Ch12: Antipsychotic Drugs

Question 1

Brain structural & functional abnormalities in schizophrenia

Answer 1

• Lateral & third ventricles are twice as large
• Less brain tissue volume, esp in corpus callosum, cerebellum, frontal and temporal lobes, limbic system (amygdala, hippocampus, cingulate gyrus)

Question 2

Dopamine hypothesis of schizophrenia

Answer 2

Schizophrenia/psychosis result from excessive dopamine activity, specifically at D2 receptors
- Most effective antipsychotics are those with high affinity for D2 receptors

Question 3

Glutamate hypothesis of schizophrenia

Answer 3

Glutamate dysfunction is the result of two combined processes:

1) NMDA receptor hypoactivity
2) AMPA receptor hyperactivity

• NMDA antagonists mimic positive and negative symptoms of schizophrenia
• Progressive loss of glutamate synapses, resulting in NMDA receptor hypoactivity

Question 4

What is the shared property of atypical antipsychotics?

Answer 4

1) Very weak affinity for the D2 receptor
- They bind to D2 receptors very loosely and have dissociation constants that are significantly higher than that of dopamine or the typicals
- Bc of their weak affinity, they avoid the problem of blocking dopamine in the nigrostriatal system, thus produce far fewer EPS (alterations in movement like Parkinson’s)

2) High affinities for D3 and D4 receptors
- Neither is found in basal ganglia

3) 5-HT2A blocking ability
- This activity is much higher for atypicals