Copyright
Hugh McGuigan.

An introduction to chemical pharmacology: pharmacodynamics in relation to ... online

. (page 19 of 30)
Online LibraryHugh McGuiganAn introduction to chemical pharmacology: pharmacodynamics in relation to ... → online text (page 19 of 30)
Font size
QR-code for this ebook


When given subcutaneonsly the excretion is slower.



Day


Quinine given
daily


24-hour
urine, cc.


Quinine
recovered


Per
cent.


Second


0.605


1400
1700
1400
1450
1600
1500


0.108
0.120
0.083
0.128
0.076
0.071


17 9


Third


19 8


Fourth


13 7


Fifth


21.1


Sixth


12 6


Seventh


11 7







ASSAY OF THE ALKALOIDS IN CINCHONA BARK

The Calisaya bark is most easily worked and is crystallized
most readily by the Keller-Haubensack method: Put 12 grams
of calisaya bark in fine powder in a fiask and add 120 grams of
ether. Shake thoroughly and add 10 cc. ammonkt hydroxide —
10 per cent. NHs. Shake frequently during 30 minutes. Then
add 15 cc. water and shake thoroughly. Pour 100 grams of the
clear ether extract into another flask and add 40 cc. of 1 per cent,
sulphuric acid. Shake thoroughly and allow to settle. The acid
aqueous solution contains the alkaloidal sulphates. Pour off
most of the ether without losing any of the water solution.
Transfer the acid solution to a separatory funnel and make alka-
line with ammonium hydroxide (6 cc. 10 per cent, solution).
Extract with a mixture of yi ether and % chloroform, using about
40 cc. of the mixture. Separate this extract and transfer it to a
dry flask. Repeat the extraction with 20 cc. of the ethe^ chloro-
form mixture. Separate and transfer this also to the flask con-
taining the first extract. To get rid of the water filter through a
dry filter into a weighed dry flask and allow to evaporate. The



Digiti



zedbyGoOgte



ISOQUTNOHNE



261



alkaloids will crystallize out. After the solvent has evaporated,
weigh and calculate the percentage of alkaloids in the bark.

Tests for Quinine

A solution of quinine in sulphur, acetic or tartaric acids shows
a beautiful light blue fluorescence. The addition of a small
amount of these acids increases the fluorescence. Solutions of
the alkaloid in hydrochloric or hydrobromic acids are not
fluorescent. Salts diminish it. The fluorescence is best seen by
drawing the solution into a pipette.

Thalleioquine Test. — (Thallos — ^green) . To 10 cc. of a solution
of quinine bisulphate add a few drops of freshly prepared chlo-
rine or bromine water and an excess of ammonia. Stic. A
characteristic emerald green color develops. Urea, antipyrine
and caflFeine, interfere with this test. Morphine, pilocarpine,
cocaine, atropine, codeine, strychnine, phenol, and chloral have
no influence. It is very important that the chlorine or bromine
water be freshly prepared as the presence of HCl or HBr may
prevent the development of the color.

Isoquinoline Alkaloids. — The most important are papaverine,
hydrastine, narcotine, cotarnine, and berberine.

The formula of none of these is definitely established. Skele-
ton formulse for papaverine and berberine are:




CH2



— O.CH3



\O.CH3
Papaverine



Digiti



zed by Google



262



CHEMICAL PHARMACOLOGY



CH2



/
\



0—



o—




— O.CH,



\O.CH,
Berberine

They are of little importance in medicine and their fate in the
body is not well known.

Hydrastine and Hydrastinine. — These are isoquinoline alka^
loids prepared from the root of hydrastis canadensis. On decom-
position, hydrastine takes up water and hydrastinine and opianic
acid are produced:

C2iH2iNO« + H2O = CoHioOs + CuHiaN,
Hydrastine Opianic acid Hydrastinine

CHO



Opianic acid has the formula



COOH
OCH,



OCHs



Formulas assigned to hydrastinine and hydrastine are:



Digitized by



Google



HYDRASTINE



263



OCH3



CH






0— '



CHO
/\/ NH.CH3



0—



CH3O—



/\



Cfls



\/\y
CH2



Hydrastinine



-CO



\^'



.— CH



\







CH2:



0—



CH



o-



N.CH3



CH2



C.0H2

Hydrastine
Narcotine, an opium alkaloid, is methoxy hydrastinine and
yields opianic acid on hydrolysis. Hydrastinine has been synthe-
tized by Fritsch and its synthesis throws light on the structure of
hydrastinine. Hydrastinine increases the reflex irritability of
frogs leading to tetanus resembling that produced by strychnine,
and fi^nally to paralysis. In mammals the small amounts slow
the pulse; larger doses cause convulsions and tetanus. The
pulse is slowed by stimulation of the vagus center, and blood
pressure rises for the same reason. It also causes contraction of
the uterus. It is excreted unchanged in the urine.

