Lecture 12 - Drug action in the CNS - antipsychotics Flashcards
What do amine transmitters in the CNS do?
Found in small populations in specific brain regions
Emotions, cognition & awareness
- Noradrenaline
- Dopamine
- 5-hydroxtryptamine
- Acetylcholine
- Localised to small populations of neurons with cell bodies in the brain stem & basal forebrain
- associated with ‘high level behaviours’ e.g. emotions, cognition and awareness
- many anti-psychotics, known as known ‘neuroleptics’, used in the treatment of schizophrenia
- anti-depressant drugs exert their actions interfering the amine transmission.
What are 3 functional aspects of dopamine?
- Nigrostriatal pathway - fine motor control
- Mesocortical and mesolimbic pathways - behavioural effects, stereotypical, perseverance, pleasure-euphoria-rewards (motivation), compulsion
- Tuberohypophyseal pathway - pituitary hormone secretion - e.g. Prolactin
Describe features of noradrenaline
- A1 receptors widely distributed, involved in motor control, cognition, fear
- A2 involved in regulation of blood pressure, sedation and analgesia
- B1 in cortex, striatum and hippocampus contribute to long term effects of antidepressants
- LC (locus coeruleus) neuronal activity is increased with behavioural arousal, controls wakefulness and alertness, control of mood (deficiency linked to depression)
Describe the process of the creation of adrenaline
Tyrosine (tyrosine hydroxylase) –> DOPA (DOPA decarboxylase) –> Dopamine (dopamine B-hydroxylase) –> noradrenaline (Phenylethanolamine N-methyltransferase) –> Adrenaline
What is dopamine a precursor for?
- Dopamine is precursor to noradrenaline.
- Made in cytosol, then transporters found on vesicle membrane is involved in dopamine transportation.
- Enzymes found inside neurons
What type of receptors does dopamine bind to?
only binds to G-protein receptors
How can measurements of dopamine metabolic products can used to monitor dopamine release in patients
Breakdown products found in the urine, so this can be measured
What are the 2 families of dopamine receptors?
D1 & D5 - Gs coupled receptors, stimulate adenylyl cyclase. Increase cAMP, PKA and protein phosphorylation
D2, D3 & D4 - Gi coupled receptors, inhibit adenylyl cyclase. Activate potassium channels, inhibit VGCC (voltage-gated calcium channels). Oppose effects of D1 receptor activation.
Where are DA (dopamine) receptors in brain?
- dopamine receptors in brain in distinct but overlapping areas
- D2 receptors found in pituitary and on dopamine neurons (inhibitory autoreceptors)
What is associated with unwanted side effects?
Lack of selectivity with dopamine receptor agonists and antagonists
- drugs will increase dopamine release will affect all pathways
What type of transmission does amphetamines and cocaine increase?
- dopamine
- noradrenaline
What do amphetamines do?
Amphetamines stimulate secretion of dopamine and noradrenaline, displace dopamine & noradrenaline, cause re-uptake transporters to work in reverse
What does cocaine do?
Cocaine inhibits dopamine
What does increase dopamine signalling lead to?
increased motor activity
What are amphetamine-like drugs used to treat?
narcolepsy (stimulate wakefulness) and attention deficit hyperactivity disorder (ADHD) - increase concentration
What occurs in animals in the presence of cocaine?
animals’ stereotypical behaviours activation of reward pathways & feelings of euphoria (in the limbic system)
What are symptoms of schizophrenia?
- characterized by disturbances in the area of the brain associated with thought, perception, attention, motor behaviour & emotion
What is the prevalence rate for schizophrenia?
approximately 1.1% of the population over the age of 18 –> at any one time as many as 51 million people worldwide suffer from schizophrenia
- over 250,000 diagnosed cases in the UK
Describe the positive symptoms of schizophrenia
- hallucinations (voices)
- delusions (paranoid)
- thought disorders (irrational/wild delusions of grandeur. garbled sentences)
- Defects in selective attention
- BIzarre behaviour
- Aggression
- Stereotyped movements
- Catatonia (affects movement)
What are the negative symptoms of schizophrenia?
- blunting of emotions
- withdrawal from social contacts
- flattening of emotional responses
- anhedonia (reduced motivation to feel pleasure)
- reluctance to perform everyday tasks
What may happen to ventricles of people with schizophrenia?
Enlarged ventricles
What accompanies schizophrenia?
- cognitive defects (attention, memory)
- anxiety
- depression
- self-punishment
Describe the suicide figures associated with schizophrenia
50% cases - 10% successful
What are the causes of schizophrenia?
environmental &
- found to be hereditary and a result of abnormalities which arise early in life and disrupt the normal development of the brain
- no single gene is responsible
- consumption of cannabis in adolescence is one of the environmental factors
- increase in D2 agonist = schizophrenia (increase in positive symptoms) - antagonist = opposite
