Lecture 8 Flashcards
What is an example of a catecholamine?
- noradrenaline - dopamine
What is an example of a tryptamine?
Serotonin
What does noradrenaline regulate?
- arousal/wakefulness/alertness (forebrain) - mood (amydgala/hippocampus) - pain control (spinal cord) - BP/autonomic function (hypothalamus)
What does dopamine regulate?
- motor control (nigrostriatal system) - behaviour/mood (mesolimbic/mesocortical systems) - endocrine control (tuberohypophyseal system)
What are the dopamine receptors which are D1-like?
- D1 - D5
Which G-protein does D1-like receptors bind to?
G𝛼s
What are the second messengers of D1-like receptors?
(Increased activity of) cAMP and PKA
What are the dopamine receptors which are D2-like?
- D3 - D4
Which G-protein does D2-like receptors bind to?
G𝛼i
What are the second messengers of D2-like receptors?
- (reduced activity of) cAMP and PKA - Gβ𝛾 decreases voltage-gated Ca2+ channels - Gβ𝛾 opens K+ channels
What are the physiological responses of dopamine activation?
increase BP + heart rate
What does serotonin regulate?
- sleep, wakefulness and mood - feeding behaviour - control of sensory transmission
What is the physiological response of 5-HT receptor activation?
- feeding - mood/behaviour (antidepressants) - sleep/wakefulness - control of sensory pathways (hallucinations) - pain (migraine) - body temperature
What is the physiological response of 5-HT3 activation?
Vomiting (chemotherapy)
What G protein does 5-HT1 bind to?
G𝛼i
What are the typical second messengers of G𝛼i activation?
- (reduced activity of) cAMP and PKA - Gβ𝛾 inhibits voltage-gated Ca2+ channels - Gβ𝛾 opens K+ channels
What G protein does 5-HT2 bind to?
G𝛼q
What are the typical second messengers of G𝛼q?
- Protein Kinase C - Ca2+
What G protein does 5-HT4, 5, 6 and 7 bind to?
G𝛼s
What are the typical second messengers of G𝛼s?
(Increased activity of) cAMP and PKA
What is 5-HT3 receptor bound to and what are the second messengers?
- ion channel - Na+ - Ca2+
Where do psychoactive drugs target monoamine uptake?
- plasma membrane - synaptic vesicle
What are the effects of psychoactive drugs on monoamine uptake?
Monoamine accumulation in the cleft
What transporter does cocaine inhbit?
DAT (dopamine)
What transporter does MDMA target?
- SERT (serotonin) - taken up into the presynaptic terminal - VMAT
What transporter does amphetamine target?
- NET (noradrenaline) - taken up into presynaptic terminal - VMAT
What enzyme does amphetamine inhibit?
Monoamine oxidase
What are the main effects of amphetamines?
- increased motor activity - euphoria and excitement - insomnia - anorexia
What is a mental effect of prolonged amphetamine use?
Amphetamine psychosis which resembles symptoms of schizophrenia
What are the clinical uses of amphetamines?
- ADHD (adderall, ritalin) - narcolepsy (adderall, ritalin) - obesity (methedrine)
What are the main effects of cocaine?
- increased motor activity - euphoria - increased peripheral sympathetic activity (increased BP, HR)
What are the main effects of modafinil?
- increased wakefulness and vigilance
Where does modafinil bind to?
Low affinity to DAT and NET
What are examples of cognitive enhancers?
- caffeine - modafinil - methyphenidate - ampakines
What are cognitive enhancers used for?
- reduce mental fatigue - maintain attention and concentration - increase motivation - alter (enhance) memory processing - normalise behaviour e.g. schizophrenia, autism
How do ampakines work?
- enhance glutamate AMPA activation - promote release of brain-derived neurotrophic factor (BDNF)
What is the monoamine theory of depression?
- drugs that enhance MA levels improve mood and symptoms of depression - vice versa for drugs lowering MA levels e.g. reserpine
List brain areas associated with depression
- amygdala - basal forebrain - cerebellum - hypothalamus - nucleus accumbens - prefrontal cortex - striatum - thalamus
What are the types of antidepressant drugs?
- monoamine oxidase inhibitors - monoamine uptake inhibitors
What are the types of MA uptake inhibitors called?
- tricyclics - selective - dual action
What do monamine oxidase inhibitors target?
- monoamine oxidase (prevents MA breakdown) - e.g. phenelzine
Do tricyclic antidepressents target NET or SERT?
- both - e.g. imipramine
What are examples of selective monoamine uptake inhibitors?
- citalopram - fluoxetine (Prozac) - reboxetine
How do dual action monoamine uptake inhibitors work?
- target both NET and SERT (SNRI) - e.g. duloxetine
What are the areas associated with dopamine in schizophrenia?
- mesolimbic pathway (positive symptoms) - mesocortical symptoms (negative and cognitive symptoms) - nigrostriatal system (motor symptoms from drug therapy) - tuberohypophyseal (hormonal disturbance from drug therapy)
What are the positive symptoms of schizophrenia?
- delusions/paranoia - hallucinations - disordered thoughts - abnormal behaviour e.g. stereotyped movements - catatonia/immobility
What are the negative symptoms of schizophrenia?
- social withdrawal - flattening of emotion - anhedonia - apathy
What are examples of first-generation antipsychotic?
- chlorpromazine - haloperidol
Where do first-generation antipsychotics target?
D1 and D2 receptors (but has other targets)
What are examples of second-generation antipsychotics?
- clozapine - risperidone
Where do second-generation antipsychotics target?
Some D1 activity but most at D2
What are some side effects of antipsychotic drugs?
- motor effects - increased prolactin secretion (gynecosmastia and galactorrhea) - weight gain - sedation/drowsiness
What are the motor effects of antipsychotic drugs?
- extrapyramidal effects - D2 receptor antagonism (nigrostriatal pathway) - involuntary movements/spasms/tremor (Parkinson’s symptoms) - acute dystonias (reversible) - tardive dyskinesia (irreversible)
What are the areas associated with dopamine in Parkison’s?
- tuberohypophyseal pathway - mesocortical pathway - mesolimbic pathway - nigrostriatal pathway - substantia nigra (loss of neurones)
What are the symptoms of Parkinson’s?
- suppression of voluntary movements (bradykinesia) - tremor at rest - increased resistance in passive limb movement - variable degree of cognitive impairment
What are the two therapies used to treat Parkinson’s disease?
- drug therapy - deep-brain stimulation
What is deep brain stimulation?
Parkinson’s disease treatment where an electrical device is planted in the brain to stimulate structures and decreases PD symptoms.
What are examples of drugs that act in the periphery to treat Parkinson’s?
- carbidopa - benserazide - entacapone - tolcapone
How do drugs in the periphery help treat Parkinson’s?
Prevent conversion of levodopa to - dopamine (carbidopa, benserazide) - 3-MethylDopa (entacapone, tolcapone)
What are examples of drugs that act in the brain to treat Parkinson’s?
- selegillline - rasagiline - tolcapone
How do drugs in the brain help treat Parkinson’s?
Prevent conversion of dopamine to - DOPAC (selegiline, rasagiline)
What are examples of agonists at D1 and D2 receptors?
- pramipexole - ropinirole - rotigotine - bromocriptine - apomorphine
