PART Ⅳ

AGENTS ACTING ON THE

CENTRAL NERVOUS SYSTEM

Liu Juntian
 CHAPTER 13 General Consideration
1.composition of nervous system:
(1)central and peripheral nervous systems.
(2)neuron and synapse.*
2.function of CNS: regulation of body function.
3.activity of neuron(conduction of impulse)
(1) AP:
(2) neurotransmitter:
①NA,Ach,DA,GABA,glutamate,glycine,5HT,
histamine, opioid peptides and tachykinins.
②biosynthesis,storage,release,degradation,
reuptake.
 CHAPTER 13 General Consideration
1.composition of nervous system:
(1)central and peripheral nervous systems.
(2)neuron and synapse.
2.function of CNS: regulation of body function.
3.activity of neuron(conduction of impulse)
(1) AP:
(2) neurotransmitter:
①NA,Ach,DA,GABA,glutamate,glycine,5HT,
histamine, opioid peptides and tachykinins.
②biosynthesis,storage,release,degradation,
reuptake.*
 (3)receptor *
(4)conduction of impulse cross synapse:
presynaptic neuron release neurotransmitter
synaptic cleft neurotransmitter interacts with r
eceptor neurotransmitter-receptor complex initiat
es a sequence of events modulate the electrical a
ctivity of the postsynaptic neuron.
4.mechanism of drug on CNS
(1)  axon: slow or block the axonal electrical
conduction.
(2)  synapse:
①affect transmitrer.
②affect receptor.
③directly act on ion channel.
 (3)receptor
(4)conduction of impulse cross synapse:
presynaptic neuron release neurotransmitter
synaptic cleft neurotransmitter interacts wit
h receptor neurotransmitter-receptor complex i
nitiates a sequence of events modulate the ele
ctrical activity of the postsynaptic neuron. *
4.mechanism of drug on CNS
(1)  axon: slow or block the axonal electrical
conduction.
(2)  synapse:
①affect transmitrer.
②affect receptor.
③directly act on ion channel.
 (3)receptor
(4)conduction of impulse cross synapse:
presynaptic neuron release neurotransmitter
synaptic cleft neurotransmitter interacts with r
eceptor neurotransmitter-receptor complex initiat
es a sequence of events modulate the electrical
activity of the postsynaptic neuron.
4.mechanism of drug on CNS
(1)  axon: slow or block the axonal electrical
conduction.
(2)  synapse:
①affect transmitrer.
②affect receptor.
③directly act on ion channel.
5.BBB
(1)  structure
barrier between blood and brain cell;
3 parts barrier between blood and cerebrospinal fluid
barrier between brain cell and cerebrospinal
fluid.
endothelial cell lining capillaries.
(2)function: restrict the passage of polar compounds a
nd macro- molecules from blood into the brain.
(3)Pharmacological significance
 CHAPTER 14 Sedative-Hypnotics

