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.

1. Phenothiazine derivatives with aliphatic side chain: chlorpromazine
2. Phenothiazine with piperidine side chain: periciazine
3. Phenothiazine derivative with piperazine side chain: fluphenazine

Aliphatic and piperidine side chains have a lower potency meaning that it has less EPS side effects and a higher dosage of the drug is needed to induce the side effects as the affinity for the Dopamine receptors are not as high and thus it will bind to other receptors more likely for example to H1 receptor causing severe sedation, M receptors in the heart responsible for the cardiovascular effects, M receptors in the body accounts for the strong anti-cholinergic effects and A1 blockade responsible for postural hypotension.

Piperazine however is a high potency drug indicating a strong affinity for binding to the D receptors which is then responsible for the larger EPS side effects but less sedation, less anti-cholinergic, cardiotoxic and postural hypotension side effects

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

Mesolimbic D2 receptors are blocked in particular. Other receptors like M, alpha, H & serotonin are also blocked but to a lesser extent.

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

Atypical drugs have a stronger binding affinity for 5-HT_2A receptors more than D₂ receptors

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

The reduced risk is associated with the affinity of blockage of the D2 receptors. Lower potency drugs have a decreased chance for causing severe EPS symptoms where as high potency drugs have an increased risk. The lower potency of drugs is typically linked to having a lower affinity for binding to the D2 receptors and will possibly bind to additional receptor having anti-cholinergic effects or even some serotonergic reducing effects.

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

Haloperidol, it has a very high potency for blocking D₂ receptors primary located in the basal ganglia.

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

The autonomic systems are a system that is large manage unconsciously which regulates body functions such as heart rate, digestion, respiratory rate, urination, sexual arousal and pupillary response. Thus blocking alpha 1 receptor it influences both blood pressure (can precipitate orthostatic hypotension) and muscarinic receptor blockage influences urinary retention, blurred vision, constipation and even sexual dysfunction.

 

Brand, L. Prof.  2021.  Study Unit 9: Anti-psychotic Drugs and Lithium.  Unpublished lecture notes on efundi, FKLG 312.  Potchefstroom: NWU.  [PowerPoint presentation].