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. 

1. Aliphatic side-chain – Chlorpromazine 

2. Piperidine side-chain – Periciazine 

3. Piperazine side-chain – Fluphenazine 

Chlorpromazine and Periciazine have a low degree of potency and little EPS, whereas Fluphenazine has a higher potency and more EPS. 

Chlorpromazine- and Periciazine’s side effects include:

• Severe sedation

• Anti-cholinergic effects

• Strong alpha-lytic effects (postural hypotension) 

• Cardiotoxicity 

Whereas, Fluphenazine causes less sedation and cardiovascular side effects, and weaker anti-cholinergic side effects & -α-lytic effects. 

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

• Mesolimbic D2 receptors

• 5-HT2A receptors

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

The typical antipsychotic drugs are multi-potent competitive antagonists that block DA, M, alpha, histamine and 5-HT receptors. Whereas, atypical drugs are multi-potent antagonists that have a higher affinity for 5-HT2 receptors than DA receptors and they have less EPS, prolactin effects and TD. D2 blockers, Clozapine has marked D4 blocking effects and strong M1, H1 and α1-blocking effects. Risperidone and paliperidone increase prolactin as the older drugs do, more EPS as well. 

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

Dopamine-2 receptors. 

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

• Haloperidol (a butyrophenone derivative) – due to its potent antagonistic effects on D2 receptors, it has a proven high prevalence of EPS. 

• Piperazine derivatives – due to their high potency they have a strong antagonistic effect on D2 receptors that causes EPS. 

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

Blockade of alpha-1 receptors and also the blockade of cholinergic receptors (Muscarinic receptors) cause autonomic side effects.