Transcript Isoquinoline Alkaloids

Isoquinoline Alkaloids
Opium Alkaloids
• Many alkaloids have been identified in opium latex
(opiates) - maybe as many as 50.
• Morphine and codeine are the most important
Morphine first alkaloid identified from any plant in
1806 and the pain relieving properties soon
recognized
• Morphine (like raw opium) is strongly addictive
and because of this its general medical use
declined in 20th century
• Still drug of choice for cases of severe pain
Opium Poppy: Papaver somniferum
• Member of the Papaveraceae, poppy family
• Large showy annual with conspicuous flowers
(white, pink, red, purple)
• Fruit is a capsule that produces latex with
several potent alkaloids
• Latex is collected from cut capsules (latex
oozes out and dries – dried latex scraped off) dried latex called opium
Fresh capsule of opium poppy
Cut capsule showing latex exuding from cut
Morphine
HO- Group is needed for activity
2
HO
3
1
11
4
O
13
5
HO
10
15
12
9
14
H
8
6
16
H
N
CH3
7
Morphine (Astramorph)
HO- Group not important to activity
Morphine is primarily used to treat both acute and chronic severe pain. It is also
used for pain due to myocardial infarction and for labor pains. There are however
concerns that morphine may increase mortality in the setting of non ST elevation
myocardial infarction. Morphine has also traditionally been used in the treatment
of acute pulmonary edema. A 2006 review however found little evidence to
support this practice.
Immediate release morphine is beneficial in reducing the symptom of acute
shortness of breath due to both cancer and non-cancer causes. In the setting of
breathlessness at rest or on minimal exertion from conditions such as advanced
cancer or end-stage cardio-respiratory diseases, regular, low-dose sustained
release morphine significantly reduces breathlessness safely, with its benefits
maintained over time.
Its duration of analgesia is about 3–4 hours when administered via the
intravenous, subcutaneous, or intramuscular route and 3–6 hours when given by
mouth. Morphine is also used in slow release formulations for opiate substitution
therapy (OST) in Austria, Bulgaria, and Slovenia, for addicts who cannot tolerate
the side effects of using either methadone or buprenorphine, or for addicts who
are "not held" by buprenorphine or methadone. It is used for OST in many parts
of Europe although on a limited basis
Codeine
Codeine or 3-methylmorphine (a naturally occurring methylated
morphine) is an opiate used for its analgesic, antitussive,
antidiarrheal, antihypertensive, anxiolytic, antidepressant,
sedative and hypnotic properties. It is also used to suppress
premature labor contractions, myocardial infarction, and has many
other potential and indicated uses. It is often sold as a salt in the
form of either codeine sulfate or codeine phosphate in the United
States and Canada; codeine hydrochloride is more common
worldwide and the citrate, hydroiodide, hydrobromide, tartrate,
and other salts are also seen.
Codeine is the second-most predominant alkaloid in opium, at up
to three percent. Although codeine can be extracted from natural
sources, a semi-synthetic process is the primary source of codeine
for pharmaceutical use. It is considered the prototype of the weak
to
midrange
opioids
(tramadol,
dextropropoxyphene,
dihydrocodeine, hydrocodone, oxycodone).
Heroin
diacetylmorphine or morphine diacetate, also known as
diamorphine
Heroin is an opioid analgesic originally synthesized by C.R. Alder Wright in 1874
by adding two acetyl groups to the molecule morphine, which is found
naturally in the opium poppy. It is the 3,6-diacetyl ester of morphine. Heroin
itself is an inactive drug, but when inserted into the body, it converts into
morphine.
Illicit (‫ (غير مشروع‬heroin is sometimes available in freebase form. Because of its
lower boiling point, the freebase form of heroin is also smokable. It is prevalent
in heroin coming from Afghanistan, which in 2004 produced roughly 87% of the
world supply in illicit raw opium. However, the production rate in Mexico has
risen sixfold from 2007 to 2011, changing that percentage and placing Mexico
as the second largest opium producer in the world.
As with other opioids, diacetylmorphine is used as both an analgesic and a
recreational drug. Frequent and regular administration is associated with
tolerance and physical dependence. Internationally, diacetylmorphine is
controlled under Schedules I and IV of the Single Convention on Narcotic Drugs.
It is illegal to manufacture, possess, or sell diacetylmorphine without a license
in almost every country, except the UK and Switzerland
Other Isoquinoline Alkaloids
Emetine
Emetine
Emetine is a drug used as both an anti-protozoal and to
induce vomiting. It is produced from the ipecac root.