Hydrastinine. — ^The hydrolysis of hydrastine changes its action
markedly. Hydrastinine causes but a small increase in blood
pressure. It has no convulsant action but instead is a central
depressant and does not weaken the heart, but stimulates it by
direct action. Its most important action is on the uterus — due to
a direct action on the muscle though there is some action through
the nerves.

Hydrastine Tests

1. Concentrated sulphuric acid dissolves hydrastine without
color imtil warmed when the solution becomes violet.

2. When dissolved in dilute sulphuric acid, and very dilute
potassium permanganate added, drop by drop, hydrastine is
converted into hydrastinine, and the solution shows a beautiful
blue fluorescence.

3. Froehde's reagent dissolves hydrastine with a rose red
changing to brown color.



Digiti



zed by Google



264 CHEMICiUi PHARMACOLOGY

4. Soluble chromates precipitate insoluble hydrastine chromate
which gives a fleeting red color with sulphuric acid.

htdrashnine

1. It crystallizes from light petroleunof in colorless glancing
needles which melt at 116^-117^0. ,

2. It is optically active.

3. It is soluble in alcohol, sparingly soluble in water, forming
yellow fluorescent solutions.

4. It forms salts with hydrochloric acid — which is the form of
the alkaloid used in medicine. The aqueous solutions show a
blue' fluorescence. Bromine water gives a yellow precipitate.

Narcotiiie. — Narcotine is an opium alkaloid; in composition
it is methoxy-hydrastine. It crystallizes from alcohol in color-
less needles which melt at 176**C. When hydrolyzed with dilute
acids it yields opianic acid and hydro-cotamine.

1. CnHzsNOT + H,0 = CioHioOfi + CwHi^NOt
Narcotine Opianic acid Hydro-cotamine.

2. With dilute HNOi narcotine gives opianic acid and co-
tarnine the constitution of which are

OCH,

I H

C C

HC C.OCH, CHaO-C CH

I II I II '

HC C.CO CHsO— C C— C = O



c



\/ H
C



HC— O . HO— C=0

I
CHaO.C CH

.0— C C N.CHs Opianic acid

H,C.0( I II I

^O— C C CH2

c c

H H2
Narcotine



Digitized by



Google



NARCOTINE 265

CH3O

I H2

c c

.0— C C N— CH3
H.C<^ I II I
^0— C C CH2

c c

H H2
Hydro-cotarnine

In action narcotine resembles morphine but is less hypnotic
and has some strychnine-like action though the hypnotic action
predominates (see page 256). Mphr states that in cats con-
vulsions precede tbe narcotic stage. It is but little used in thera-
peutics, although it has some antipyretic action.

Tests for Narcotine

1. The alkaloid dissolves in concentrated sulphuric acid with
a greenish color changing to reddish violet and after several days
to a raspberry red.

2. When narcotine is dissolved in concentrated sulphuric acid
and a trace of nitric acid added a red color is produced.

3. A solution of narcotine in sulphuric acid gives a blue color
on warming with gallic acid (Labat).

Cocaine is the alkaloid of coca leaves. It is a white crystal-
line^ solid that melts at 98**C. The hydrochloride is the most
important salt. The formula of cocaine is.

H2C CH HC— COOCHa

It

N— CH3 CH— OOC— CeHs

I I

jjC CH — ' CH2

Cocaine or methyl benzoyl ecgonine

On hydrolysis cocaine gives methyl alcohol, benzoic acid and
ecgonine:



Digiti



zed by Google



266 CHEMICAL PHARMACOLOGY



CHj CH CH.COOH

H
N.CHa



K



CH2 CH CH2

Ecgonine

Cocaine can be prepared from ecgonine by benzoylation and
methylation; and ecgonine has been synthetically prepared from
tropine, but so far the synthetic product has not been separated
into its optical isomers. The natural product like most natural
alkaloids is levorotatory. A dextrotatory (isococaine) isomeride
of 1. cocaine has been prepared from coca leaves, but this is now
thought to be formed from the 1. cocaine by the action of alkaUes.
L. cinnamyl cocaine C19H23O4N is the chief alkaloid of the
Java cocoa leaves. The d. isomeride does not occur in the coca
leaves but has been prepared synthetically.

