Antipsychotic-induced parkinsonism
Antipsychotics (drugs used for schizophrenia) can cause parkinsonism, with slowed movements, tremor and rigidity, by blocking D2 receptors (a type of dopamine receptor) in the nigrostriatal pathway, which controls movement.
Remember
Blocking D2 receptors in the nigrostriatal pathway, the dopamine pathway for movement, causes drug-induced parkinsonism, and typical (first-generation) antipsychotics are more likely to cause it than atypical (second-generation) drugs.
Memory aid
atypical drugs knock on the D2 receptor and leave quickly; typical drugs stay
Atypical drugs knock and leave quickly, whereas typical drugs stay on the D2 receptor, which is why typical drugs are more likely to cause parkinsonism.
Antipsychotics are the mainstay of treatment for schizophrenia. They work by blocking D2 receptors, a type of dopamine receptor, in the dopamine pathways of the brain.
Typical (first-generation) antipsychotics were the first to be developed. They block D2 receptors strongly, which makes them very effective, but they give severe side effects once dopamine pathways other than the target pathway for hallucinations and delusions are blocked too.
The pathway that carries dopamine for movement control is the nigrostriatal pathway. Dopamine travels along it from the substantia nigra, an area in the midbrain, to the striatum, a deep part of the brain that helps control movement. Dopamine there normally supports smooth movement, so blocking its D2 receptors causes drug-induced parkinsonism: slowed movements (bradykinesia), tremor and muscle rigidity. These are extrapyramidal side effects, meaning movement effects arising outside the main motor pathways.
Typical drugs block D2 receptors with high affinity, meaning they bind to them strongly, and they also stay on the receptor longer. Atypical (second-generation) antipsychotics also act on D2 receptors but with a lower affinity, so they come off the receptor more quickly (they dissociate faster). That leaves more normal dopamine signalling in the nigrostriatal pathway, so they cause less parkinsonism. Both groups can cause these effects, but the first-generation drugs are more likely to.
Key facts
- Pathway blocked
- the nigrostriatal pathway carries dopamine used for movement control, so blocking it causes parkinsonism.
- Features
- slowed movements (bradykinesia), tremor and muscle rigidity.
- Typical drugs
- in several dopamine pathways, first-generation antipsychotics block D2 receptors with high affinity.
- Atypical drugs
- second-generation antipsychotics have a lower affinity for D2 receptors and dissociate faster, so parkinsonism is less likely.
- Extrapyramidal effects
- side effects on movement that arise outside the main motor pathways.
- Prolactin
- blocking the tuberoinfundibular pathway (the dopamine pathway that helps regulate the release of prolactin, a hormone) raises prolactin and does not cause a movement disorder.
Exam traps
- Blocking the tuberoinfundibular pathway, the dopamine pathway that helps regulate the release of prolactin (a hormone), raises prolactin. That is a hormonal side effect and not a movement disorder.
- Higher affinity for D2 receptors does not explain why second-generation drugs cause fewer Parkinsonian side effects, because high affinity is the property of first-generation drugs and is why they cause more movement side effects.
- Irreversible binding to D2 receptors does not explain why second-generation drugs cause fewer Parkinsonian side effects, because it would keep the nigrostriatal pathway blocked and be expected to increase movement side effects.
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