• 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.

There are 3 sub-families which is primarily based on the side chain:

1. 1. Aliphatic side chain: Chlorpromazine
   2. Piperidine side chain: Periciazine and Thioridazine
   3. Piperazine side chain:  Fluphenazine, Perphenazine, Trifluoperazine, Prochlorperazine.

Aliphatic and piperidine compounds:

• Low potency thus little EPS
• Severe sedation
• Strong anti-cholinergic effects
• Strong α-lytic effects
• Cardiotoxic

Piperazine compounds:

• Higher potency thus more EPS
• Less sedation
• Less anti-cholinergic effects
• Less α-lytic effects
• Less cardiovascular side effects

• Which receptors are blocked by the typical antipsychotic drugs?

The D2 receptors in the mesolimbic pathway.

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

Atypical drugs have a higher affinity for 5-HT_2A receptor thus they block more serotonergic receptors than D2 receptors and it also blocks M1, H1 receptors, whereas typical drugs only block D2 receptors in the mesolimbic pathway.

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

Benzamides block both D2 and D3 receptors but the risk of EPS are reduced due to the localisation of D3 receptors in the limbic area.

Aliphatic compound also tends to have a lower potency thus have less EPS.

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

Extrapyramidal side effects are known to be caused by the blockade of D2 receptors in the nigrostriatal pathway, therefore drugs that block D2 receptors cause EPS.

Drugs known to cause EPS is the piperazine derivatives due to their high potency thus extensively blocking D2 receptors.

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

Autonomic side effects are caused by the blockage of alpha and cholinergic (muscarinic) receptors in the sympathetic and parasympathetic nervous systems