Chapter 14 The Chemistry of Drugs
? The medicinal use of plants has been discovered
more than 2000 years ago,Greek physician
Dioscorides described the use of opium,in which
morphine is the main component.
? In 1806,morphine was isolated from opium.
? In 1820,quinine was isolated from the bark of the
cinchona tree.
? In 1860s,Pasteur discovered bacteria and phenol
and related compounds started to be used to
prevent bacteria infection.
? In 1930s,sulfur-containing compounds known as
surfa drugs were developed.
? In 1939,penicillin (antibiotic) was found.
? Today,there are more than 25,000 prescription
drugs (处方药 ) and 300,000 nonprescription drugs
(非处方药 ),
14.1 Drugs are classified by safety,social
acceptability,origin,and biological activity
? Classified according to safety and social
acceptability
Most drugs exhibit a broad spectrum of activity,Aspirin
relieves pain,reduces fever and inflammation,thins the
blood,causes ringing in the ears.
U.S,Drug Enforcement Agency Classification of Drugs
Classification Description Examples
Over-the-counter (OTC)
drugs
Available to anyone Aspirin,cough medicines
Permitted nonmedical drugs Available in food beverage and tobacco products Alcohol,caffeine,nicotine
Prescribe drugs Requires physician authorization Antibiotics,birth control pills
Control substance
Schedule 1 No medical use,high abuse potential Heroine,LSD,mescaline,marijuana
Schedule 2 Some medical use,high abuse potential Amphetamine,cocaine,morphine,codeine
Schedule 3 Prescription drugs,abuse potential Barbiturates,valium
Classified according to origin
Table 14.2
The Origin of Some Common Drug
Origin Drug Biological Effect
Natural product Caffeine
Reserpine
Vincristine
Penicilline
Morphine
Nerve stimulant
Hypertension reducer
Anticancer agent
Antibiotic
analgesic
Chemical derivative of natural
product
Prednisone
Ampicillin
LSD
Chloroquinine
Ethynodiol
diacetate
Antirheumatic
Antibiotic
Hallucinogenic
Antimalarial
Contraceptive
Synthetic Valium
Benadryl
Allobarbital
Phencyclidine
methadone
Antidepressant
Antihistamine
Sedative-hypnotic
Veterinary anesthetic
analgesic
14.2 The Lock-and-Key Model guides
chemists in synthesizing new drugs
all drugs that act like morphine have the same
basic three-dimensional shape as morphine
T-shaped three dimensional
structure found in all opioids
morphine
codeine heroine
Fig 14.2 many
drugs act by fitting
into receptor sites
on molecules
found in the body,
much as a key fits
in a lock
Drug molecule
(morphine)
Receptor site
Lock
Key
Most new medicinal drugs are still
discovered instead of designed.
Fig 14.3 ethnobotanists directed
natural-products chemists to the
yellow coating on the root of the
African Bobgunnua tree,
Indigenous people have known for
many generations that this
coating has medicinal properties,
From extracts of the coating,the
chemists isolated a compound
that is highly effective in treating
fungal infections,This compound,
produced by the tree to protect
itself from root tot,shows much
promise in the treatment of the
opportunistic fungal infections
that plague those suffering from
AIDS
Another important method of drug discovery is the
random screening of vast numbers of compounds.
N
O H
H
O
O
O
O
O
O
O
O
O H
O
O H
O
Taxol
Fig 14.4 originally isolated from the bark of the pacific yew tree,
Taxol is a complex natural product useful in the treatment of
various forms of cancer
Combinational Chemistry (组合化学 )
Tiny well or test tube
in which reagents B
and 4 are mixed.
Fig 14.5 (a) eight hypothetical starting materials A through D and 1 through 4 can be
combined in various ways to yield 16 products,each of which may have some biological
activity not found in any of the starting materials,(b) A multitude of products are thus
immediately available to be screened for medicinal activity.
14.3 Chemotherapy cures the host by killing the
disease
? The use of drugs that destroy disease-causing agents without
destroying the animal host is known as chemotherapy,It works by
taking advantage of the ways a disease-causing agent,also known as
a pathogen (病原体 ),is different from a host.