【 classification 】
1. benzodiazepines.
2. barbiturates.
3.other agents: e.g.chloral hydrate.
【 general use 】
anxiety, insomnia, convulsion, epilepsy etc.
 Benzodiazepines
【 classification 】
1.short-acting
triazolam(T1/2 2~4h)
2.intermediate-acting
chlordiazepoxide (T1/2 5~10h)
oxazepam (T1/2 5~10h)
3.long-acting
diazepam (T1/2 30~60h)
flurazepam (T1/2 50~100h)
【 pharmacokinetics 】
The benzodiazepines are lipophilic and
are rapidly and completely absorbed after o
ral administration and are distributed throug
hout the body.Most benzodiazepines are m
etabolized by the hepatic microsomal meta
bolizing system to compounds that are also
active.The benzodiazepines are excreted in
urine as glucuronides or oxidized metabolit
es.
【 mechanism of action 】
There are benzodiazepine receptors (BZ
R) in CNS,which are separate from but adjac
ent to receptor for GABA. Benzodiazepines a
ctivate the receptors, which promotes GABA
binding to GABA receptors. Binding of GABA
to its receptors may open Cl— channel and fa
cilitate Cl— entry into neurons. The influx of c
hloride ions cause a small hyperpolarization
that moves the postsynaptic potential away fr
om its firing threshold and inihibits the formati
on of action potentials,which produces an inh
ibitory effect on neuronal conduction.*
【 pharmacologic effects and therapeutic uses 】
Benzodiazepines may produce antianxiety, sedation,
hypnosis, anticonvulsion and respiratory depression wi
th the increase of doses.
DOSE,ADMINISTRATION
1.antianxiety
(1)effect
All sedative-hypnotic drugs are capable of relieving
anxiety at sedative doses, but benzodiazepines exert a
ntianxiety action at the lowest effective doses that do n
ot cause sedation.
(2)use
to relieve anxiety states, including restlessness, wor
ry, stress and phobia states.
common drug: chlordiazepoxide,diazepam.
2. sedation
 use: general anesthesis; tracheoscopy examination
and electric defibrillation (temporary loss of
memory,i.v.).
common drug: diazepam.
3. hypnosis
(1)effect
to reduce awaking times, prolong sleep time an
d shorten sleep latency.
(2)use
insomnia, especially insomnia with anxiety.
common drug:flurazepam, temazepam,triazolam
4. anticonvulsant effects
(1)effect
to inhibit the development and spread of epilep
tiform activity in the CNS.
(2) use: convulsion and status epilepticus.
(3)common drug:
①clonazepam for chronic treatment of epilepsy;
②diazepam for terminating grand mal epileptic
seizures and status epilepticus;
③chlordiazepoxide,clorazepate,diazepam and
oxazepam for alcohol withdrawal.
5.relaxation of muscle
(1)effect
inhibitory effects on polysynaptic reflexes and int
ernuncial transmission in CNS, leading to muscle rel
axation.
(2)use: relaxing muscle spasm induced by cerebral
palsy.
common drug: diazepam.
【 adverse effects 】
Benzodiazepines have a low toxicity a
nd wide margin of safety.
1.central inhibitory effect
dizziness, asthenia, drowsiness.
2. tolerance, dependence and addiction.
3.acute toxication:
flumazenil--competitively NZR blocker.
 Barbiturates
【 classification 】
1. ultra-short-acting
thiopental(action of duration--0.25h).
2. short-acting
secobarbital (action of duration—2~3h).
3.intermediate-acting
pentobarbital and amobarbital (action of d
uration—3~6h).
4. long-acting:
phenobarbital (action of duration—6~8h).
【 pharmacokinetics 】
1.Duration of action depends on rate of meta
bolic degradation, degree of lipid solubility,
extent of binding to serum proteins. Ultra-s
hort-acting barbiturates are highly lipid-sol
uble, whereas long- acting barbiturates are
lowly lipid-soluble.
