
cords
• atonia of GIT
• amare (bitter taste)
N
O
H
O
H
H H
NH