? Sulfa drugs （磺胺类药物） and antibiotics （抗生素） treat bacteria
infections
? Humans can use folic acid (叶酸 ) from outside sources,but bacteria
have to synthesize from PABA,
PABA
Folic acid
Several steps
Bacterial enzyme
Fig 14.6 bacterial enzymes use para-aminobenzoic acid (PABA) to synthesize folic acid.
C
O
O HN
H
H
S
O
N H 2
O
N
H
H
No folic acid
bacterial diePABA
sulfanilamide
Bacterial enzyme
Fig 14.7 sulfa drugs are metabolized to sulfanilamide,which binds to
the bacterial enzymes and keeps them from doing their job.
? Antibiotics
? Penicillin and related compounds (cephalosporins,头孢
霉素 ) kill bacteria by inactivating an enzyme responsible
for strengthening the bacteria cell wall,N H 2
O
N
H
N
S
C H 3
H O O
OO
N
H
O
N
S
C H 3
C H 3
O O H
Fig 14.8 Penicillins,such as penicillin G,and cephalosporin,such as cephalexin,as well as
most other antibiotics,are produced by microorganisms that can be mass-produced in
large vats,The antibiotics are then harvested and purified
penicillin G cephalexin
Chemotherapy can inhibit the ability of viruses to
replicate
Fig 14.9 viruses are much smaller than bacteria and many times
smaller than animal cells,(Notice the small dot representing the virus.)
the smallest of all pathogens,viruses consist mostly of nucleic acids
enclosed in a protein coat.
Figure 14.10 before a nucleoside,such as guanosine,Can be incorporated into RNA
or DNA,it must be activated by having three phosphate groups attached to it
Figure 14.11 Acyclovir
(zovirax) is a derivative of
the nucleoside
deoxyguanosine,And
zidovudine (AZT) is a
derivative of the
nucleoside
deoxythymidine
3 phosphate
group
enzyme
Acquired immune deficiency syndrome (AIDS)
Protease inhibitors (蛋白酶抑制剂 ) together with
nucleoside antiviral agents (核苷抗病毒剂 ) have
been used.
(a) the small green bodies cover
this white blood cell are human
immunodeficiency viruses
(b) the anatomy of HIV
the protease inhibitor nelfinavir
Cancer chemotherapy attacks rapidly growing cells
At present mortality rate,one in six of us will die of cancer.
Chemotherapy is most effective at the early stage of cancer because
drugs work best on cells when they are in the process of dividing,A
variety of chemicals may be used to selectively kill cells that are in the
process of dividing by attacking DNA.
N H
P
O
N
C l
C l
O
P t
C lC l
H 3 N N H 3
S-fluorouracil cycphosphamide cis-platin
Figure 14.15 These anticancer agents all kill dividing cells by targeting the cell’s DNA
Uracil
14.5
The nervous
system
is a network of
neurons
central nervous
system( brain and
spinal cord)
peripheral
nervous system
sensory
neurons
motor
neurons
Involuntary (conduct
signals from CNS to
cardiac nuscles,
smooth muscles,
glands)
Voluntary
(conduct signals
from CNS to
skeletal muscles)
Stress
(promote
emergency
functions)
Maintenance
(promote
nonemergency
functions)
fig 14.20 the two major divisions of the human
nervous system are the central nervous
system and the peripheral nervous system
Neurotransmitters (神经传递
介质 ) include
norepinephrine （去甲肾上
腺素）,acetylcholine （乙酰
胆碱）,dopamine （多巴
胺）,serotonin （血清素）,
and GABA （ γ-氨基丁酸）
The primary
neurotransmitter for stress
neurons is norepinephrine.
The primary
neurotransmitter for
maintenance neurons is
acetylcholine.
H O
H O
O H
N H 2
H 3 C
C N
C H 3
O C H 3
C H 3
Figure14.21 The chemical structures
of the stress neurotransmitter
norepinephrine and the maintenance
neurotransmitter acetylcholine
norepinephrine
acetylcholine
Dopamine plays a significant role in activating the
brain’s reward center,located in the hypothalamus
(下丘脑 ),giving a pleasurable sense.
