Antipsychotic Agents

Conventional Antipsychotic Drugs

Some important
Chlorpromazine notes:
Mesolimbic
Fluphenazine positive symptoms

Haloperidol Mesocortical
negative symptoms
etc and cognitive
Conventional Nigrostriatal
Antipsychotic Drug extrapiramidal
D2 antagonist, symptoms
muscarinic-cholinergic Tuberoinfundibular
antagonist, alpha-1 prolactin
adrenergic antagonist, secretion
Haloperidol histamine-1 antagonist
 Mechanism of Action
Dopamine 2 reseptor antagonist
Mesocortical pathway

Increase in
negative
and
cognitive
Mesolimbic pathway
symptoms
block positve symptoms Pure D2
Blocker
Nigrostriatal pathway

Long-term blockade

EPS

Tuberoinfundibular pathway Up-regulate tardive dyskinesia

Pure D2
Prolactin Blocker
levels rise
Clinical uses of Conventional/Typical Antipsychotics

Positive symp Emergency, 2nd line,noncompliant

Aggressive symp Emergency, 2nd line
Atypical Antiphysicotic Agents
From a pharmacological perspective,the
atypical antipsychotic as a class may be
defined in part as serotonin-dopamin
antagonists (SDAs)
Blockade of serotonin 2A
(5HT2A)receptors, as well as blockade of
dopamin 2 (D2) receptors.
 Three pharmacologic and clinical criteria :
1. atypical antipsychotics have serotonin
2A-dopamine 2 antagonist
2. atypical antipsychotics cause fewer
EPS
3. atypical antipsychotics improve positive
symptoms
Serotonin-Dopamin Interactions
Serotonin inhibits dopamine release, at the level
of dopamine cell bodies and dopaminergic axon
terminals . Serotonin neurons from the
brainsterm raphe innervate dopamine cell
bodies in the substansia nigra.
Serotoniergic innervation the substansia
nigra,axon terminals arriving from raphe synaps
and dendrites dopaminergic cells (fig.11-18
 Serotonin 2A antagonism reverses dopamine 2
antagonism stimulating 5HT2A receptors inhibits
dopamine release (fig.11-22)
Atypical antipsychotic via blockade of 5HT2A
receptors,allows the extra dopamine to compete
with the atypical antipsychotic to reverse
blockade D2 receptors (fig.11-24)
 Dopamine deficiency in mesocortical dopamine
pathway is to be one causes the negative
symptoms schizophrenia (fig.11-27)
Blockade of 5HT2A receptors with an atypical
antipsychotic should lead to dopamine
release,which could compensate dopamine
deficiency and improve negative symptoms
 Atypical antipsychotics undoubtredly cause far
fewer EPS
Atypical antipsychotics reduce negative
symptoms of schizophrenia
Atypical antipsychosis reduce affective
symptoms in schizophrenia
Atypical antipsychotics may reduce symptoms
and related disorder such as Alzhaimers
disease