Hung Kay LEE Department of Chemistry The Chinese University of Hong Kong The Chemistry of Some...
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Transcript of Hung Kay LEE Department of Chemistry The Chinese University of Hong Kong The Chemistry of Some...
Hung Kay LEEHung Kay LEE
Department of ChemistryDepartment of Chemistry
The Chinese University of Hong KongThe Chinese University of Hong Kong
The Chemistry of Some Common Soft DrugsThe Chemistry of Some Common Soft Drugs
10th April, 2006C hem
DrugsDrugs
Physiologicalchanges
Emotionalchanges
Behaviouralchanges
Medicines — Chemicals Against Diseases?
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"Good" Drugs"Good" Drugs
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"Bad" Drugs"Bad" Drugsvsvs
Penicillin
Morphine
Aspirin
Heroin
Cocaine
Amphetamines
Chemists always stride in modifying the chemical
structure of a compound in order to remove those
undesirable properties while retaining the
desirable ones.
Chemistry: The Central ScienceChemistry: The Central Science
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How do drugs work?How do drugs work?
1. Drug action at enzymes
2. Drug action at receptors
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Neurotransmitters and Receptor Molecules
Drug Action at ReceptorsDrug Action at Receptors
Cell
Receptor
Nucleus
Signal
Nerve
Response
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• Pain-killing drugs that also induce euphoria
NNARCOTIC ARCOTIC AANALGESICSNALGESICS
• Powerful central nervous system depressants that can induce sleep and reduce anxiety
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The Opium Alkaloids
A number of alkaloids can be isolated from the juice obtained from seed pods of the opium poppy.
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Three important opiates are:
They are the most effective pain-killers!
HO
HO
H
O
NMe
CH3COO
CH3COO
H
O
NMe
CH3O
HO
H
O
NMe
Morphine HeroinCodeine
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MMORPHINEORPHINE
• The most important narcotic analgesic in medicine — used for the relief of severe pain.
• When pure, it is an insoluble, odourless, white crystalline solid with a bitter taste.
• The principal alkaloid (~10% w/w) of raw opium.
• First isolated in 1805.
But it is an additive!But it is an additive!
HEROIN
• Also known as diacetyl morphine or diamorphine.
• Heroin is a semi-synthetic opiate drug which was
introduced commercially in 1898 after a pioneering
clinical research work by the German
pharmacologist Heinrich Dreser at Friedrich Bayer
and Co.
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O
CH3COO
CH3COO
H
NCH3
• It can be readily prepared by heating morphine with acetic acid:
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Acetylation
O
CH3COO
CH3COO
H
NCH3
O
HO
HO
H
NCH3
Morphine Heroin
+ (CH3CO)2O
Δ
• Heroin was found to be a highly
effective medication in the treatment of coughs, chest pains and the discomfort of tuberculosis.
• Dreser called it heroin, a name
derived from the German word for “heroic”.
• In terms of pain-killing activity, heroin is about 2–3
times stronger than morphine.
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• Abusers often feel a surge of pleasurable sensation, followed by drowsiness for several hours.
• Heroin crosses the blood–brain barrier soon after inhalation or injection. It is converted to morphine in the brain and binds rapidly to opiate receptors.
Effects of heroin
Treatment
The methadone treatment
• As a synthetic opiate,
methadone was developed by
the Nazis during World War II
when the supply of opium was
cut off.
• The most effective form of
treatment for addiction to
heroin and other narcotics.
Methadone
CCH
C
CH3
N CH3
CH3
CH2CH3
O
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SSTIMULANT TIMULANT DDRUGSRUGS
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N
NN
N
O
CH3
CH3
OH3C
Caffeine
A cup of tea or coffee?A cup of tea or coffee?
SSTIMULANT TIMULANT DDRUGSRUGS
CocaineCocaine
AmphetaminesAmphetamines
EcstasyEcstasy
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COCAINE — The most potent stimulant of natural origin
Cocaine is extracted from the leaves of coca plants, that grows almost exclusively on the South American Andes.
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N
Me
H
COOMe
H
O
C
O
It was first used as a local anesthetic in eye
surgery. It was also useful in surgery of the nose
and throat. However, it is seldom used nowadays
due to the development of safer anesthetic drugs.
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Coca-cola was introduced in 1886 as "a valuable brain-tonic and cure for all nervous afflictions".
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Four basic routes to coca intoxication:
(1) Chewing coca leaves (mixed with lime and ashes) or brewing a cup of coca-tea for refreshment by the South America Indians.
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(2) Cocaine sulfate — a low-grade stuff in the preparation of cocaine hydrochloride crystals from coca leaves.
