1. 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.

Phenothiazine Derivative	Example	Potency	Side effects
Aliphatic side chain	Chlorpromazine	Low potency	Little Extra pyramidal side effects Severe sedation Strong ant-cholinergic effects Strong α-lytic effects= postural hypotension Cardiotoxic
Piperidine side-chain	Periciazine	Low potency	Little Extra-pyramidal side effects Severe sedation Strong ant-cholinergic effects Strong α-lytic effects= postural hypotension Cardiotoxic
Piperazine side-chain	Fluphenazine, perphenazine, trifluoperazine, prochlorphenazine	High potency	More Extra Pyramidal side effects Weaker anti-cholinergic side effects Weaker α-lytic effect Less sedation Less CVS side effects

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

The Mesolimbic D2 Receptors are particularly blocked by typical APD’s  

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

Atypical drugs: Multipotent antagonists/inverse agonists. They have a higher affinity for 5-HT2 receptors. They Block 5-HT2A Receptors more than D2 Receptors

Typical Drugs: Block mesolimbic D2 Receptors

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

Dopamine-2 receptors reduces the risk of Extra pyramidal side effects

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

Piperazine Phenothiazine derivatives ( Fluphenazine, perphenazine, trifluoperazine, prochlorperazine): Potent D2 blockade

Butyrophenone derivatives (Haloperidol): Potent D2 blocker

Extra-pyramidal side effects are caused by D2 blockade in the Nigrostriatal pathway, therefore drugs that are potent D2 blockers will lead to EPS even at very low dosages.

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

α1-Receptor blockade. Blockade of α1 Receptors leads to vasodilation, decreased peripheral resistance and decreased blood pressure. Autonomic side effects experienced are Postural hypotension and ejaculatory impotence.

 

Brand, L. 2021. Anti-psychotic Drugs and Lithium. Study Unit 9. [PowerPoint Presentation]. Study Unit 9, FKLG 312. Potchefstroom, NWU.