Serotonin
C
O
H O
N H 2
Gamma aminobutytic acid
(GABA)
Figure 14.22 the chemical structures of three neurotransmitters
important to the central nervous system
H 2
C
C
H 2
N H 2H O
H O
Dopamine
Frontal lobe
Spinal cord
hypothalamuscerebellum
Figure 14.23 The human brain
14.6 Psychoactive drugs alter the mind or
behavior
? Stimulants (兴奋剂 ),Hallucinogens (致幻觉剂 ),depressants (抑制剂 ),
antipsychotics (安定药 ),antidepressants (抗抑郁剂 )
? Stimulants activate the stress neurons
? Stimulants mimic many of effects of neurotransmitter.
? They also boost the levels of these neurotransmitters in a synaptic
cleft by blocking their removal.
N H 2
C H 3
N
C H 3
C H 3C H 3
H
N
C H 3
C H 3
H
Figure 14.24 Amphetamines are a family of compounds structurally related to the
neurotransmitters morepinephrine and dopamine.
Amphetamines morepinephrine
dopamine
Fig 14.25 1)
neurotransmitters bind to
their postsynaptic
receptors,
2)neurotransmitters are
reabsorbed by the
presynaptic neuron that
released them through
proteins embedded in the
presynaptic membrane,3)
A drug that interferes with
re-uptake causes a buildup
of neurotransmitters in the
synaptic cleft
Cocaine
N
O
O C H
3
O
O
C H
3
Figure 14.26 The south
American coca plant has been
used by indigenous cultures
for many years in religious
ceremonies and as an aid to
staying awake on long
hunting trips,Leaves are
either chewed or ground to a
powder that is inhaled nasally
Fig 14.27 cocaine affects dopamine levels in the synaptic clefts of the brain’s reward center
1) High levels of dopamine
remain active in the synaptic
cleft as cocaine blocks
dopamine re-uptake sites,
This causes cocaine’s
euphoric effect.
2) Dopamine is metabolized
and deactivated as it loiters in
the synaptic cleft awaiting re-
uptake
3)After cocaine is metabolized
and deactivated,dopamine re-
uptake is no longer blocked,but
there is very little dopamine in
the synaptic cleft or in the
neurons and the cocaine user
experiences extreme depression
? Caffeine
? Caffeine can be found in coffee beans,teas,
kolanuts,and cocoa beans.
? Caffeine facilitates the release of
norepinephrine into synaptic clefts.
? Caffeine can be well dissolved in carbon
dioxide,N
N
N
N
O
O
C H 3
H 3 C
C H 3
caffeine
Fig14.28 a coffee with its ripening caffeine-containing beans
? Nicotine
? Nicotine has a similar chemical structure to acetylcholine,
and can depress the maintenance neurons,leading to
relaxation and increased digestion,But depressed
maintenance neuron favors the stress neurons,leading to
increased blood pressure.
? The lethal dose of nicotine in humans is about 60 mg.
N
N +
C H 3
H
C
O
H 3 C O
N +
C H 3
C H 3
C H 3
acetylcholinenicotine
Fig14.29 nicotine is able to bind to receptor sites for acetylcholine because of
structural similarities
? Hallucinogens and cannabinoids alter perceptions
? LSD is the most famous hallucinogen and was
synthesized in 1938 by Albert Hoffmann.
N
N H 2
R o t a t i o n
N
H
N H 2
H
R o t a t i o n
N
H
N H 2
Serotonin
Figure 14.31 The side chain of serotonin can rotate into a number of conformations,
Upon binding to a receptor site,However,the side chain is likely to be a held in
conformation 3,Note how the LSD molecule can be superimposed on structure 3,LSD
may therefore be thought of as a modified serotonin molecule in which the side chain
is held in the ideal conformation for receptor binding
Lysergic acid diethylamide
? Cannabinoids are the psychoactive
components of marijuana (大麻 ).
O
C H 3
O H
H 3 C
H 3 C
Figure 14.34 The major psychoactive component marijuana is
Δ9-tetrahydrocannabinol.
Δ9-tetrahydrocannabinol.
? Depressants inhibit the ability of neurons to conduct
impulses
? Alcohol,barbiturates (巴比妥酸盐 ),benzodiazepines
? Alcohol mimics the effect of GABA by binding to GABA
receptor sites,allowing chlorine ions to enter the neuron.
