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?

C hem

"Good" Drugs"Good" Drugs

C hem

"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

C hem

How do drugs work?How do drugs work?

1. Drug action at enzymes

2. Drug action at receptors

C hem

C hem

Neurotransmitters and Receptor Molecules

Drug Action at ReceptorsDrug Action at Receptors

Cell

Receptor

Nucleus

Signal

Nerve

Response

C hem

• Pain-killing drugs that also induce euphoria

NNARCOTIC ARCOTIC AANALGESICSNALGESICS

• Powerful central nervous system depressants that can induce sleep and reduce anxiety

C hem

The Opium Alkaloids

A number of alkaloids can be isolated from the juice obtained from seed pods of the opium poppy.

C hem

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

C hem

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.

C hem

O

CH3COO

CH3COO

H

NCH3

• It can be readily prepared by heating morphine with acetic acid:

C hem

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.

C hem

• 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

C hem

SSTIMULANT TIMULANT DDRUGSRUGS

C hem

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

C hem

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.

C hem

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.

C hem

Coca-cola was introduced in 1886 as "a valuable brain-tonic and cure for all nervous afflictions".

C hem

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.

C hem

(2) Cocaine sulfate — a low-grade stuff in the preparation of cocaine hydrochloride crystals from coca leaves.

C hem

(3) Cocaine hydrochloride — an odourless, white crystalline solid with a bitter taste.

C hem

(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

C hem

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.

C hem

MDMA (3,4-Methylenedioxymethamphetamine)

(ECSTASY)

• A synthetic, psychoactive drug possessing stimulant and hallucinogenic properties.

• A close structural analogue of amphetamine.

C hem

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.

C hem

HALLUCINOGENS

C hem

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.

C hem

• 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)

C hem

• 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

C hem

• 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.

C hem

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

C hem

• 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.

C hem

• 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.

C hem

• 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

C hem

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

C hem

Ketamine

Synthesis of Ketamine

C hem

Cl

CN

+

MgBr

3 days

Cl O

Br2

Cl OBr

CH3NH2

Cl NCH3

BrClNHCH3

OΔ

o- -chlorobenzonitrile

cyclopentylGrignardreagent

Right: Drug usersLeft: Normal people

C hem

far less serotonin activity