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

1. Aliphatic sidechain: Chlorpromazine
2. Piperidine sidechain: Periciazine
3. Piperazine sidechain: Fluphenazine, Perphenazine, Trifluoperazine, Prochlorperazine.

Aliphatic and piperidine compounds:

• Low potency*, little EPS
• Severe sedation
• Strong anti-cholinergic effects,
• Strong α-lytic effects (postural hypotension), 
• Cardiotoxic

Piperazine derivatives:

• High potency, more EPS,
• Weaker anti-cholinergic side effects  
• Weaker α-lytic effects,
• Less sedation
• Less cardiovascular (CVS) side effects

 

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

Mesolimbic D2 Receptors

 

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

Atypical drugs : block 5-HT_2A receptors more than D₂. 

Typical drugs: block mesolimbic DA 2 receptors.

 

• Which of the receptors blocked by the older drugs reduce the risk of extrapyramidal side effects?

Benzamides block D₂ (selectively) and D₃ receptors. The risk of extra pyramidal side effects is reduced due to the limbic localisation of the D₃ receptors. Furthermore, Aliphatic side-chain typical drugs such as Chlorpromazine compounds have a low potency and few extra pyramidal side effects

 

• Which of the older drugs have a high incidence of extrapyramidal side effects? What is the reason for this?

Extrapyramidal side effects are caused by the blockade of D2 receptors in the nigrostriatal pathway which occurs potently by drugs of the piperazines derivatives.

 

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

Autonomic side effects occurs as a result of Muscarinic and α1 blockade effects.