Early use of emetine was in the form of oral administration of the
extract of ipecac root, or ipecacuanha. This extract was
originally thought to contain only one alkaloid, emetine, but
was found to contain several, including cephaeline,
psychotrine and others. Although this therapy was reportedly
successful, the extract caused vomiting in many patients which
reduced its utility. In some cases, it was given with opioids to
reduce nausea. Other suggestions to reduce nausea involved
coating the drug to allow it to be released after digestion in
the stomach.
Test for emetine
Mix 0.5g powdered herb with 20ml HCL and 5ml
water.
Filter
To 2ml filtrate add 0.01g potassium chlorate
Result: if emetine is present, a yellow colour
appears. After standing for 1hr, changes to
red
Carapichea Ipecacuanha
Carapichea ipecacuanha is a flowering plant native to Brazil.
Traditionally its roots were used to make a powerful emetic to
induce vomiting at times of poisoning. Until recent times, it was
still used within hospitals and homes for this purpose
Berberine
Berberine is a quaternary ammonium salt from the protoberberine
group of isoquinoline alkaloids. It is found in such plants as Berberis [e.g.
Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry),
Berberis aristata (tree turmeric)], Hydrastis canadensis (goldenseal),
Xanthorhiza simplicissima (yellowroot), Phellodendron amurense (Amur
cork tree), Coptis chinensis (Chinese goldthread or Huang Lian Su),
Tinospora cordifolia, Argemone mexicana (prickly poppy), and
Eschscholzia californica (Californian poppy). Berberine is usually found
in the roots, rhizomes, stems, and bark. Due to Berberine's strong
yellow color, Berberis species were used to dye wool, leather and wood.
Wool is still today dyed with berberine in northern India. Under
ultraviolet light, berberine shows a strong yellow fluorescence, so it is
used in histology for staining heparin in mast cells. As a natural dye,
berberine has a colour index of 75160. As a traditional medicine or
dietary supplement, berberine has shown some activity against fungal
infections, Candida albicans, yeast, parasites, and bacterial/viral
infections. Berberine seems to exert synergistic effects with
fluconazole even in drug-resistant C. albicans infections
Berberidaceae (Berberis aquifolium(
Physostigmine ( Eserine) Uses
• Physostigmine is used to treat glaucoma, Alzheimer's
disease, and delayed gastric emptying. It has been
shown to improve short term memory. Recently, it has
begun to be used in the treatment of orthostatic
hypotension.
• Because it is a tertiary amine, it can cross the blood–
brain barrier, and physostigmine salicylate is used to
treat the central nervous system effects of atropine,
scopolamine, and other anticholinergic drug overdoses.
• Physostigmine is the antidote of choice for Datura
stramonium poisoning. It is also an antidote for Atropa
belladonna poisoning, the same as for atropine.
Calabar bean
The Calabar bean is the seed of a leguminous plant, Physostigma
venenosum, a native of tropical Africa, poisonous to humans. It
derives the first part of its scientific name from a curious beak-like
appendage at the end of the stigma, in the centre of the flower;
this appendage, though solid, was supposed to be hollow.
Strychnos nux-vomica
• The strychnine tree (Strychnos nux-vomica L.) also known as nux
vomica, poison nut, and quaker buttons, is a deciduous tree native
to India, and southeast Asia. It is a medium-sized tree in the family
Loganiaceae that grows in open habitats. Its leaves are ovate and 2–
3.5 inches (5.1–8.9 cm) in size.
• It is a major source of the highly poisonous, intensely bitter alkaloids
strychnine and brucine, derived from the seeds inside the tree's
round, green to orange fruit. The seeds contain approximately 1.5%
strychnine, and the dried blossoms contain 1.0%. However, the tree's
bark also contains brucine and other poisonous compounds.
• The use of strychnine is highly regulated in many countries, and is
mostly used in baits to kill feral mammals, including wild dogs, foxes,
and rodents. Most accidental poisoning is by breathing in the powder
or by absorption through the skin
Rauwolfia serpentina
(Catharanthus roseus( Vinca
‫معجل للوالدة‬
‫الشقيقة‬
Rye)‫(ألجاودر‬
• Rye (Secale cereale) is a grass grown extensively as a
grain, a cover crop and as a forage crop. It is a member
of the wheat tribe (Triticeae) and is closely related to
barley (Hordeum) and wheat (Triticum). Rye grain is
used for flour, rye bread, rye beer, crisp bread, some
whiskeys, some vodkas, and animal fodder. It can also
be eaten whole, either as boiled rye berries, or by
being rolled, similar to rolled oats.
• Rye is a cereal grain and should not be confused with
ryegrass, which is used for lawns, pasture, and hay for
livestock
Rye