Cl-
Cl-
Ethyl
alcohol
Channel
open
Cl- Cl
-
Cl-
Cl- Channel open
Chloride ion
channel protein
GABA
GABA
receptor site
Outside neuron
inside neuronChannel closed
Fig 14.38 (a) when GABA binds to its receptor site,a channel opens to allow
negatively charged chloride ions into the neurons,The high concentration of
negative ions inside the neuron prevents the electric potential from reversing
from negative to positive,Because that reversal is necessary if an impulse is to
travel through a neuron,no impulse can move through the neuron,(b) ethyl
alcohol mimics GABA receptor sites
Neuron cell
membrane
Antipsychotics and antidepressants boost synaptic-cleft
concentrations of neurotransmitters
Fig 14.39 the receptor sites
for barbiturates and
benzodiazepines are
adjacent to GABA receptor
sites,(a ) Barbiturates open
up chloride-ion channels
on their own,(b)
benzodiazepines can not,
(c) rather,benzodiazepines
help GABA in its channel-
opening task
Cl-
Cl-Cl-
Cl-
Benzodiazepine
receptor site
Barbiturate
receptor siteGABA
14.7 Pain relievers inhibit the transimission or
perception of pain
? Anesthetics (麻醉剂 ) prevent neurons from transmitting
sensations to the CNS.
? Local anesthetics
N H
2
C
O C H
3
O
N H
2
C
O
O
N
C H
2
C H
3
C H
2
C H
3
N C
O
N
C H
3
C H
3
O
H
C H
3
C H
3
C H
3
N
C
O
C H
2
N
C H
2
C H
3
C H
2
C H
3
C
O
N C H
3
CC H
3
O
O
O
Aromatic ring Intermediate
chain
Amine
group
Fig 14.43 local
anesthetics have
similar structural
features,including an
aromatic ring,an
intermediate chain,
and an amine group,
Ask your dentist
which ones he or she
uses for your
treatment
? General anesthetics
CF
H
H
O C C F 3
C F 3
H
Figure 14.44 The chemical structures of sevoflurane and nitrous oxide.
N N
O
sevoflurane nitrous oxide
? Analgesics (止痛药 )
C
O H
O
O H
O H
O H
O H
O
No prostaglandin
enzymeO H
O
Over- the- counter
analgesic bound
to enzyme
Arachidonic acid
prostaglandin
Fig 14.45 (a) prostaglandins,which cause pain
signals to be sent to the brain,are sunthesized by
the body in response to injury,The starting material
for all prostaglandin is arachidonic acid,which is
found in the plasma membrane of all cells,
Arachidonc acid is transformed to prostaglandin with
the help of an enzyme,There are a variety of
prostaglandins,each having its own effect,but all
have a chemical strucrure resembling the one
shown here,(b) analgesics inhibit the synthesis of
prostaglandin by binding to the arachidonic acid
receptor site on the enzyme,With no prostaglandins,
no pain signals are generated,
(a)
(b)
C
O H
O
C
O
O
C H 3
O H
H
3
C
O
C H
3
H
3
C
C
O H
H
3
C
O
C H
3
O
N
H
C H 3
O
O H
Figure 14.46 Aspirin,ibuprofen,and naproxen block the formation of prostaglandins
responsible for pain,fever,and inflammation,Acetaminophen blocks the formation only
of prostaglandins responsible for pain and fever.
Aspirin ibuprofen naproxen Acetaminophen
? Opioid analgesics
? Opioids mimic the
action of endorphin
(内啡肽 ).
Heroin
Fig 14.48 the structure of
methadone superimposed on
that of morphine
Methadone/morphine
14.8 Drugs for the heart open blood vessels or
alter heart rate
? arteriosclerosis (动脉硬化 ) leads to arrhythmia
(心律失常 ) and clogging of blood vessel.
? Vasodilators (血管扩张药 ) expand blood vessels
by releasing NO.
H 2 C CH C H 2
O OO
N O 2 N O 2 N O 2
C
HH 3 C
H 3 C C H 2 C H 2 O N O
Figure 14.49 The vasodilators nitroglycerin and amyl nitrite,
nitroglycerin amyl nitrite
? Beta blockers (干扰素 ) and calcium-channel
blockers lower the blood pressure,
O N C H 3
C H 3
H
N
H
H 3 C C H 3
C C
OO
O C H 3H 3 C O
Figure 14.50 Propranolol is a beta blocker,and nifedipine is a calcium-channel blocker
Propranolol(inderal) Nifedipine
? The medicinal use of plants has been discovered
more than 2000 years ago,Greek physician
Dioscorides described the use of opium,in which
morphine is the main component.
