Chapter 18

Psychopharmacologic Drugs

Classification of drugs

Antipsychotic Agents
Antimanic drugs
Antidepressant drugs

mechanism of action of antipsychotics

Blockade of the dopamine receptors in the
mesolimbic and mesocortical areas in the brain.
Blocking of the serotonin receptors:
clozapine( )
The mechanism of the main adverse effects is
blackade of the dopamine receptors in the
tuberoinfundibular nigrostriatal
areas.

Several important dopaminergic pathway

Several important dopaminergic pathway are now
recognized in the brain.
(1)The first pathway the one most closely related to
behavior is the mesolimbic-mesocortical pathway.
(2) Nigrostriatal pathway, involving in the coordination
of voluntary movement.
(3) tuberoinfundibular pathway.
The antipsychotic agents block D2 receptors
stereoselectively, for the most part,and their binding
affinity is very strongly correlated with clinical
antipsychotic potency.

Antipsychotic Agents

Classification of Antipsychotic Agents

Typical Antipsychotic drugs :

Phenothiazines
Chlorpromazine(

Atypical Antipsychotic drugs :

Clozapine and risperidone
Sulpiride

Antipsychotic Agents

Chlorpromazine(
[Pharmacological effects]
Chlorpromazine can block a number of receptors.
These receptors include dopamine(DA) and alphaadrenoceptor, muscarinic, H1 histaminic
receptors(DA , , M , H1 receptors)
Of these receptors, the dopamine receptor effects
quickly became the major focus of interest.
Chlorpromazine proved to have a wide variety of
central nervous system,autonomic,and endocrine
effects.

Chlorpromazine

[Pharmacological Effects]

1.Sedative and anti-antianxiety effects

Antipsychotic drugs possess calming effect and
lower spontaneous physical movement.

2.Effects on Conditioned response

Antipsychotic drugs selectively inhibit the ability of
animals to make a conditioned avoidance response.

Chlorpromazine

[Pharmacological Effects]

3.General psychophysiological effects

After given drugs,psychotic patients initially may
become somewhat slow in response to external
stimuli and drowsiness,and then the patients
become less agitated,aggressive and impulsive
behavior diminishes, and gradually,symptoms of
hallucinations ,delusions ,and incoherent
thinking tent to disappear.

[Pharmacological Effects]

Chlorpromazine

4.Effects on chemoreceptor trigger zone (CTZ)

Chlorpromazine can block apomorphine-induced vomiting.
This action is due to dopamine receptor blockade, both
centrally(in the chemoreceptor trigger zone of the medulla)
and peripherally(on receptors in the stomach). However, large
doses of chlorpromazine may depress the vomiting center
directly.
5.Effects on body-temperature regulation
The chlorpromazine depress temperature-regulating
mechanisms. It may produce hypothermia or hyperthermia,
depending on the environmental temperature.

Chlorpromazine

[Pharmacological Effects]
6.Effects autonomic nervous system
Chlorpromazine can block alpha-receptor, converting a
pressor of epinephrine.
Otherwise, chlorpromazine can depresses vasomotorstabiling center and dilates directly blood vessels.
In addition,chlorpromazine also block the muscarinic
actions of acetylcholine.

[Pharmacological Effects]

Chlorpromazine

7.Effects on endocrine system

More prolactin releasing induces lactation;
Inhibiting corticotropin-releasing hormone(CRH)
release which results in decreased release of
glucocorticoids;also impairing glucose tolerance and
insulin release.
8.Potentiation of other central depressive agents
Antipsychotic drugs potentate the effects of sedatives,
analgesics, antipyretic-analgesics and general
anesthetics.

Chlorpromazine

Therapeutic Uses
1.Treatment of Schizophrenia
2.Prevention of nausea and vomiting caused by
drugs and radiation sickness.
3.Hibernation therapy
chlorpromazine + promethazine +
pethidine

[Adverse
Reactions]

Chlorpromazine

1.Extrapyramidal Reactions :
(1) Parkinsons syndrome;
(2) Akathisia( );
(3) Dystonic reactions ( )
These acute extrapyramidal reaction can be treated
with antimuscarinic drugs, artane.
(4) Tardive dyskinesia
It has been proposed that it is caused by a relative
cholinergic deficiency secondary to supersensitivity
of dopamine receptors.

Chlorpromazine

[Adverse
Reactions]
2.Behavioral effects
include toxic psychosis
3. Adverse effects on autonomic nerve system
Orthostatic hypotention
Dry mouth
Tachycardia
Blurred vision

Drugs used disorders Antidepressant

Nonspecific reuptake inhibitors(NE,5-HT,DA)

imipramine Tricyclic Antidepressants
Selective serotonin-reuptake inhibitors (5-HT)
fluoxetine ( )
Mono-amine oxidase(MAO) inhibitors
Atypical antidepressants
Mirtazapine increases the concentration of 5-HT and
NE in the nerve ending by blocking the presynaptic
negative feedback receptors.

Imipramine

[Pharmacological
Effects]

Tricyclics antidepressants block the amine

(norepinephrine or serotonin) reuptake pumps. Such
an action presumably permits a longer sojourn
of neurotransmitter at the receptor site.
(The pathogenesis of depression- the AmineHypothesis)

[Clinical Uses]
1. The major indication for these drug is to treat
depression.
2. Enuresis
3. Anxiety and phobia

Adverse effects of Tricyclics antidepressants

Sedation

Sleepiness,additive effects with other

sedative drugs

Sympathomimetic

Tremor, insomnia

Antimuscarinic
hesitancy.

Blurred vision, constipation, urinary

Cardiovascular

Orthostatic hypotension,conduction defects,

arrhythmias

Neurological

Seizures

Endocrine

Weight gain.

Antimanic Drugs
Lithium salts
This drug may decrease norepinephrine and
dopamine release. These effects might be relevant to
its antimanic action.
Lithium salt counteracts mood changes without
producing sedation.
Phenothiazines have calming and depressant effects
which are useful in controlling all kinds of mania
,but do not normalizing behavior.