1. Name an example of each of the 3 phenothiazine sub-families and state how they differ from one another in terms of potency and side effects.

• Aliphatic side-chain: Chlorpromazine
• Piperidine side-chain: Periciazine 
• Piperazine side-chain: Fluphenazine

Aliphatic and piperidine compounds have a low potency, little EPS, severe sedation, strong anti-cholinergic effects, strong alpha-lytic effects (postural hypotension) and are cardiotoxic. 

Piperazine compounds have a high potency, more EPS, weaker anti-cholinergic effects, weaker alpha-lytic effects, less sedation and less cardiovascular side effects. 

 

2. Which receptors in particular are blocked by the typical antipsychotic drugs?

Typical antipsychotics block the mesolimbic D2 receptors, and to a lesser extent, they also block H1 receptors, cholinergic receptors and alpha-1 adrenergic receptors. 

 

3. How does the mechanism of action of the atypical drugs differ from that of the typical drugs?

Atypical drugs have a higher affinity for serotonin receptors. Atypical drugs block the 5HT2a receptors more than the D2 receptors. Typical antipsychotics on the other-hand have a higher affinity to block D2 receptors.

 

4. Which of the receptors blocked by older drugs reduce the risk of EPS?

Typical drugs (Benzamides) have a lower risk of EPS due to localisation of the D3 receptors.

 

5. Which of the receptors blocked by the older drugs have a high incidence of extrapyramidal side-effects? What is the reason for this?

Haloperidol is a typical antipsychotic and has a very high binding affinity for the blockade of D2 receptors. It has a very high potency and therefore results in severe extra-pyramidal symptoms. 

 

6. Because of which receptor(s) blockade do the aliphatic group of drugs have a high incidence of autonomic side effects? 

The blockage of cholinergic (muscarinic) receptors.