? In 1806,morphine was isolated from opium.
? In 1820,quinine was isolated from the bark of the
cinchona tree.
? In 1860s,Pasteur discovered bacteria and phenol
and related compounds started to be used to
prevent bacteria infection.
? In 1930s,sulfur-containing compounds known as
surfa drugs were developed.
? In 1939,penicillin (antibiotic) was found.
? Today,there are more than 25,000 prescription
drugs (处方药 ) and 300,000 nonprescription drugs
(非处方药 ),
14.1 Drugs are classified by safety,social
acceptability,origin,and biological activity
? Classified according to safety and social
acceptability
Most drugs exhibit a broad spectrum of activity,Aspirin
relieves pain,reduces fever and inflammation,thins the
blood,causes ringing in the ears.
U.S,Drug Enforcement Agency Classification of Drugs
Classification Description Examples
Over-the-counter (OTC)
drugs
Available to anyone Aspirin,cough medicines
Permitted nonmedical drugs Available in food beverage and tobacco products Alcohol,caffeine,nicotine
Prescribe drugs Requires physician authorization Antibiotics,birth control pills
Control substance
Schedule 1 No medical use,high abuse potential Heroine,LSD,mescaline,marijuana
Schedule 2 Some medical use,high abuse potential Amphetamine,cocaine,morphine,codeine
Schedule 3 Prescription drugs,abuse potential Barbiturates,valium
Classified according to origin
Table 14.2
The Origin of Some Common Drug
Origin Drug Biological Effect
Natural product Caffeine
Reserpine
Vincristine
Penicilline
Morphine
Nerve stimulant
Hypertension reducer
Anticancer agent
Antibiotic
analgesic
Chemical derivative of natural
product
Prednisone
Ampicillin
LSD
Chloroquinine
Ethynodiol
diacetate
Antirheumatic
Antibiotic
Hallucinogenic
Antimalarial
Contraceptive
Synthetic Valium
Benadryl
Allobarbital
Phencyclidine
methadone
Antidepressant
Antihistamine
Sedative-hypnotic
Veterinary anesthetic
analgesic
14.2 The Lock-and-Key Model guides
chemists in synthesizing new drugs
all drugs that act like morphine have the same
basic three-dimensional shape as morphine
T-shaped three dimensional
structure found in all opioids
morphine
codeine heroine
Fig 14.2 many
drugs act by fitting
into receptor sites
on molecules
found in the body,
much as a key fits
in a lock
Drug molecule
(morphine)
Receptor site
Lock
Key
Most new medicinal drugs are still
discovered instead of designed.
Fig 14.3 ethnobotanists directed
natural-products chemists to the
yellow coating on the root of the
African Bobgunnua tree,
Indigenous people have known for
many generations that this
coating has medicinal properties,
From extracts of the coating,the
chemists isolated a compound
that is highly effective in treating
fungal infections,This compound,
produced by the tree to protect
itself from root tot,shows much
promise in the treatment of the
opportunistic fungal infections
that plague those suffering from
AIDS
Another important method of drug discovery is the
random screening of vast numbers of compounds.
N
O H
H
O
O
O
O
O
O
O
O
O H
O
O H
O
Taxol
Fig 14.4 originally isolated from the bark of the pacific yew tree,
Taxol is a complex natural product useful in the treatment of
various forms of cancer
Combinational Chemistry (组合化学 )
Tiny well or test tube
in which reagents B
and 4 are mixed.
Fig 14.5 (a) eight hypothetical starting materials A through D and 1 through 4 can be
combined in various ways to yield 16 products,each of which may have some biological
activity not found in any of the starting materials,(b) A multitude of products are thus
immediately available to be screened for medicinal activity.
14.3 Chemotherapy cures the host by killing the
disease
? The use of drugs that destroy disease-causing agents without
destroying the animal host is known as chemotherapy,It works by
taking advantage of the ways a disease-causing agent,also known as
a pathogen (病原体 ),is different from a host.