Action of Cocaine

The chief action of cocaine is its local anesthetic effect. This
is due to its general protoplasm action, though it acts more
strongly on the sensory nerves than on motor ends. The effect
is due to the benzoyl group. Large doses first stimulate, then
paralyze the central nervous system, chiefly in a descending di-
rection. The heart muscle is directly stimulated by small doses
and paralyzed by larger doses. The striated muscles are also
stimulated by a direct action. There is a marked mydriasis,
formerly thought to be due to stimulation of the sympathetics
locally, but later work questions this location. The toxic dose
of cocaine varies enormously. Swabbing the tonsils with 4
per cent, has proved fatal in some cases while over 1.5 grams have
been taken per os with recovery.

The Fate of Cocaine in the Body

Neither man nor dog eliminates in the urine more than 5 per
cent, of the cocaine ingested, and since the urine contains no
ecgonine it is thought to be profoundly changed in the organism.
In the oxidation in the body it is thought to be first decomposed
into ecgonine, benzoic acid and methyl alcohol, and these are



Digiti



zed by Google



NARCOTINE 267

then oxidized. Proells could not detect cocaine in cadaveric
material after 14 days.

ARTIFICIAL COCAINES

A large number of artificial cocaines have been prepared. All
these contain a benzoyl radical. The most important artificial
cocaines are:

Anesthesine, or para amino ethyl benzoic acid:
NH2C >-C0.0 C2H



2<^ N— CO.O



2X1 6



Pro-cocaine or novocaine is the hydrochloride of the diethylamine
derivative of anesthesine or para amino benzoyl di-ethyl amino
ethanol and has the formula.



NH < >CO.O.CH2CH2N(C2H5)2HCl



A number of other substitutes have been prepared.

Tests for Cocaine

1. Heat a few milligrams of cocaine with a few drops of alco-
hol and concentrated H2SO4. Note the odor of ethyl benzoate.

CcHbCOOH + C2H5OH = CeHfiCOOCaHB + H2O

2. Boil a solution of cocaine with a drop of H2SO4 and add a
drop of FeaCle. Ferric benzoate is precipitated.

3. Physiological tests: Local anesthesia and dilation of the
pupil, when applied locally.

THE PYRROL OR PYRROLIDINE GROUP OF ALKALOIDS

1. This includes, in addition to pyrrol and pyrrolidine, hygrine,
a derivative of n. methyl pyrroUdine :

CH2.CH -CO.CH2.CH8

Nn.CHs
CH2 CH2
and kuskhygrine from the leaves of erythroxylon coca.



Digiti



zed by Google



268



CHEMICAL PHARBfACOLOGY



2. Stachydrine from • stachys tuberifera has the formula.
CH, CH2



CO CH CH,

N(CH3)2



which is .a dimethyl betaine of pyrrolidine.

The atropine and cocaine group of alkaloids may be considered
in this group or in the tropane group. They may be regarded
as a combination of a piperidine and a pyrrolidine nucleus, which
is tropane

CH a Cx i C112




CH2-



Tropane
Pyrrol— (pyros, fire-oL, oil) is a constituent of coal tar, and a
product of the distillation of bones. It has the formula: C4HJN
or

CH CH



CH CH

\/
NH

It is more toxic than p3rridine or piperidine. It resembles
benzene in action.

Blood coloring matter, chlorophyll and protein decomposition
products contain a pyrrol nucleus. The derivatives of pyrrol are
classified according to the scheme



1/2
NH



or



fi'



fi



NH



Digit!



zed by Google



NARCOTINE



269



On reduction with hydriodic acid and phosphorus, pyrrol
yields pyrrolidine:

Cri2 CBL2

1 I

dl2 0x12

NH

which is a much stronger base than pyrrol.

Pyrrol has been synthesized in several ways. It has been
formed by the interaction of succin-dialdehyde and ammonia:

,0H



CH,



CH,



-C/ +NHa
^0



CH2.CH:



\



NH2






H



+ NH3 CH2.CH



O






NHs



CH = CH

I .

CH = CH



\



./•



NH + NH, + 2H2O



Pyrrolidine has also been formed by heating penta-methylene
diamine with hydrochloric acid.