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(3) Cocaine hydrochloride — an odourless, white crystalline solid with a bitter taste.
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(4) “Crack” — a street name given to cocaine free base.
HN
Me
H
COOMe
HO
CO
N
Me
H
COOMe
HO
CO
Cocaine hydrochloride Cocaine
OH-
H+
+
Cl-
AMPHETAMINES
Amphetamine is a powerful stimulant drug that increases the activity of the central nervous system.
Its effect is similar to that of adrenaline, but amphetamine acts for a much longer time in the body.
“Ice”
CH2CH NH2
CH3
CH2CH NH
CH3
Amphetamine Methamphetamine
CH3
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Amphetamines can be acquired legally by prescription. It has once been used extensively for weight reduction and treatment of mild depression.
Nowadays, it has been used to treat narcolepsy (a rare form of sleeping sickness) and childhood hyperactivity.
Amphetamine can induce an extremely high blood pressure that strokes or even heart failure may result.
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MDMA (3,4-Methylenedioxymethamphetamine)
(ECSTASY)
• A synthetic, psychoactive drug possessing stimulant and hallucinogenic properties.
• A close structural analogue of amphetamine.
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CH2CH
CH3
NH CH3O
H2C O
CH2 CH
CH3
NH CH3
methamphetamine
MDMA was first synthesized and patented by E. Merck & Co., Germany in 1914 as an appetite suppressant. The compound was never marketed.
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HALLUCINOGENS
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Marijuana: Some Chemistry of Cannabis
• The plant Cannabis sativa, which grows wild throughout most of the tropic and temperate regions of the world, has long been useful.
e.g. Stem tough fibers for making rope.
• Marijuana refers to the leaves and flowering tops of the cannabis plant.
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• Cannabis contains a variety of chemical substances
known as cannabinoids. Among the cannabinoid compounds, tetrahydrocannabinol (THC) is believed to be the active ingredient responsible the psychoactive effects of cannabis.
OH
H11C5 O
CH3
CH3CH3
Tetrahydrocannabinol (THC)
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• Smoking Cannabis increases
the pulse rate, distorts the sense of time, impairs motor functions, and leads to hallucinations.
• There is evidence that marijuana causes brain
damage (brain lesions).
• Unlike alcohol, THC can persist in the bloodstream
for several days as it is soluble in fats.
Effect of cannabis
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• Chemists can monitor the levels of THC in the
bloodstream and can identify its degradation products.
• Marijuana has some medical uses.
e.g. For treatment of glaucoma (high eye pressure) and for the control of nausea that afflicts cancer patients undergoing radiation treatment and chemotherapy.
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Lysergic Acid Diethylamide (LSD)
• The most potent hallucinogen and mood-changing
chemical known to man.
• It was originally synthesized by Albert
Hoffman at the Sandoz Laboratories in
Switzerland in 1938, but its hallucinogenic
effects were known in 1943 when Hoffman
accidentally ingested some.
N
N
CH3
C
O
N
CH2CH3
H CH2CH3
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• Lysergic acid is isolated from ergot fungus and can
be easily converted to LSD by replacing the acid
with a —N(CH2CH3)2 group.
• LSD is produced in crystalline form, or diluted as a
solution for production in ingestible forms.
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• At the time when LSD was first reported, the new
chemical appeared not to have any particularly useful medical properties, although it has been noted that “the experimental animals became restless during the narcosis”.
• Self-experiments by Hoffman:
17:00: Beginning dizziness, feeling of anxiety, visual distortions, symptoms of paralysis, desire to laugh.
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• It is generally believed that as a part of the structure of LSD is similar to that of serotonin (a brain amine), this may account for its fantastic neurophysiological effects.
• Because of its similarity to serotonin, LSD has been used to study mental illness in the 1950’s and 1960’s.
How does LSD work?
• The mechanism by which LSD causes hallucination still has not been established.
N
N
CH3
C
O
N
CH2CH3
H CH2CH3
HN
CH2CH2NH2
HO
SerotoninLSD
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Ketamine
• A general anaesthetic for veterinary use.
• Its hallucinatory effects are short-acting, lasting for
an hour or less.
• However, it can affect the sense, judgement, and
coordination for 18 to 24 hours.
O NHCH3
Cl
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Ketamine
Synthesis of Ketamine
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Cl
CN
+
MgBr
3 days
Cl O
Br2
Cl OBr
CH3NH2
Cl NCH3
BrClNHCH3
OΔ
o- -chlorobenzonitrile
cyclopentylGrignardreagent
Right: Drug usersLeft: Normal people
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far less serotonin activity