? Sulfa drugs （磺胺类药物） and antibiotics （抗生素） treat bacteria
infections
? Humans can use folic acid (叶酸 ) from outside sources,but bacteria
have to synthesize from PABA,
PABA
Folic acid
Several steps
Bacterial enzyme
Fig 14.6 bacterial enzymes use para-aminobenzoic acid (PABA) to synthesize folic acid.
C
O
O HN
H
H
S
O
N H 2
O
N
H
H
No folic acid
bacterial diePABA
sulfanilamide
Bacterial enzyme
Fig 14.7 sulfa drugs are metabolized to sulfanilamide,which binds to
the bacterial enzymes and keeps them from doing their job.
? Antibiotics
? Penicillin and related compounds (cephalosporins,头孢
霉素 ) kill bacteria by inactivating an enzyme responsible
for strengthening the bacteria cell wall,N H 2
O
N
H
N
S
C H 3
H O O
OO
N
H
O
N
S
C H 3
C H 3
O O H
Fig 14.8 Penicillins,such as penicillin G,and cephalosporin,such as cephalexin,as well as
most other antibiotics,are produced by microorganisms that can be mass-produced in
large vats,The antibiotics are then harvested and purified
penicillin G cephalexin
Chemotherapy can inhibit the ability of viruses to
replicate
Fig 14.9 viruses are much smaller than bacteria and many times
smaller than animal cells,(Notice the small dot representing the virus.)
the smallest of all pathogens,viruses consist mostly of nucleic acids
enclosed in a protein coat.
Figure 14.10 before a nucleoside,such as guanosine,Can be incorporated into RNA
or DNA,it must be activated by having three phosphate groups attached to it
Figure 14.11 Acyclovir
(zovirax) is a derivative of
the nucleoside
deoxyguanosine,And
zidovudine (AZT) is a
derivative of the
nucleoside
deoxythymidine
3 phosphate
group
enzyme
Acquired immune deficiency syndrome (AIDS)
Protease inhibitors (蛋白酶抑制剂 ) together with
nucleoside antiviral agents (核苷抗病毒剂 ) have
been used.
(a) the small green bodies cover
this white blood cell are human
immunodeficiency viruses
(b) the anatomy of HIV
the protease inhibitor nelfinavir
Cancer chemotherapy attacks rapidly growing cells
At present mortality rate,one in six of us will die of cancer.
Chemotherapy is most effective at the early stage of cancer because
drugs work best on cells when they are in the process of dividing,A
variety of chemicals may be used to selectively kill cells that are in the
process of dividing by attacking DNA.
N H
P
O
N
C l
C l
O
P t
C lC l
H 3 N N H 3
S-fluorouracil cycphosphamide cis-platin
Figure 14.15 These anticancer agents all kill dividing cells by targeting the cell’s DNA
Uracil
14.5
The nervous
system
is a network of
neurons
central nervous
system( brain and
spinal cord)
peripheral
nervous system
sensory
neurons
motor
neurons
Involuntary (conduct
signals from CNS to
cardiac nuscles,
smooth muscles,
glands)
Voluntary
(conduct signals
from CNS to
skeletal muscles)
Stress
(promote
emergency
functions)
Maintenance
(promote
nonemergency
functions)
fig 14.20 the two major divisions of the human
nervous system are the central nervous
system and the peripheral nervous system
Neurotransmitters (神经传递
介质 ) include
norepinephrine （去甲肾上
腺素）,acetylcholine （乙酰
胆碱）,dopamine （多巴
胺）,serotonin （血清素）,
and GABA （ γ-氨基丁酸）
The primary
neurotransmitter for stress
neurons is norepinephrine.
The primary
neurotransmitter for
maintenance neurons is
acetylcholine.
H O
H O
O H
N H 2
H 3 C
C N
C H 3
O C H 3
C H 3
Figure14.21 The chemical structures
of the stress neurotransmitter
norepinephrine and the maintenance
neurotransmitter acetylcholine
norepinephrine
acetylcholine
Dopamine plays a significant role in activating the
brain’s reward center,located in the hypothalamus
(下丘脑 ),giving a pleasurable sense.
