Lecture 7 Flashcards
What are anti-psychotics?
drugs that target amine neurotransmitters
What is schizophrenia?
symptoms are characterised by mood, motor behaviour, perception, thought
1.1%prevalance- 250,000 in the UK
Unstable moods and emotion with unproductive repetitive behaviour
What are some causes of schizophrenic symptoms?
Meth and cocaine
arise due to imbalance of dopamine signalling
What are the symptoms of positive schiz?
More prevalent in the young aggression catatonia hallucinations, delusions repetitive and predictable behaviour defect in selective attention
What are the symptoms of negative schiz?
more prevalent in the elderly reluctant to perform everyday tasks negative state of mind blunting of emotions flattening of emotional responses withdrawal from social contacts anhedonia
What are cognitive deficits?
attention, memory and learning
What are the causes of schiz?
Is hereditary as a result of failure to develop NS- can arise early or later in life
Genome wide studies show that there is no single channel cause but there are structural differences= larger lateral ventricles and smaller left temporal lobe
What drugs give rise to positive schiz symptoms?
Drugs that enhance dopamine signalling e.g. meta amphetamines
Glutamate antagonist and 5HT agonist (LSD)
What is the function of D1 and D5 receptors?
Are Gs coupled receptors that activate adenylate cyclase for increase in neurotransmission
What is the function of D2,3 and 4 ?
Are Gi coupled receptors that inactivate adenylate cyclase to inhibit neurotransmission on inhibitory neurons
How does DOPA effect mental health?
Is implicated in cognitive defects, learning, attention, movement
Is the primary NT affected by illegal drugs e.g. cocaine, amphetamines, opioids
Associated with primary schiz symptoms
What parts of the brain are associated with schiz dopa activity?
1) Nigrostriatal pathway= motor control (lost in Parkinson’s)
2) Mesocortical and mesolimbic= euphoria, perseverance, pleasure,
3) Tubularhypophyseal pathway= pituitary gland- involved in the release of hormones e.g. prolactin
4) Medullary chemoreceptor trigger zone= nausea and vomiting
Describe the synthesis of dopamine
tyrosine (tyrosine hydroxylase= DOPA
DOPA (DOPA decarboxylase)= dopamine
dopamine (Dopamine B hydroxylase)= noradrenaline
noradrenaline (PNMT)= adrenaline
Why is it difficult to find drugs that specify for dopamine inhibitors?
Because dopamine is a precursor for other amine neurotransmitters therefore their ligand binding sites on the Rs are similar due to their similar structures
How do D2 receptors work and how is DA handled?
They feedback to inhibit their own neurotransmission
They are taken up and degraded by COMT and MAO to produce DOPAC and HVA
What’s a treatment of Parkinson’s and how does it affect schiz?
Administration of L-DOPA to increase dopamine synthesis
Increases schiz symptoms of hallucinations etc
How do illegal drugs work e.g. amphetamines and cocaine and what are their symptoms?
Cause schizophrenic like symptoms as they increase the duration of catecholamines at the nerve terminal by inhibiting MAOs resulting in the pumps working in reverse (accumulate in the neuron and will travel back out). They increase euphoria, sympathetic systems, reward, increase in motor systems. Result in neurotoxicity as the metabolism of dopamine creates a reactive intermediate which results in neuronal cell death.
What are amphetamines used to treat?
Narcolepsy and ADHD
What are NMDA R antagonists cause?
They cause positive and negative schiz symptoms which proves that glutamate is involved e.g. ketamine and phencyclidine
What is used to treat schizophrenia?
D2 receptor antagonists to decrease positive symptoms of schiz associated with the mesolimbic pathway
What are the side effects of halperidal and chlorpromazine?
They are antipsychotic
motor disturbances
prolactin release
activation of nigral striatal pathway
What is risperidone?
Anti-psychotic
5HT 2a, D1 and D2, alpha 1 and H1
What is clozapine?
antipsychotic
same as risperidone but also mACHR
Sulpiride
More specific to D2= less side effects
anti-psychotics
Phenothiazine e.g. chlorpromazine
anti-psychotic
preference to D2
side effects= acute dystonia (reversible) and tardive dyskinesia (irreversible)
