lecture 17: drug types in neuropharmacology Flashcards
(26 cards)
what is a drug
drugs cause physiological effects by making chemical changes at biological targets (proteins, DNA, cell membranes)
explain how drugs cause effects in the body
- drugs cause effects by forming intermolecular interactions with receptors, transporters, and enzymes that change their 3D structure
- this change in structure changes their activity
- the change in activity changes the intracellular signalling
- the change in intracellular signalling leads to a change in physiological response
–> this can include changes in heart rate, reaction time, sensation of pain
biological targets of drugs in neuroscience (with examples)
- receptors (caffeine)
- enzymes (acetylcholinesterase inhibitors)
- transporters (methylphenidate)
what is the exception to biological targets of drugs in neuroscience
- alcohol can have some membrane activity, most of its effects are due to its activity at the GABA receptor
how do agonists target receptors
- drugs interact with receptors by a lock and key mechanism
- drugs (key) trigger the receptor (lock) to behave differently
- agonist drugs can increase receptor activity by causing a change in protein shape when they bind (an increase in receptor activity results in more signals sent)
how do agonists work
- agonists work by increasing activity of a receptor
- drug agonists typically bind in the same area as the endogenous (natural) agonist
eg: morphine and nicotine
–> they can fit better than your body’s natural agonist
= prolonged stimulation of the receptor = more cell signalling
affinity
a drugs ability to bind a receptor
what is the purpose of taking drugs
–> to get a physiological response
- decrease pain
- increase muscle contraction
- improve mood
- decrease blood pressure
partial vs full agonist
- a full agonist can cause a maximum physiological response (maximum efficacy)
–> adrenaline can increase heart rate - 200BPM, the physiological maximum - a partial agonist causes a response below the maximum response
–> xamoterol is a partial agonist that increases heart rate to -110 BPM, below the physiological maximum
–> even if you use high amounts of partial agonists, still won’t get same affect of full agonist
physiological responses of adrenaline (full agonist)
- adrenaline is a hormone released during the “fight or flight response” that increases heart rate, blood pressure, and lung capacity
- adrenaline binds to G-protein coupled receptors in the heart and blood vessels
how do we measure biological response?
–> sometimes its easy
- heart rate, blood pressure
–> sometimes its hard
- depression, anxiety, psychosis
–> effect size is a common way to determine efficacy in neuropharmacology
- how good is a drug at treating depression?
- effect size of 0.5 means 29% improvement
- effect size of 1 means 48% improvement
- effect size of 1.5 means 64% improvement
how do antagonists target receptors
–> antagonists work by decreasing activity of a receptor in the presence of an agonist
- eg: caffeine, clozapine, hyoscine
- they can bind a receptor, but don’t cause any effect = this blocks the natural agonist from from binding, so no signals are given
–> antagonists have no effect by themselves, they do not activate receptors
- antagonists have no efficacy
how does caffeine work as an antagonist
- caffeine is an adenosine receptor antagonist
- adenosine is the endogenous agonist for adenosine receptors
- adenosine receptors type 1 (A1) are Gi-coupled GPCRs
–> decreases intracellular cAMP which can decrease neuron firing
where does adenosine come from?
- adenosine triphosphate (ATP) is the cellular unit of energy
- As ATP is used for energy it is converted to adenosine
- throughout the day, the buildup of adenosine activates adenosine receptors (A1)
–> activation of A1 receptors decreases neuron firing and causes us to sleep
caffeine mechanism of action
- caffeine binds to the A1R preventing adenosine from binding = prevents A1R activation
- preventing A1R activation increases cAMP and prevents hyperpolarisation
= neurons are more likely to fire (depolarise )
= caffeine decreases inhibitory effect of adenosine increasing wakefulness
physiological effects of caffeine
- in a well rested state caffeine causes improvements in some aspects of cognition
-in a sleep deprived state caffeine causes improvements in aspects of cognition such as
1. information processing
2. reaction time
3. driving test scores
caffeine effects under rested state
- reaction time did not significantly improve
- executive control significantly improved by an effect size of 1.41
caffeine under sleep deprived state
- reaction time significantly improved by an effect size of 1.11
- executive control significantly improved by an effect size of 1.95
- driving test scores improved by an effect size of 1.63
caffeine and adenosine receptors in rested state
- low adenosine levels
- low A1 activity
- caffeine changes A1 activity from low to very low
caffeine and adenosine receptors in sleep-deprived state
- high adenosine levels
- high A1 activity
- caffeine changes A1 activity from high to low
enzyme inhibition
drugs that target enzymes typically bind to them and stop them from working
inhibitors = drugs that do this
what does enzyme inhibition lead to
- a buildup of endogenous agonists
- this leads to more receptor activation
classes of drugs that inhibit enzymes
- monoamine oxidase inhibitors can be used to treat parkinsons disease and depression
- protease inhibitors are common antiviral drugs
- drugs that inhibit enzymes involved in cell replication are common anti-cancer drugs
–> many drugs are inhibitors of liver enzymes as an unwanted side effect unrelated to their primary mechanism of action - fluoxetine and bupropion inhibit CYP3A4
mechanism for drugs targeting transporters (inhibitors)
–>transporters are proteins that transport molecules from one side of a cell membrane to another
- this can mean molecules will move from the cytoplasm outside the cell, or outside the cell into the cytoplasm
- an inhibitor of a transporter will block the transport of molecules
–> many drugs that treat psychological disorders target transporters
- selective serotonin reuptake inhibitors (SSRIs) for depression = fluoxetine
- norepinephrine and dopamine reuptake inhibitors (NDRIs) for ADHD = methylphenidate (ritalin)