Serotonin
C
O
H O
N H 2
Gamma aminobutytic acid
(GABA)
Figure 14.22 the chemical structures of three neurotransmitters
important to the central nervous system
H 2
C
C
H 2
N H 2H O
H O
Dopamine
Frontal lobe
Spinal cord
hypothalamuscerebellum
Figure 14.23 The human brain
14.6 Psychoactive drugs alter the mind or
behavior
? Stimulants (兴奋剂 ),Hallucinogens (致幻觉剂 ),depressants (抑制剂 ),
antipsychotics (安定药 ),antidepressants (抗抑郁剂 )
? Stimulants activate the stress neurons
? Stimulants mimic many of effects of neurotransmitter.
? They also boost the levels of these neurotransmitters in a synaptic
cleft by blocking their removal.
N H 2
C H 3
N
C H 3
C H 3C H 3
H
N
C H 3
C H 3
H
Figure 14.24 Amphetamines are a family of compounds structurally related to the
neurotransmitters morepinephrine and dopamine.
Amphetamines morepinephrine
dopamine
Fig 14.25 1)
neurotransmitters bind to
their postsynaptic
receptors,
2)neurotransmitters are
reabsorbed by the
presynaptic neuron that
released them through
proteins embedded in the
presynaptic membrane,3)
A drug that interferes with
re-uptake causes a buildup
of neurotransmitters in the
synaptic cleft
Cocaine
N
O
O C H
3
O
O
C H
3
Figure 14.26 The south
American coca plant has been
used by indigenous cultures
for many years in religious
ceremonies and as an aid to
staying awake on long
hunting trips,Leaves are
either chewed or ground to a
powder that is inhaled nasally
Fig 14.27 cocaine affects dopamine levels in the synaptic clefts of the brain’s reward center
1) High levels of dopamine
remain active in the synaptic
cleft as cocaine blocks
dopamine re-uptake sites,
This causes cocaine’s
euphoric effect.
2) Dopamine is metabolized
and deactivated as it loiters in
the synaptic cleft awaiting re-
uptake
3)After cocaine is metabolized
and deactivated,dopamine re-
uptake is no longer blocked,but
there is very little dopamine in
the synaptic cleft or in the
neurons and the cocaine user
experiences extreme depression
? Caffeine
? Caffeine can be found in coffee beans,teas,
kolanuts,and cocoa beans.
? Caffeine facilitates the release of
norepinephrine into synaptic clefts.
? Caffeine can be well dissolved in carbon
dioxide,N
N
N
N
O
O
C H 3
H 3 C
C H 3
caffeine
Fig14.28 a coffee with its ripening caffeine-containing beans
? Nicotine
? Nicotine has a similar chemical structure to acetylcholine,
and can depress the maintenance neurons,leading to
relaxation and increased digestion,But depressed
maintenance neuron favors the stress neurons,leading to
increased blood pressure.
? The lethal dose of nicotine in humans is about 60 mg.
N
N +
C H 3
H
C
O
H 3 C O
N +
C H 3
C H 3
C H 3
acetylcholinenicotine
Fig14.29 nicotine is able to bind to receptor sites for acetylcholine because of
structural similarities
? Hallucinogens and cannabinoids alter perceptions
? LSD is the most famous hallucinogen and was
synthesized in 1938 by Albert Hoffmann.
N
N H 2
R o t a t i o n
N
H
N H 2
H
R o t a t i o n
N
H
N H 2
Serotonin
Figure 14.31 The side chain of serotonin can rotate into a number of conformations,
Upon binding to a receptor site,However,the side chain is likely to be a held in
conformation 3,Note how the LSD molecule can be superimposed on structure 3,LSD
may therefore be thought of as a modified serotonin molecule in which the side chain
is held in the ideal conformation for receptor binding
Lysergic acid diethylamide
? Cannabinoids are the psychoactive
components of marijuana (大麻 ).
O
C H 3
O H
H 3 C
H 3 C
Figure 14.34 The major psychoactive component marijuana is
Δ9-tetrahydrocannabinol.
Δ9-tetrahydrocannabinol.
? Depressants inhibit the ability of neurons to conduct
impulses
? Alcohol,barbiturates (巴比妥酸盐 ),benzodiazepines
? Alcohol mimics the effect of GABA by binding to GABA
receptor sites,allowing chlorine ions to enter the neuron.