CHj'



CH2 CH2NH



CH,



NH.



H



+ HCl



H



N



c-



-CHs



H2C CH, + NH4CI

\y

NH

Pictet (Ber. deut. chem. Gesells, 1907, 40, 3771) thinks that alka-
loids in plants are formed by the breaking down of complex nitro-
genous substances, such as protein and chlorophyll, and by a
condensation of these substances with others, as in the syntheses
above. He is of the opinion that methylation within the plant
can be accomplished by the action of formaldehyde on amino or
hydroxyl groups:

ROH + CH2O = RO CH3 +
or RNH2 + CHjO = RNHCHs +



Digitized by



Google



270



CHEMICAL PHARMACOLOGY



It should be noted that methylation in the animal body is of rare
occurrence (see p. 249). Various alkaloids may then be formed
by other changes, for example, by heat. The secretion of alka-
loids by plants may, according to Pictet, be a means of getting
rid of nitrogen which cannot be used in metabolism. It is a
curious fact that these alkaloids, though highly toxic to animals,
are not toxic to the plants themselves. The theory that alkaloids
are necessary compounds in the plant and are secreted to protect
the plant from animals does not agree with the fact that plants
grow just as well when moved into other latitudes, yet the content
of alkaloid is much diminished.

Methyl pyrrol can be changed to pyridine by heat:



N.CH3 N Pyridine.

Fate of Pyrrol in the Body

Pyrrol and its derivatives appear to be easily destroyed in the
body.

TROPINE ALKALOroS WITH DIHETERO CYCLIC NUCLEI
Tropane Alkaloid. — Tropane has the formula:

Cri2 CH CH2

/ \

NCH3 CH2

\ /



CH2-



-CH-



-CH2



This substance contains a piperidine ring and a pyrrolidine
ring, consequently there may be some duplication in the classi-
fication. The tropane alkaloids would include:

I. The atropine group — atropine, hyoscine, hyoscyamine.
II. The cocaine alkaloids — cocaine and tropo cocaine.
III. The pomegranate alfeftloidg — pelletierine, isopelletierine,
etc., from punica gr^iiatum,



Digiti



zed by Google



ATROPINE 271

IV. Cytisine from cytisus laburnum, lupinine irom lupinus-
luteus and niger, etc.

Tropine differs from tropane in that one of the H. ions of tro-
pane is replaced by hydroxy!:

H2C CH CH2

1 I /CH2OH

NCH, CHOH + CeHs-CH/

1 I ^COOH

H2C CH — CH2

Tropine Tropic acid

Atropine is a combination of tropic acid and tropine. When
other acids are used tropeines are formed.

Atropine :

CH2 CH — '■ CH2

I I /H /CH2OH

CH 2 CH CH2

The main actions of atropine are stimulation of the central nerv-
ous system and paralysis of the peripheral para sympathetic
nerve endings. In these actions the tropine part of the ester
is the more important. This is proved by the fact that other
acids may be substituted for tropic acid. The only other acid
that has yielded an ester of practical importance is mandelic
acid, which is

Homatropine, C6H7N(CN8)C2H40.CO.CHOH.C«H6

The action of homatropine is practically the same as atropine
but it is less toxic. It is used especially in eye work, since the
dilation of the pupil caused by it lasts only a few hours,
while that caused by atropine may last for days.

The tropines derived from benzoic and cinnamic acids exert
no mydriatic action.

The Fate of Atropine in the Body

Atropine is readily absorbed and excreted. After adminis-
tration it has been found in most all tissues and fluids. It has



Digiti



zed by Google



272 CHEMICAL PHARMACOLOGY

been found in the milk and in the foetal blood. It is decomposed
to tropine and oxidized in the body, though some may escape
imchanged in the urine. It is very resistant to putrefaction and
has been found in bodies after two years.

Tests for Atropine

1. Boil a small amount with dilute H2SO4. This gives an
orange flower odor which changes to that of bitter almond. The
solution gives a green color when a trace of potassiiun bichro-
mate is added.

2. To a trace of atropine in a test tube add 10 drops of H9SO4
and heat until it becomes brown or imtil white fumes appear.
Then add 2 voliunes of water. During the heating there will be
a sweetish odor resembling tuberose, which is characteristic
(Gulichno). The odor is strengthened by adding a little KMn04
(Reuss). This test is sensitive to 10 milligrams.

