. Name an example of each of the three phenothiazine subfamilies and say how they differ from each other in terms of potency and side effects?

• Aliphatic compounds (such as Chlorpromazine)
  • Low power
  • My extra-pyramidal effects
  • Severe sedation
  • Weight gain
  • Strong anti-cholinergic effects
  • Strong alpha - lithic effects (such as postural hypotension)
  • Cardiotoxics
• Piperidine compounds (such as thioridazine)
  • Low power
  • My extra-pyramidal effects
  • Severe sedation
  • Weight gain
  • Strong anti-cholinergic effects
  • Strong alpha - lithic effects (such as postural hypotension)
  • Cardiotoxics
• Piperazine derivatives (such as flufenacin)
  • High potency
  • More extra - pyramidal effects
  • Weaker anti-cholinergic side effects
  • Weaker alpha - lithic effects
  • Less sedation
  • Less cardiovascular side effects

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

These drugs are neuroleptics drugs. The drugs block mesolimbic Dopamine2 receptors. These drugs also have anti-mimetic effects (anti-vomiting) because the Dopamine2 receptors in the CESA are blocked. Dopamine, Muscarinic, Alpha, Histamine and Serotonin receptors are blocked by antipsychotic drugs.

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

MOA for Atypical Remedies:

• Multipotent antagonists (also known as inverse agonists)
• Often higher affinity for 5 - HT2 receptors. Can also block D2.
• Some also: Strong M1 (Closapine and Olansepine), H1 (all) and alpha - 1 blocking effects (Closapine, Risperidone and Ziprasidone)
• Closapine has a pronounced D4 blocking effect, as well as for 5 - HT. But virtually no affinity for D2.
• Ziprasidone is a D2, 5 - HT2A, 5 - HT1D antagonist but a 5 - HT1A agonist.

MOA for typical drugs:

• Multipotent competitive antagonists - block DA2 receptors rather than

5 - HT2 receptors.

• Also blocks: M (Chlorpromazine and Thioridazine), alpha (Fluphenazine the least), H1 (especially Chlorpromazine and the Thioxetene) and 5 HT receptors.

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

Dopamine (D2) receptors

5. Which of the older drugs has a high incidence of extrapyramidal effects? What is the reason?

The piperazine derivatives because these drugs have a high potency and therefore tend to have more extra - pyramidal effects.

6. Due to which receptor blockade does the aliphatic group have a high incidence of autonomic side effects?

The alpha - 1 receptor blockade, because it blocks alpha receptors. These side effects include: postural hypotension, ejaculation impotence by CPZ, Droperidol and Chlorpromazine.