Lecture 4- Chemical Signaling And Neuromodulation Flashcards
What is neuromodulation
It modulates the activity of the neuron, alters the speed of the neurone
Neuropeptides are
Endorphins
Amino acid transmitters are responsible for
Fast transmission
What is glutamate responsible for
Excitatory causing next neurone to fire
What are GABA and Glycine responsible for
Inhibitory
Glutamate synthesised from
Glucose or glutamine
Glutamate is released by
Exocytosis (Ca+ dependent mechanism)
Too much glutamate can cause
Hyperexcitability (epilepsy)
Too little GABA can cause
Hyperexcitability (epilepsy)
What is cerebral ischemia
- Insufficient blood flow due to plaque
- Due to High glutamate
- Reversal of the Na+ K+ gradient
Receptors vary in
Pharmacology (what transmitter binds and how drugs interact)
What are agonist drugs
Produce a cellular reaction when bound to receptor
What is an antagonist drug
- Reduces or completely blocks the activity of an agonist
- No cellular effect
Receptors vary in their
- Kinetics (rate of binding)
- Selectivity (what binds)
- Conductance (rate of flux)
Glutamate receptors allow
Sodium ions influx
Excitatory
GABA receptors cause
Chloride (Cl-) influx
Inhibitory
What are the three types of glutamate receptors
- AMPA
- NMDA
- Kainate
- Named on the agonist that binds with glutamate
AMPA receptor is
- Iontropic receptor
- Leads to opening of Na+ channel
- Causes depolarisation
NMDA receptor features
- iontropic receptor
- it’s Non-competitive antagonist is PCP
- Needs glutamate and glycine to bind
- Permeable to Na+, K+ and Ca+
- Voltage gated
Which has slower kinetics, NMDA or AMPA
NMDA
AMPA and Kainate are permeable to
Na+ and K+
NMDA receptors are only activated in
An already depolarised membrane in the presence of glutamate.
This allows the magnesium blocking NMDA to be dispelled
What are NMDA receptors blocked by
- Magnesium
- PCP (the drug)
Certain antipsychotic drugs enhance current flow through
NMDA channels
Glutamate excitotoxicity caused by
Excessive Ca+ influx which activate things that damage the cell
Occurs after stroke
NMDA receptors associated with what illness
Schizophrenia
Too much GABA can cause
Sedation, coma
GHB (date rape drug) causes
Increases amount of available GABA
Alcohol acts at what receptor
GABA a
GABAa receptor
- Iontropic
- Ligand gated Cl- channel
- Fast IPSP
- Inhibitory
- Multiple binding sites
GABAb receptors
- Metabotropic receptor
- G protein coupled receptor
- Indirectly coupled to K+ (opens) or Ca2+ (closes) channels
- Slow IPSPs
- Inhibitory
GABAa increases
Chloride permeability and hypolarises the neuron
What’s GABA agonist and antagonist
Agonist- muscimol (a mushroom)
Antagonist- bicuculine, picrotoxin
Drugs increasing GABA activity reduce anxiety
Agonist- Alcohol, barbiturates
Indirect antagonist- Benzodiazepines
Drugs decreasing GABA activity increase anxiety
Antagonist- Flumazenil (reverses effects of benzodiazepines)
Patients with panic disorders have less
Benzodiazepine binding dites
If you have GABA and the barbiturate it results in
Bigger hyperpolerisation
When be benzodiazepines are applied on their own it results in
- No effect
- GABA and benzodiazepines results in an effect
Problems with barbiturates
- General depression of neuronal activity, can result in not breathing
- Poor therapeutic ratio (small difference between dose and overdose)
- Long term treatment leads to dependence
Why are benzodiazepines better for calming anxieties
- Indirect antagonist on its own
- Fast acting
- Large therapeutic window
Disadvantages of benzodiazepines
- May cause dependence
- Effects potentiated by alcohol
Dopamine neurons are where
- Cell bodies in the midbrain
- Project into the forebrain
3 key dopamine pathways
- Role in movement
- Role in reinforcement
- Role in working memory and planning
Damage to movement system (nigrostiatal system)
- Parkinson’s disease
- Huntington’s disease
Damage to reward system (mesolimbic system)
Addiction to drugs
Damage to working memory system (mesocortical system)
Schizophrenia
Dopamine synthesis
- Tyrosine to
- L-Dopa to
- Dopamine
What drugs affect dopamine synthesis
- Reserpine, impairs storage of dopamine
- L-DOPA, precursor of dopamine, used to treatment for Parkinson’s disease, increases dopamine
AMPT inactivates
TH
Dopamine release causes
- Depolarisation of presynaptic membrane
- Influx of Ca2+ through voltage gated Ca2+ channels
After release, cytoplasm dopamine is
Reloaded back into vesicles and enzymatically degraded
Drugs that affect dopamine release and reuptake
- Cocaine, amphetamine and methylphenidate
- Selegiline
- Entacapone
What do psychostimulants (cocaine) do to dopamine release
- Block reuptake of monamines
- Extended action of dopamine on postsynaptic neuron
What can drugs that affect dopamine release and reuptake also do
- Have antidepressant activity
- Can treat Parkinson’s
What does the noradrenergic system do
- Role in arousal and attention
- Role in anxiety, heroin withdrawal, depression
Where does the serotonergic system project
Throughout the cerebral cortex
What does the serotonergic system function in
- Mood
- Sleep
- Pain
- Appetite
Process of serotonin synthesis
- Tryptophan
- 5-hydroxytryptophan
- Serotonin
More tryptophan might help
Improve your mood
Serotonin released through
Ca2+ dependent mechanism
What degrades dopamine and serotonin
MAOs
Drugs that affect serotonin
- Fluoxetine (Prozac)
- Fenfluramine
- MDMA
What does fluoxetine do
Blocks reuptake of serotonin
Antidepressant
What does fenfluramine do
Causes release of serotonin and inhibits it’s reuptake.
Appetite suppressant
What does MDMA do
- Causes noradrenaline and serotonin transporters to run backwards.
- Neurotransmitters into synapse
What is acetylcholine synthesised from
Choline
What can acetylcholinesterase inhibitors do
- Treat Alzheimer’s
- Myasthenia gravis
- Autoimmune disorders
Drugs that affect vesicle docking and release
- Botox
- Botulinum
- tetanus toxins
Tetanus prevents
Glycine release
Tetanus toxin causes
Disinhibits the cholinergic neurons so they continually fire resulting in permanent muscle contraction