2.redistribution.
3.excretion via kidney. Alkalinization of urine
profoundly promotes excretion of barbitura
tes.
【 mechanism of action 】
①enhance effects of GABA.
②interfere with sodium and potassium transp
ort across cell membrane that leads to inhi
bition of the mesencephalic reticular activa
ting system.
③directly activate chloride channel,prolong t
he opening time of chloride channel to incr
ease influx of Cl- to decrease membrane p
otential in the large dose.
【 pharmacologic effects 】
1.to depress CNS at all levels in a dose-dependent
fasion. As dose of barbiturates increases, they p
roduce sedative, hypnosis, anticonvulsion, anest
hesia, central respiratory depression and depres
sion of vasomotor center respectively.
2.augment action of other CNS depressants.
3.shorten amount of time spent in REMS.
4.induce hepatic microsomal drug-metabolizing en
zymes.
clinical significance:
(1)to increase degradation of the barbiturates, ulti
mately leading to barbiturate tolerance.
(2)to increase inactivation and decreased action o
f other compounds in drug interaction.
【 therapeutic uses 】
DOSE,ADMINISTRATION
1.sedation and hypnosis: Intermediate and long-acting b
arbiturates, P.O.
disadvantages:
①narrow therapeutic-to-toxic dosage range;
②supressing REMS;
③tolerance ;
④high potential for physical dependence and abuse
⑤drug interaction secondary to microsomal enzyme in
duction.
2.anticonvulsion: phenobarbital, pentobarbital or amobar
bital,in injection.
3.antiepileptism: phenobarbital for epileptism in infant an
d children, in injection.
4.intravenous anesthetics or intravenous adjunct to
 surgical anesthetics, e.g. thiopental.
5.Barbiturates, especially in anesthetic doses, signifi
cantly decrease oxygen utilization by brain, which
may be of value in lessening cerebral edema caus
ed by surgery or trauma and in protecting against
cerebral infarction duration cerebral ischemia.
6.hyperbilirubinemia and kernicterus in the neonate.
【 adverse effects 】
1.CNS depressant effects: oversedation,nightmare.
2.dependence: physiologic and psychological depen
dence. Withdrawal of barbiturates may result in gr
and mal seizures, severe tremors, vivid hallucinati
ons, and psychoses. Abrupt withdrawal should be
avoided.
3.acute barbiturate overdosage
(1)clinical menifestation
coma, diminished reflexes, severe respirator
y depression, cardiovascular collapse, and r
enal failure.
(2)Treatment
①supporting respiration and circulation;
②alkalizing the gastric juice, the body fluids
and the urine(sodium bicarbonate),
③diuresis.
 Differentiation of barbiturates with benzodiazepines
benzodiazepines barbiturates
1.antianxiety:
dose lower than same dose as
one for sedation. for sedation.
2.hypnosis:no shorteningREMS shortening REMS
3.central muscular have no
relaxation:
4.anaesthesis: no have
5.hepatic micro- no have
some induction:
6.margin of safety: wide narrow
7.depression of weak strong
respiration:
 Chloral hydrate
1.a relatively safe hypnotic drug, inducing sle
ep in a half hour and lasting about 6 hours.
2.relatvely small reduction in REM sleep.
3.use:children and the elderly with
insomania, most effective for 1-3 nights.
4.bad-tasting and irritating to the gastro-
intestinal tract, administered by enema in
children.
5.addiction can occur.
 Paraldehyde
1.The CNS depressant activity of
paraldehyde resembles that of alcohol,
chloral hydrate and the barbiturates.
2.use: exclusively for patients undergoing
withdrawal from alcohol and for patients
with hepatic or renal failure.
CHAPTER 15 Agents Used in the Treatm
