• 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.

• Aliphatic sidechain: Chlorpromazine
• Piperidine sidechain: Periciazine
• 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?
  • 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: block 5-HT_2A receptors more than D₂. 
  • Typical drugs: block DA 2 receptors in the mesolimbic

• Which of the receptors blocked by the older drugs reduce the risk of extrapyramidal side effects?
  • Benzamides such as sulpiride and amisulpride block D₂ and D₃ receptors. The risk of extra pyramidal side effects is reduced due to the limbic localisation of the D₃ receptors.

• 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. Piperazine drugs such as Fluphenazine, perphenazine, trifluoperazine, prochlorperazine

• Because of which receptor(s) blockade do the aliphatic group of drugs have a high incidence of autonomic side effects?
  • Autonomic side effects occur as a result of Muscarinic and α1 blockade effects.

Brand, L. 2021. Antipsychotic drugs and lithium salts. SU. 9 [PowerPoint Presentation]. Unpublished Lecture Notes on eFundi, FKLG 312. Potchefstroom, NWU.

Katzung, B.G. 2018. Basic and Clinical Pharmacology. 14^th ed. United States of America: McGraw-Hill Education