Cl-
Cl-
Ethyl
alcohol
Channel
open
Cl- Cl
-
Cl-
Cl- Channel open
Chloride ion
channel protein
GABA
GABA
receptor site
Outside neuron
inside neuronChannel closed
Fig 14.38 (a) when GABA binds to its receptor site,a channel opens to allow
negatively charged chloride ions into the neurons,The high concentration of
negative ions inside the neuron prevents the electric potential from reversing
from negative to positive,Because that reversal is necessary if an impulse is to
travel through a neuron,no impulse can move through the neuron,(b) ethyl
alcohol mimics GABA receptor sites
Neuron cell
membrane
Antipsychotics and antidepressants boost synaptic-cleft
concentrations of neurotransmitters
Fig 14.39 the receptor sites
for barbiturates and
benzodiazepines are
adjacent to GABA receptor
sites,(a ) Barbiturates open
up chloride-ion channels
on their own,(b)
benzodiazepines can not,
(c) rather,benzodiazepines
help GABA in its channel-
opening task
Cl-
Cl-Cl-
Cl-
Benzodiazepine
receptor site
Barbiturate
receptor siteGABA
14.7 Pain relievers inhibit the transimission or
perception of pain
? Anesthetics (麻醉剂 ) prevent neurons from transmitting
sensations to the CNS.
? Local anesthetics
N H
2
C
O C H
3
O
N H
2
C
O
O
N
C H
2
C H
3
C H
2
C H
3
N C
O
N
C H
3
C H
3
O
H
C H
3
C H
3
C H
3
N
C
O
C H
2
N
C H
2
C H
3
C H
2
C H
3
C
O
N C H
3
CC H
3
O
O
O
Aromatic ring Intermediate
chain
Amine
group
Fig 14.43 local
anesthetics have
similar structural
features,including an
aromatic ring,an
intermediate chain,
and an amine group,
Ask your dentist
which ones he or she
uses for your
treatment
? General anesthetics
CF
H
H
O C C F 3
C F 3
H
Figure 14.44 The chemical structures of sevoflurane and nitrous oxide.
N N
O
sevoflurane nitrous oxide
? Analgesics (止痛药 )
C
O H
O
O H
O H
O H
O H
O
No prostaglandin
enzymeO H
O
Over- the- counter
analgesic bound
to enzyme
Arachidonic acid
prostaglandin
Fig 14.45 (a) prostaglandins,which cause pain
signals to be sent to the brain,are sunthesized by
the body in response to injury,The starting material
for all prostaglandin is arachidonic acid,which is
found in the plasma membrane of all cells,
Arachidonc acid is transformed to prostaglandin with
the help of an enzyme,There are a variety of
prostaglandins,each having its own effect,but all
have a chemical strucrure resembling the one
shown here,(b) analgesics inhibit the synthesis of
prostaglandin by binding to the arachidonic acid
receptor site on the enzyme,With no prostaglandins,
no pain signals are generated,
(a)
(b)
C
O H
O
C
O
O
C H 3
O H
H
3
C
O
C H
3
H
3
C
C
O H
H
3
C
O
C H
3
O
N
H
C H 3
O
O H
Figure 14.46 Aspirin,ibuprofen,and naproxen block the formation of prostaglandins
responsible for pain,fever,and inflammation,Acetaminophen blocks the formation only
of prostaglandins responsible for pain and fever.
Aspirin ibuprofen naproxen Acetaminophen
? Opioid analgesics
? Opioids mimic the
action of endorphin
(内啡肽 ).
Heroin
Fig 14.48 the structure of
methadone superimposed on
that of morphine
Methadone/morphine
14.8 Drugs for the heart open blood vessels or
alter heart rate
? arteriosclerosis (动脉硬化 ) leads to arrhythmia
(心律失常 ) and clogging of blood vessel.
? Vasodilators (血管扩张药 ) expand blood vessels
by releasing NO.
H 2 C CH C H 2
O OO
N O 2 N O 2 N O 2
C
HH 3 C
H 3 C C H 2 C H 2 O N O
Figure 14.49 The vasodilators nitroglycerin and amyl nitrite,
nitroglycerin amyl nitrite
? Beta blockers (干扰素 ) and calcium-channel
blockers lower the blood pressure,
O N C H 3
C H 3
H
N
H
H 3 C C H 3
C C
OO
O C H 3H 3 C O
Figure 14.50 Propranolol is a beta blocker,and nifedipine is a calcium-channel blocker
Propranolol(inderal) Nifedipine