ent of Seizures
1.etiology
(1)primary epilepsy: inherited abnormality.
(2)secondary epilepsy:such as tumors, hea
d injury,hypoglycemia, meningeal infection,
or rapid withdrawal of alcohol from an alcoh
olic.
2.pathogenesis
sudden,excessive and abnormal discharg
e of cerebral neurons which diffuses to local
or whole brain.
3. clinic manifestation
regional or whole brain dysfunction: mot
or, vegetative and mental episodes, even l
oss of consciousness etc..
4.classification
(1)generalized
①grand mal epilepsy(tonic-clonic):
epilepticism(status epilepticus)
②absence epilepsy(petit mal):
③ myoclonic epilepsy:
④febrile seizures:
 (2)Partial
①Simple partial:
②Complex partial: *
4.treatment
(1) primary epilepsy
antiepileptic drugs.
(2) secondary epilepsy
antiepileptic drugs+against primary caus
e.
 (2)Partial
①Simple partial:
②Complex partial:
4.treatment
(1) primary epilepsy
antiepileptic drugs.
(2) secondary epilepsy
antiepileptic drugs+against primary caus
e.
 Phenytoin(dilantin)
【 pharmacokinetics 】
high concentrations in brain,
high plasma albumin binding,
half-life 24 hours.
【 mechanism of action 】
decreasing Na+ conductance in neurons s
tabilize nervous cellular membranes to re
duce the influx of calcium ions during depola
rization suppresses high-frequency repetit
ive firing halts seizure activity.
【 pharmacologic effects 】
1.antiepileptic effect: effective for tonic-clonic and
partial seizures.
2. Anti-peripheral neuralgia.
3. antiarrhythmia.
【 therapeutic uses 】
1. epilepsy. highly effective for all partial seizures, t
onic-clonic seizures and status epilepticus.not ef
fective for absence seizure.
2.peripheroneural pain. Trigeminal neuralgia, gloss
opharyngeal neuralgia and sciatic neuralgia etc..
3. arrhythmia (see antiarrhythmic drugs).
【 adverse effects 】
1.gastrointestinal irritation
administration with meal or after meal.
2. depression of CNS
3. blood dyscrasias
4. cardiovascular collapse
5. gingival hyperplasia
6. hepatitis in the long administration
7. allergic reaction
8. fetal malformation
9. to induce the P-450 system
 Barbiturates
1.characteristics
(1)mechanism of action is unknown but involves pot
entiation of the inhibitory effects of GABA neurons.
(2)Dose required for antiepileptic action is lower tha
n dosage that causes pronounced CNS depression
.more selectivity in anticonvulsant action than in se
dative effect.
2.use
(1)50% effective rate for simple partial seizure.
(2)not effective for complex partial seizure.
(3)first-choice drug for epilepticism in infant and child
ren.
(4)effective for recurrent tonic-clonic seizures especi
ally in patients who do not respond to diazepam pl
us phenytoin.
 Benzodiazepines
Intravenous diazepam is used for epile
pticism in adults.
Clonazepam is used for absence and
myoclonic seizure in children.
 Carbamazepine
1.The actions and mechanism are similar to
those of phenytoin.
highly effective for all partial seizure as f
irst-choice drug,
highly effective for tonic-clonic seizures,
effective for trigeminal neuralgia etc..
2.more adverse effects,especially serious liv
er toxicity.
 Ethosuximide
1.effective for absence seizure,
no effective on other seizures.
2.more adverse effects,in sensitive individua
ls a Stevens- Johnson syndrome and urtica
rria may occur. leukopenia, aplastic anemia
and thrombocytopenia may occur.
Sodium valproate
most effective for myoclonic seizure to r
educe incidence and severity of tonic-clonic
seizures,effective for absence seizure but s
econd choice because of its hepatotoxicity.
*
 CHAPTER 16 Anticonvulsant Drugs

