Pharmacology. 05/03/20
Antipsychotic Drug
1. Outline
What is schizophrenia?
Pathways involved
- Dopamine theory
- Glutamate
- Glu/GABA
Side effects
- How receptor properties of antipsychotics ameliorate side effects?
2. Schizophrenia
‘Is a disorder of the mind that affects how you think, feel and behave.’ RCPsych
‘Positive’ clinical features, increase in dopamine
- Delusions –ideas of reference
- Hallucinations –voices
- Thought disorder –disconnected/wanders
- Abnormal, disorganised behaviour –disorientation, aggression
- Catatonia –immobility, purposeless activity
‘Negative’ clinical features, decrease dopamine
- Withdrawal
- Emotional flattening
- Anhedonia–loss of experiencing pleasure
Cognitive defects (resistant to antipsychotics)
- Premature dementia
- Depression & anxiety
1% of population
- 1:10 with schizophrenia have a parent who suffers, can be miss diagnosed with bipolar
- ♀=♂, common onset 15-35yrs old
Up to 50% attempt suicide
Genetic causes
- ˃100 susceptibility genes reported
- Most robust associations control neuronal development, synaptic connectivity & Glu-ergic
transmission
o Neuregulin (neuronal plasticity, neuronal expression), NOTCH-4, TCF-4
Environmental causes
- Maternal viral infections
- Cannabis use
, Pharmacology. 05/03/20
Antipsychotic Drug
In mesolimbic there
are more D2 and in
mesocortical there are
more D1. It’s not that
DA has more affinity
for one or another
3. Dopamine theory
Amphetamine-induced DA release (Carlson, 2000)
- behaviour akin to acute schizophrenic episode
L-dopa & DA agonists –Parkinson’s disease
- hallucinations
DA antagonists control positive symptoms (over activation of D2 receptors in the mesolimbic
pathways.
- block amphetamine-induced effects
Amphetamine is a substrate for DAT and competes with
DA to be taken up into the cell and for the vesicle transport.
Amphetamine can be taken up into vesicles and facilitate
the release of DA, cytoplasmic DA increases therefore DA
would get reverse
4. Glutamate –negative symptoms
↓vesicular glutamate transporter (VGluT), less
glutamate can lead with it being broken down rather
than being released inti the synapse.
↓Glu= ↓NMDA activation
↓DAergic activity mesocorticol pathway
↓[DA] in PFC = negative symptom
Antipsychotic Drug
1. Outline
What is schizophrenia?
Pathways involved
- Dopamine theory
- Glutamate
- Glu/GABA
Side effects
- How receptor properties of antipsychotics ameliorate side effects?
2. Schizophrenia
‘Is a disorder of the mind that affects how you think, feel and behave.’ RCPsych
‘Positive’ clinical features, increase in dopamine
- Delusions –ideas of reference
- Hallucinations –voices
- Thought disorder –disconnected/wanders
- Abnormal, disorganised behaviour –disorientation, aggression
- Catatonia –immobility, purposeless activity
‘Negative’ clinical features, decrease dopamine
- Withdrawal
- Emotional flattening
- Anhedonia–loss of experiencing pleasure
Cognitive defects (resistant to antipsychotics)
- Premature dementia
- Depression & anxiety
1% of population
- 1:10 with schizophrenia have a parent who suffers, can be miss diagnosed with bipolar
- ♀=♂, common onset 15-35yrs old
Up to 50% attempt suicide
Genetic causes
- ˃100 susceptibility genes reported
- Most robust associations control neuronal development, synaptic connectivity & Glu-ergic
transmission
o Neuregulin (neuronal plasticity, neuronal expression), NOTCH-4, TCF-4
Environmental causes
- Maternal viral infections
- Cannabis use
, Pharmacology. 05/03/20
Antipsychotic Drug
In mesolimbic there
are more D2 and in
mesocortical there are
more D1. It’s not that
DA has more affinity
for one or another
3. Dopamine theory
Amphetamine-induced DA release (Carlson, 2000)
- behaviour akin to acute schizophrenic episode
L-dopa & DA agonists –Parkinson’s disease
- hallucinations
DA antagonists control positive symptoms (over activation of D2 receptors in the mesolimbic
pathways.
- block amphetamine-induced effects
Amphetamine is a substrate for DAT and competes with
DA to be taken up into the cell and for the vesicle transport.
Amphetamine can be taken up into vesicles and facilitate
the release of DA, cytoplasmic DA increases therefore DA
would get reverse
4. Glutamate –negative symptoms
↓vesicular glutamate transporter (VGluT), less
glutamate can lead with it being broken down rather
than being released inti the synapse.
↓Glu= ↓NMDA activation
↓DAergic activity mesocorticol pathway
↓[DA] in PFC = negative symptom