3. Vitali's Test. — Put 1 or 2 mgms. of atropine in an evaporating
dish and dissolve in it a few drops of fuming nitric acid and
evaporate to dryness high above the flame or on a water bath;
cool and touch the spot with a drop of alcoholic solution
of KOH. The color will be violet, changing to cherry red. Vera-
trine also gives this test, hence it is characteristic only in the ab-
sence of veratrine.

4. Atropine dilates the pupil and gives a dry sensation to the
mouth and eliminates vagus action on the heart, thus causing a
very rapid rate of heart. These tests can be recognized with
certainty in presence of veratrine.

Scopolamine or Hyoscine, C17H21O4N, is a tropane alkaloid
whose composition is so closely allied to atropine and hyoscya-
mine that the same reactions are given. With mercuric chloride
atropine gives a yellowish red precipitate of mercuric oxide,
while hyoscyamine gives a white precipitate.

When warmed with barimn hydroxide, scopolamine is hydro-
lyzed yielding tropic acid and a base C2H18O2N — named
pseudo-atropine, oscine, oxytropine or scopoline,

Hyoscine resembles atropine in its action on the nerve termi-
nals, but has practically no action in stimulating the central
nervous system. The main action is a feeling of fatigue and
drowsiness. It has been often used to produce ''twilight sleep."



Digiti



zed by Google



GLYOXALINE ' 275

THE GLYOXALINE GROUP OF ALKALOIDS

This includes pilocarpine, isopilocarpine and jaborine, which
may be a mixture of pilocarpine and isopilocarpine. There are
other- unimportant members such as pUocarpidine. The only
one of interest in medicine is pilocarpine.

Glyoxaline is metameric with pyrazole and may be regarded
as a pyrrol nucleus in which one methine radical has been replaced
by nitrogen. It is formed when ammonia acts on glyoxal in
presence of formaldehyde; sufficient formaldehyde may be
formed from the glyoxal without the extra addition of it.
CHO NH, CH— N ^
I + +0:CH2-^|| ^CH + SHjO

CHO NHs CH— NH^
Glyoxaline
The piu'ine group of alkaloids contain a glyoxaline nucleus and
may be regarded as a glyoxaline ring condensed with pyrimidine.
'2 GH N 1

/ \

3 N CH 6

\ /

4 C C 5

I I

9 N NH 7

^ CH /
8
• Glyoxaline may also be prepared by oxidizing benzimidazole
with permanganate.



— N V H COOH.C— N ^

J)CH-^ II ^CH

— NH^ H COOH.C- NH^



Glyoxaline dicarboxylic acid

H. C>-N .

II ^CH + 2C0a

H. C— NH^

Glyoxaline
Compare with the given formula for purine, p. 283.



18



Digiti



zed by Google



"274 CHEMICAL PHABMACOLOGY

Pilocarpine is a colorless oil, freely soluble in water, alcohol and
chloroform and but slightly soluble in ether and light petroleum.
It readily forms crystalline salts with acids and the nitrate is the
most important. It is readily soluble in water. The alkaloid of
commerce is derived from the leaves of pilocarpus jaborandi, a
South American plant. It has been prepared synthetically, and
based on this synthesis Jowett and Piiiner consider pilocarpine

C2H6— CH— CH— CH2— C N— CHs

to have the formula I

CO CH2 CH CH

N

Iso-pilocarpine is probably a stereoisomeride.

Action of Pilocarpine

Pilocarpine is a strong stimulant to all glands, especially the
sweat, salivary, bronchial, lachrymal, gastric, and intestinal.
The smooth muscles of the alimentary tract, the urinary bladder,
spleen and bronchi are stimulated . The muscles of the blood
vessels are not influenced, but when given intravenously the
heart is slowed by an action on the vagus endings. When taken
by mouth, the heart rate may be increased. This action has not
been satisfactorily explained; it may be secondary. There is
some stimulation of the central nervous system, followed by
paralysis after large doses. The whole action of pilocarpine,
resembles that of muscarine, but it is much less poisonous.

Pilocarpine is used in medicine almost totally for its diaphoretic
action, especially in cases of dropsy and similar diseases. Iso-
pilocarpine and pilocarpine have a similar but weaker action.
Pilocarpic acid is inactive. Very large or toxic doses of pilocar-
pine cause profuse sweating, flow of nasal secretion, tears, pallor,
slow heart, and arrythmias, vomiting, diarrhoea, contracted
pupil, tremors, cloudiness of the cornea, tracheal rdles, and edema
of the lungs. The part played by the glyoxaline ring has not
been determined.