1.pathogenesis
2.anticonvulsant drug
barbiturates, benzodiazepines, chloral h
ydrate and magnesium sulfate injection etc
.
 Magnesium sulfate
【 pharmacologic effects 】
ADMINISTRATION
1.oral administration
laxative effect and promoting bile excretion.
2. injection administration
(1)anticonvulsant
①inhibiting CNS by Mg2+,
②relaxation of skeletal muscle by antagonis
m of Ca2+ and inhibiting release of Ach from t
he end of motor nerve by Mg2+.
(2)hypotensive: direct vasodilation.
【 therapeutic uses 】
1. constipation, promoting excretion of toxic
substances and parasites in the intestinal t
ract.P.O.
2. convulsion and hypertensive emergencies
: injection.
【 adverse effects 】
breathe inhibition and hypotention, eve
n death.
Calcium chloride or calcium gluconate
should be administered.
CHAPTER 17 Agents Used in the Treatm
ent of Parkinsonian Disorders

1.classification of diseases
Parkinsonian disease
Parkinsonian syndrome.
 2.Pathogenesis
nigra caudatum
○ ○
DA Ach
striatum
(-) (+)
 
motor neurons in anterior horn of spinal cord
 
skeletal muscle contraction
3.therapy
reestablish dopamine/ acetylcholine balance.
(1)increase function of dopaminergic neurons
in the nigrostriatum,
(2)decrease function of cholinergic neurons.
4.classification of drug
(1)dopaminomimetic
levodopa, carbidopa ,amantadine
(2)anticholinergic drugs
trihexyphenidyl
 Levodopa(L-dopa)
【 mechanism of action 】
L-dopa is transformed to dopamine via dopa dec
arboxylase in the brain and corrects dopamine d
eficiency in nigrostriatum.
【 pharmacokinetics 】
1.Dopamine does not cross BBB, thus L-dopa is gi
ven instead and is readily transported into the C
NS.
2.L-dopa is well absorbed from the small intestine;
however, 99% is rapidly decarboxylated in the p
eriphery,resulting in peripheral side effects. So, l
arge dose of L-dopa is required. *
【 pharmacologic effects 】
1. The improvement of bradykinesia and rigidit
y is more rapid and complete than of tremor
.
2. L-dopa is more effective for young and mild
patients or early disease than old and sever
e patients.
3. L-dopa is ineffective for Parkinsonian syndr
ome induced by phenothiazides.
4. Tolerance to both beneficial and adverse eff
ects from levodopa occurs with time. L-dopa
is more effective in the first 2-5 years of ther
apy.
【 therapeutic uses 】
effective for Parkinsonian disease and P
arkinsonian syndrome caused by other cau
ses except phenothiazides.
The combination of levodopa with carbid
opa is recommended.
【 adverse effects 】
1.cardiovascular effects: tachycardia, arrhyth
mias etc.
2.central nervous side effects: vivid dream, d
elusion etc. mental disturbances.
3.gastrointestinal reaction:nausea, vomiting.
 Carbidopa
Carbidopa is an inhibitor of dopa decar
boxylase. Because it is unable to penetrate
BBB, it acts to reduce the peripheral conver
sion of L-dopa to dopamine. Carbidopa is u
sed in combination with L-dopa to augment
beneficial effects of L-dopa and to reduce d
ose and adverse effects of L-dopa.
 Amantadine
1.action mechanism
to improve Parkinsonian symptoms by stimulating th
e synthesis and release of dopamine from the survivi
ng dopaminergic nerve terminals and delaying its reu
ptake in the nigrostriatum.
2.effect
more effective than anticholinergic agents against r
igidity and bradykinesia, less effective than L-dopa in
the treatment of Parkinsonian disorders,no effective f
or tremor.
3.use
alone for early Parkinsonian disease; in combination
with L-dopa for various Parkinsonian diseases.
4.adverse effect
restlessness,agitation,confusion and hallucination.
 Trihexyphenidyl(Artane)
1.action mechanism: to block cholinergic receptors in
CNS to reduce the function of cholinergic nerves in
nigrostriatum to restore the balance between the d
opaminergic and cholinergic neurons.
2.effect: less efficaciou than levodopa.The effects on
tremor is more pronounced than effects on bradyki
nesia and rigidity.
3.use:alone for the mild patients, patients of the disc
ontinuation of L-dopa due to its adverse effects as
well as Parkinsonian syndrome induced by phenot
hiazides; in combination with L-dopa for any Parki
nsonian disorders.
4.side effects: similar to thoses of atropine.
CHAPTER 18 Agents used in the Treatmen
t ofPsychiatric Disorders

【 classification 】
1.antipsychotic agents
phenothiazines
2.antimanic and antidepressive agents lithium
carbonate
3.antianxiety agents
benzodiazepines
 I Antipsychotic Agents
(antischizophrenic drugs,major tranquilizers,
neuroleptic drugs)
1.use
schizophrenia and manic states of other
psychiatric disorders.
2.schizophrenia menifestation
delusions, hallucinations and thinking or
speech disturbances.
【 classification of drug 】
The neuroleptic drugs can be classified into fiv
e major classifications based on the structur
e of the drug.
1.phenothiazines chlorpromazine,fluphenazi
ne,promethazine, thioridazine etc.
2. benzisoxazoles: risperidone
3.dibenzodiazepines: clozapine
4.butyrophenones: haloperidol
5.thioxanthenes: thiothixene*
【 pathogenesis of schizophrenia 】
Relevance of pathogenesis of schizophrenia
with dopaminergic nerve in CNS:

