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Psychotropic drugs
Liming Zhou (周黎明)
Department of pharmacology
Classification
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Antipsychotic Drugs
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Antimanic drugs
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Antidepressants
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anxiolytics
Antipsychotic Drugs
Contents
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Overview
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Inreuduction of Schizophrenia
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Classification of antipsychotic drugs
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Chlorpromazine
Overview
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Antischizophrenic,neuroleptic drugs
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These agents are prescribed for
treating schizophrenia or
management of psychotic symptoms
Overview

What is schizophrenia ?
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There appears to be a genetic
component to schizophrenia.
There is also evidence for changes in
brain structure.
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Schizophrenia
schizophrenia
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Clinical Manifestations
Characteristics-- perturbations affecting:
language
perception
thinking
volition
Behavior
social activity
size of ventricles
Schizophrenia
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Syndrome overview:
Typically begins in late adolescence
Insidious onset.
Poor outcome.
Social withdrawal /perceptual
distortions lead to chronic delusions
（错觉）/hallucinations （幻觉）.
Schizophrenia
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Positive Symptoms:
Conceptual disorganization
Delusions
Hallucinations
Schizophrenia
Negative Symptoms:
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Anhedonia (快感缺乏)
Decreased emotional expression
Impaired concentration
Diminished socialization
Classification of antipsychotic
drugs

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Phenenothiazines（吩噻嗪类)
(Chlorpromazine)
Thioxanthenes(硫杂蒽类）
(Tardan,flupenthixol)
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Butyrophenones（丁酰苯类）
(Haloperidol)
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Atypicals )( 非 典 型 药 物 ）
(Clozapine)
Chlorpromazine (wintermine)
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Pharmaciolgical effects
CNS effects
1.neuroleptic effect:
hallucination and delusions（错觉）
improvement
Mechanism of action
Blockade dopaminergic
neurotransmission
-the limbic
- nigrostriatal
- hypothalamic system.
Dopamine Hypothesis:
This idea was suggested by observation that
drugs which reduced dopaminergic
activity reduced acute symptoms/signs of
psychoses.
 Symptoms notably Decreased - agitation
 anxiety
 hallucinations
Four pathway of dopaminergic
neurotransmission
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1)Mesolimbic-mesocortical
pathway
(one
most closely related to behavior )
2)nigrostriatal pathway(it is involved in the
coordination of voluntary movement)
3)tuberoinfundibular
pathway
(inhibits
prolactin secreation)
4 ） medullary-periventricular pathway (the
function is not clear ,may be involved eating
behavior)

Dopamin receptor: two type, five
subtype
- DA1 (D1-like receptor): D1,D5
- DA2 (D2-like receptor): D2,D3, D4
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D2 like receptors (D2, D3, D4)
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Activate Gi  cAMP
Block Ca++ channels
Open K+ channels
D2: putamen(壳核）, olfactory tubercle
（嗅结节）
D3: frontal cortex, medulla, midbrain
D4: ???
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D2 receptor activation  motor
activity  aggravates schizophrenia
D2 receptor blockade  alleviation of
schizophrenia
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Neuroleptic effect: blocking DA2
Side effect
(extra-pyramidal
blocking DA2
symptoms.):
Pharmalogical effects
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Antiemetic effect.
-This is a results of blocking DA2
receptor.
-In low doses, blocking DA2 receptor
in chemoreceptor trigger zone(CTZ).
-In high doses, chlorpromazine may
directly
depress
the
medulla
vomiting center.
Pharmalogical effects
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Altering
temperature-regulating
mechanisms.
in a cold climate it decrease
temperature in body
in a hot climate they can cause
hyperthermia
Pharmalogical effects
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Sympathetic
and
parasympathetic
nervous system effect:
-Blocking α-adrenergic receptor  Orthostatic
hypotension.
-Blocking M-receptor.
Blurred vision
Constipation
Dry mouth
Decreased sweating
Pharmalogical effects
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Endocrine system effect
Increasing the lactogenic hormone( 催 乳
素).Increased levels of prolactin may lead to
galactorrhea （溢乳).
phenothiazines decrease FSH and ACTH.
Decreasing release and secretion of pituitary
growth hormone.
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Prolactin
FSH
ACTH
growth hormone.
Therapeutic uses
 1. Psychotic disorders, all kind of
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schizophrenia.
2. Nausea and vomiting.(except
carsickness).
3. Decrease the temperature.
4. Control of intractable hiccup（呃逆打
嗝).
5.Therapy gigantism(巨人症).
untoward effects
(1) Special side effect:
Extrapyramidal symptoms
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A. Parkinsonian syndrome: the patients
display rigidity(僵化)and tremor
B. Acut dystonia: patients display facial
grimacing (面部的歪扭,) torticollis(斜颈)
C.Akathisia (静坐不能)
D. tardive dyskinesia (迟发性运动障碍）

