L14 - Drug action in the CNS - Antipsychotics Flashcards
Amine transmitters in the CNS
Noradrenaline
Dopamine
5-HT (Serotonin)
Acetylcholine
How do anti-depressant drugs exert their action?
By interfering with amine transmission.
What is the main area of action for noradrenaline?
The locus coeruleus, activity here increases with behavioural arousal, controlling wakefulness and alertness.
Where are B1 receptors located in the brain and what do they do?
Located in the cortex , the hippocampus, and the striatum.
They contribute to the long-term effects of antidepressants.
What are a2 receptors involved in?
Regulation of blood pressure, sedation and analgesia.
What are a1 receptors involved in?
Involved in motor control cognition and fear.
What is the main pathways of the action of dopamine?
1- The Nigrostriatal pathway - fine motor control
2- The Mesocortical and Mesolimbic Pathway - pleasure, reward/motivation, compulsion.
3- Tuber-hypophyseal - pituitary hormone secretion eg pituitary
What is dopamine made from?
An amino acid called tyrosine, via the action of 2 enzymes.
- Tyrosine hydroxylase (rate limiting enzyme)
- DOPA (DOPA decarboxylase)
How can we identify noradrenergic neurons?
Through the presence of B-hydroxylase.
What are the different kinds of dopamine receptor?
D1 and D5 - Gs coupled receptors, stimulate adenylyl cyclase, increase cAMP, PKA and protein phosphorylation.
D2, D3 and D4 - Gi coupled receptors, inhibit adenylyl cyclase, activate potassium channels and oppose the effect of D1 receptor activation.
Where are D2 receptors found?
In the pituitary gland and on DA neurones.
How do cocaine and amphetamines effect DA and NA?
They increase their transmission,
They stimulate secretion, displace them from vesicles and cause reuptake transporters to work in reverse.
What does increased DA signalling lead to?
increased motor activity
What are amphetamine-like drugs used to treat?
Narcolepsy and attention deficit hyperactivity disorder (ADHD)
What is schizophrenia?
a mental illness characterised by, disturbances in areas of the brain associated with thought, attention, motor behaviour and emotion.
Symptoms of Schizophrenia?
Positive - Hallucinations, paranoid delusions, thought disorders, aggression.
Negative - blunting of emotions, social withdrawal, unresponsiveness, anhedonia.
What causes schizophrenia?
It’s hereditary, a result of abnormalities that arise in early life
No single gene is responsible.
Consumption of cannabis in adolescence is one of the environmental factors.
How are schizophrenic brains structurally different?
They have larger lateral ventricles and a smaller volume of tissue in the left temporal lobe.
What drugs reduce the positive symptoms of SZ?
D2 blocking drugs (Antidopaminergics), while drugs that enhance DA signalling increase them.
What does overactivity of the mesolimbic pathway contribute to?
Positive symptoms and increased D2 activity.
What does underactivity of the mesocortical pathway contribute to?
Negative symptoms, D1 receptors are implicated.
What is the dopamine theory of Schizophrenia?
1- Amphetamines produce behaviours similar to acute SZ episodes.
2- Hallucinations are a side effect of treating Parkinson’s patients.
3- DA release in animals produces stereotypical behaviours.
4- DA antagonists and drugs that block DA storage control positive symptoms and amphetamine induced behaviours.
What are some unwanted side effects of taking antipsychotic drugs?
Parkinson’s like symptoms
Acute reversible dystonia
Increased prolactin release
Slowly developing irreversible tardive dyskinesia (involuntary movements.
What are some new drug developments for SZ?
Drugs targeting glutamate (mGluR) Receptors