1.DA increase in the brain of the patient

2.DR increase in the brain of the patient
3.function of dopaminergic neurons increases
4.promotion of DA release induces episode of
schizophrenia
5.blocking DR inhibit episode of schizophrenia
 Dopaminergic nervous pathway
1.limbic system- mesencephalic pathway
emotion
2.cortico- mesencephalic pathway
thinking and motion
3.nigrostriatum pathway
extrapyramidal reactions
4.hypothalamo-hypophysis pathway
endocrine
【 mechanism of action 】
antagonism of dopaminergic receptors(D2) i
n the CNS.
1.to block dopamine receptors in limbic system -
mesencephalic pathway to improve emotion
2.to block dopamine receptor in cortico- mesenc
ephalic pathway to restore thinking and motion
3.to block dopamine receptor in nigrostriatum pa
thway to cause extrapyramidal symptoms
4.to bock dopamine receptor in hypothalamo-hy
pophysis pathway to cause endocrine dysfunc
tion
 Phenothiazines
【 classification 】
Drug Major use Frequency of Adverse Effects
orthostatic extrapyramidal
hHypotension symptoms
chlorpromazine antipsychotic moderate moderate
(wintermin) antiemetic
clozapine antipsychotic low low 
anticholinergic 
antihistaminic
thioridazine antipsychotic moderate low
triflupromazine antipsychotic moderate high
fluphenazine antipsychotic low high
prochlorperazine antiemetic low low~moerate
promethazine antihistaminic moderate low
【 pharmacologic effects 】
1.effects on CNS
(1) antipsychotic effects
(2) sedation and synergism with other
CNS depressives
(3) antiemetic effects
(4) effects on temperature-regulating
mechanisms
2.altering endocrine
3.peripheral effects
1.effects on CNS
1) antipsychotic effects
(1)tranquilization: to make animals docile and
friendly, rapidly control manic states of
psychotic patients and make them
quiet(calming effect) and peaceful; make
patients feel indifferent, then induce sleep in
few days.
(2) restoration of intellect, emotional quieting
and reducing psychomotor excitement of the
patient in few weeks.
(3) to eliminate hallucination and illusion of the
patient in few months.
 action mechanism
antipsychotic effect via blocking dopami
ne D2 receptor in limbic system- mesencep
halic and cortico-mesencephalic pathways
.
2) sedation and synergism with other CNS d
epressives.
3) antiemetic effects:
to block D2 receptors in medullary CTZ. I
n high doses, the agents may directly depr
ess the medullary vomiting center.
4)effects on temperature-regulating mechani
sms:
to inhibit temperature-regulating center i
n hypothalamus to induce poikilothermia.
 2.altering endocrine
to depress the hypothalamus by blocking dopa
mine receptors to induce endocrine alteration with
lactation and gynecomastia, abnormal pigmentatio
n, decrease of corticotropin release and secretion
of pituitary growth hormone, weight gain and incre
ased appetite.
3. peripheral effects
orthoatatic hypotension and miosis by α-recepto
r blocking; blurred vision, constipation, dry mouth,
decreased sweating, mydriasis and rarely urinary r
etention by blockade of M receptors.
【 therapeutic uses 】
1.psychotic disorders
including mania, paranoid states, schizophrenia a
nd psychoses associated with chronic alcoholism
(alcoholic hallucinosis).
2.most phenothiazines except thioridazine are effe
ctive for nausea and vomiting. But, they are ineff
ective for vomiting induced by stimulating vestibu
les of ears.
3.artificial hibernation*
4.antipruritics:promethazine.
5. intractable hiccup: chlorpromazine.
Lyticcocktail and physical reduction of body temperatur
e
↓
body temperature↓+ central depression
↓
irritability to pathologic reaction↓;
basal metabolism↓→reduction of O2 consumption;
vasodilation→to improve microcirculation
↓
to protect the important organs from damage to g
ain enough time for effective etiological treatment by
other drugs. 
Artificial hibernation therapy can be used in seriou
s patients with toxic infection, intoxication and traum
a etc.
【 adverse effects 】
1.general adverse effects
2.extrapyramidal effects:
manifestation: Parkinsonian syndrome, acute dyst
onic reaction (facial grimacing and torticollis) and t
ardive dyskinesia(sucking and macking of the lips
and other involuntary facial movements).
pathogenesis: blocking DA receptors in the nigros
triatum.
treatment: artane.
3. cardiovascular effects: orthostatic hypotension, sy
ncope and reflex tachycardia.
4. allergic reactions.
II Mood-Altering Drugs (Antimanic and Anti
depressive Agents)
Pathogenesis of depression is thought to be rela
ted to deficiency of monoamines such as 5- HT and
noradrenaline in certain key sites of the brain. Mani
a would be induced by an overproduction of these
neurotransmitters. All clinically useful antidepressa
nt drugs directly or indirectly potentiate the noradre