patient display sucking of the lips and
other involuntary facial movement. (The
dyskinesia may persist for after
discontinuation of the therapy).
Untoward effects
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(2)General side effect:
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A. CNS depression
B. M-receptor blocking: The
symptom of M- receptor blocking
C. Orthostatic hypotension
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Untoward effects
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(3)Inducing psychosis by drug
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(4)seizure and epilepsy
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(5)allergic reaction
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(6)cardiovascular effect
Untoward effects
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(7)Endocrine disorder:
Hyperprolactinemia--causes:
For women: Amenorrhea(abnormal
suppression or absence of menstrual
flow), galactorrhea , infertility
For men: impotence infertility,diminished
libido
For children: decreasing growth.
Drug interaction:
1)Increasing CNS inhibition with ethanol,
sedative-hypnotics, morphine.
2)Inhibiting the of L-Dopa (agonist of the
doparmin-receptor).
3)Increase the dose with phentoin and
carbamazepine.
Atypical antipsychotic drugs
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Clozapine and Risperidone selectively inhibit
D4 and 5-HT2-receptors.
Risperidone selectively inhibit D2 and 5-HT2receptors.
Sulpiride selectively inhibit D2-receptors in
the mesolimbic and mesocortical areas of the
brain.
Sulpiride ,Clozapine and risperidone have low
risk of extra-pyramidal adverse reaction.
Atypical antipsychotic drugs
Sulpiride
 Selectively inhibit D2-receptors in the
mesolimbic and mesocortical areas of
the brain.
 Producing low extra-pyramidal adverse
reaction.
Antimanic drug
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Lithium carbonate
Pharmacodynamics
Possible mechanisms of action:
-effects on electrolyte/ion transport
neurotransmitter
-neurotransmitter release modulation
influence on second messengers.
Lithium salts how to affect second
messengers?(learning by yourself)
Antidepressants
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Overview
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Classification
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TCA Antidepressants
Overview
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Depression is an alteration of mood
characterized by sadness, worry, and
anxiety.
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The patient may suffer from losses of
weight, libido, and enthusiasm.
Depression
Clinical depression is a syndrome that may
include:
 Sustained mood disturbances
 Impaired memory and concentration
 Disturbed sleep
 Reduced energy level
 Reduced libido
 Impaired sleep.
Depression
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Patient complaints suggestive of
depression may include:
Pain (headaches, body aches)
A mood of apathy, anxiety, or
irritability
Sexual complaints
low energy, excessive tiredness
reduced capacity for enjoyment.
Classification of
Antidepressant Drugs
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Five of antidepressant
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Tricyclic antidepressants (TCA)
Monoamine oxidase inhibitors (MAO)
NA reuptake inhibitors
Serotonin-specific reuptake inhibitors
(SSRIs)
Serotonin and NA-specific reuptake
inhibitors
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Most antidepressants are believed to
improve by increasing NT
 Catecholamine
 5-HT stores
Tricyclic antidepressant TCAs
Imipramine
Pharmalogic effects
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CNS
-In the depressed patients , an
elevation of mood occur 2-3 weeks
after administration begins, the
latency period can be as long as 4
weeks.
-The imipramine blocks the re-uptake
of serotonin and NA
Pharmalogic effects
Autonomic nervous system
Blocking m-receptor
Pharmalogic effects
Cardovascular effect:
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Hypotensin (blocking α receptor)
Tachycardia
Mechanism of TCA:
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Blocking re-uptake of
neurotransmitter
Norepinephrine(NA)
Serotonin(5-HT)
Clinic use
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1)Therapy depression
2)Therapy enuresis
3)Therapy anxiety and phobicanxiety syndromes
4)Obsessive-compulsive neurosis
companied by depression
Untoward effects
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1)anticholinergic effect
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2)cardiac arrhythmas
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3)manic excitement can occur in
patient with bipolar manic-deprssive
illness
Untoward effects
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4)The combination of a MAO inhibtor
with tricyclic antipressants should
not be avoided ,since hyperpyrexia,
convulsions and coma can result
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Selective serotonin
inhibitors
A.Fluoxrtine
B.Paroxrtine
reuptake
Home work
Suggested further readings
Rojas-Corrales,MO.and Mico JA.
Antipressant-like effects of
tramadol and other central
analgesics with activity on
monoamines reuptake, inhelpless
rats.life science.2002,72(2):143152

1.How are agents in this chapter
classified?
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2.Describe
the
pharmacological
effects of Chlorpromazine.
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What are the major differences between
the TCA and SSRIs?