Atropine is antidotal in all cases and a small dose will neutralize
the effects of a large dose of pilocarpine.



Digiti



zed by Google



PHENANTHRENE GROUP 275

Fate in the Body

A large part is excreted unchanged in the urine. There may
be. some in combination (Curci).

Tests for Pilocarpine

1. The general alkaloidal reagents especially delicate for
pilocarpine are iodo-potassium-iodide, phosphomolybdic acid, and
phospho tungstic acid.
. 2. Pilocarpine nitrate melts at 176°-178°.

3. A solution of pilocarpine in formalin sulphuric acid when
warmed becomes yellow-brown-red.

4. In a test tube add a crystal of potassium bichromate to 2 cc.
chloroform with pilocarpine and 1 cc. hydrogen peroxide; shake.
Depending on the amount of pilocarpine the chloroform is blue
violet, dark or indigo blue.

6. Physiological tests: These are constriction ojf the pupil,
slowing of the heart, profuse sweating and an edematous con-
dition of the lungs.

PHENANTHRENE ALEiALOIDS

Phenanthrene is an isomer of anthracene and occurs with it in
coal tar.



Phenanthrene




Phenanthraquinone


4 3/ \2

\ / \
6 7 8


1
">10
~9


CO CO

/ \
/ \ / \
\ / \ /



Phenanthrene Group.— The most important representatives
of the group are morphine, codeine, thebaine, and apomorphine.
On distillation with zinc dust these alkaloids yield pyrrol,
pyridine, quinoline, and phenanthrene; consequently, they may
be placed under either of these headings.

Phenanthraquinone is obtained from phenanthrene by oxida-
tion with glacial acetic and chromic acids. According to Amoss,
morphine is a derivative of tetrahydro-dioxy phenanthrene to
which- a morphoUne is added. To morpholine he assigned the
formula:



Digiti



zed by Google



276



CHEMICAL PHARMACOLOGY







CH»
CH,







and to morphine
OH.



NH
Morpholine



OH



CH2



\



C14H



10



CH,
CH,



N



/■ \/ \

CH-



CH,
Morphine



-N— CH,

I
CH,



CH30\ /\ /\ ,

\/ \/ \y

I CH

CHs

/
C CH2

\/

CH.OH
Codeine (Knorr)
CHj

/ x/- \

CH N— CHs /^

! I HoA

I CH2 HO



CH30\ /\ /\ /

\/ \y \/

CH /
I CH2



\^\



CHs



0-



-C



/



/\^\



\ /•

COCH,
Thebaine (Knorr)



dl2C/Xl2

Apomorphine



N— CH,
CH2



Digiti



zed by Google



THEBAINE



277



CH, N— CH,

CH CH,

I
CH

C— H

I •
0— C CHa

H C

V\
H OH

Codeine (Pschoir)



CH, N— CH,

CH CH,

I
CH,

CH,0\/\/\/

C— H

I
— C CH

H C

I
OCH,

Thebaine (Pschorr)



Roser and Howard (Berichte, 1886, 19, 1596) think the re-
lationship of morphine, codeine and thebaine may be shown as
follows:



HO.
HO^



CHsO



CiiJIuONCH,



OH



\



CwHuONCH,



Morphine



Codeine



CHaO



CH,0



CHiiNO.CHa



Thebaine



In accordance with this view it has been found that the prin-
cipal decomposition products of all three are similar. Codeine
is methyl morphine. The graphic formulas are now known
with certainty, but among others the foUowing have been pro-
posed for morphine:



Digit!



zed by Google



278



CHEMICAL PHAEMACOLOGY



CH2

CH N— CHs



HO



CH2



\ /\ /\ /



\/



H






o-



/



CH2

/

C CH2

\/

c

/\

H OH
Knorr's later formula



CHa N— CH,

CH CH2

I

CH2
H0\/\^\/

C— H

I
0— C CH2

H C

/\
H OH

Pschorr's formula



CH2



HO



CH



I CH



CH2-
H



-N



1 CHa
CH CH2

\ /

C
/\
/ \
H OH

Bucherer's formula modified by Knorj



Digit!



zed by Google



APOMORPHINE 279

The principal pharmacological actions of morphine are:



Online LibraryHugh McGuiganAn introduction to chemical pharmacology: pharmacodynamics in relation to ... → online text (page 19 of 30)