naline, dopamine, and/ or serotonin in the brain.
Depression is classified into 3 types:
major (endogenous)
reactive
bipolar(manic-depressive)
 Antimanic agents—lithium carbonate
【 mechanism of action 】
The mechanism of action is unknown. It is
currently proposed that lithium acts by alterin
g the cellular concentration of the second me
ssenger inositol triphosphate (IP3).
【 therapeutic uses 】
1.mania and manic episodes of bipolar disorde
r
2.useful in reducing the intensity of depression
【 adverse effects 】
high toxic and low therapeutic index,to maintain s
erum concentration between 0.8 and 1.5mmol/L.
toxic effects:
ataxia,tremors,convulsion,anorexia, vomiting, d
iarrhea, excessive thirst and polyuria,somnolene, c
onfusion and psychomotor disturbances, cardiova
scular anomalies in the newborn, hypotension and
cardiac arrhythmias. Chronic lithium use can result
in thyroid enlargement.
Lithium intoxication can usually be reversed by
osmotic diuresis or, in more severe cases, by dialy
sis.
 Antidepressants agents
【 classification 】 *
1.tricyclic or polycyclic antidepressants imipramin
e, amitriptyline, desipramine, nortriptyline, doxep
in,trimipramine.
2. MAO inhibitors
(1) Hydrazides: isocarboxazid,phenelzine
(2) Nonhydrazides: tranylcypromine
3.selective 5-HT reuptake inhibitors
fluoxetine, sertraline, paroxetine, bupropion, ven
lafaxine ect.
 Tricyclic/ polycyclic antidepressants
【 mechanism of action 】
to block NA and 5-HT reuptakes into the
presynaptic neurons to increase NA and 5-
HT level in the synaptic cleft in the CNS.
monoamine receptor densities in the brai
n may change over 2 to 4 week with drug u
se and may be important in the onset of act
ivity.
【 pharmacokinetics 】
well absorbed upon oral administration,
widely distributed,
readily to penetrate into the CNS,
long half-lives,
low and inconsistent bioavailability because
of variable first pass metabolism in the liver.
Therefore the patient response is used to
adjust dose.The initial treatment period is typi
cally 4 to 8 weeks.The dose can be gradually
reduced unless relapse occurs.
【 pharmacologic effects 】
All the tricyclic antidepressants have si
milar therapeutic efficacy.
1. effects on CNS
2.cardiovascular effects
3. effects on autonomic nervous system
1. effects on CNS
(1)A nondepressed person experiences sleepiness a
fter administration. In addition, anxiety and toxic an
ticholinergic effects may be experienced.
(2)In the depressed patient, tricyclic antidepressants
elevate mood, improve mental alertness, increase
physical activity and reduce morbid preoccupation.
The onset of the mood elevation is slow and requir
es 2 to 3 weeks after administration begins. The lat
ency period can be as long as 4 weeks.
(3)Tricyclic antidepressants can cause extrapyramid
al symptoms and ataxia. High doses of tricyclic ant
idepressants are capable of producing seizures an
d coma.
2.cardiovascular effects
orthostatic hypotension, arrhythmias, tachycardia,
slow atrioventricular conduction.
3. effects on autonomic nervous system antich
olinergic effect.
【 therapeutic uses 】
1. severe endogenous depression.
2. Enuresis(bed-wetting): imipramine.
3. Obsessive-compulsive neurosis accompa
nied by deprssion, and phobic anxiety syndr
omes, chronic pain, and neuralgia may resp
ond to tricyclic agents.
【 adverse effects 】
The adverse effects of tricyclic anti-depres
sants resemble to phenothiazines.
1.peripheral effects
anticholinergic action
2.central effects
ataxia, dizziness and muscle tremor; mani
c excitement and delirium can occur in the p
atients with bipolar illness.
3. cardiovascular effects
cardiac arrhythmias and hypotension
 Differentiation of tricyclic antidepressants
drug t1/2(h) inhibition of reuptake sedation anticholinergic
of monoamines
5-HT NA
imipramine 9~24 ++ ++ ++ ++
desipramine 14~76 0 +++ + +
amitriptyline 17~40 +++ + +++ +++
doxepin 8~24 weak weak +++ +++
 MAO inhibitors

MAO inhibitors inhibit MAO activity to inc

rease store of noradrenaline, serotonin and
dopamine within the neuron.
MAO inhibitors are indicated for depressi
on patients who are unresponsive or allergi
c to tricyclic antidepressants or who experi
ence strong anxiety.
 Selective 5-HT reuptake inhibitors*

The selective 5-HT reuptake inhibitors

specifically inhibit serotonin reuptake. C
ompared with tricyclic antidepressants, the
se drugs cause fewer anticholinergic effect
s and lower cardiotoxicity.
 III Agents Used in the Treatment of Anxiety
(anxiolytic drugs or minor tranquilizers)
1.anxiety: sydrome , anxiety sydrome
2.use: anxiety or neurosis.
3.characteristics
sedative
hypnotic properties
central skeletal muscle relaxant activity habitu
ation and physical dependent liability lower in
cidence of adverse effects than the
antipsychotic agents.*