Drugs & Synaptic Transmission Flashcards
Where is Nor Adrenaline stored in the body?
In vesicles
Name 3 examples of cholinesterase inhibitors
Short acting - Edrophonium
Medium term - Neostigmine or Physotigmine
Irreversible - Parathion, ecothiophate or dyflos
What are the 2 ways reuptake of NA occurs?
Uptake 1 - via (NET) neuronal transporter of
unmetabolised NA - high affinity
Uptake 2 - via (ENT) extraneuronal monoamine
transporter - low affinity
What is the effect of cholinesterase inhibitors?
Raise Ach levels as Ach not degraded
Which toxins affect SNARE proteins on cholinergic nerves?
Tetanus virus Botulinim toxin (peptidase)
How is Nor Adrenaline produced from its precursor tyrosine?
- Tyrosine -> DOPA (dihydroxyphenylalanine) via Tyrosine
Hydroxylase - DOPA -> Dopamine via DOPA Decarboxylase
- Dopamine -> Nor Adrenaline via Dopamine β hydrolase
(4.) NA -> Adrenaline via Phenylethanamide N-
methyltransferase
What is the effect of toxins on the cholinergic synapse?
Inhibit vesicular fusion process
Where is adrenaline stored?
In β glands in the liver
Which drugs are used to stimulate adrenergic synapses?
- Amphetamine
- Tyramine
- Ephedrine
Taken up instead of NA which can’t compete
How is the cholinergic synapse regulated?
Via Na+ channel blockers (e.g. lignocaine)
Via neuronal Ca2+ channel blockers (e.g. conotoxin analogue zicnotide)
How is adrenergic synapse activity regulated?
By clinically used and research based drugs
What is the function of the drug Hemicholinium ?
Inhibits the uptake of precursor Choline
How do vesicles release their contents?
Using SNARE proteins to fuse with the membrane to release their contents
What is the precursosr of Nor adrenaline?
Tyrosine
How do MOA inhibitors work to regulate adrenergic synapses?
e.g. Tranylcypromine Isocarboxazid
blocks MOA enzymes
Tyramine taken up - displacing NA
NA spills out uncontrollably of vesicles
What is the role of the drug Vesamicol?
Prevents choline storage in vesicles by displacing it
What is the effect of toxins on SNARE proteins?
Toxins eat away at SNARE proteins on cholinergic nerves
What are the functions of the 2 parts of the botulinim toxin?
1 - binds to choline transporter enables 2nd part
2 - Degradative part to get into cell
Which part of the autonomic system do adrenergic synapses work with?
Sympathetic nervous system
Name clinical drugs used to regulate adrenergic synapses
- Desipramine
- Imipramine
- Cocaine
What induces the production of the precursor choline?
Uptake of Choline driven by the depolarisation of the cell by Na+
Outline the events at an adrenergic synapse leading to a response
- Nor Adrenaline synthesised
- Storage of NA in vesicles
- Depolaristaion in nerve terminal due to influx of Na+
- Causes Ca2+ channels to open
- [Ca2+] increases
- Ca2+ binds to synpatotagmin stabilising snare pin
- Creates kink in membrane causing vesicle pore ot open
- Release of NA neurotransmitter across synapse to
interact with receptors on postsynaptic membrane - Re uptake of unmetabolised NA by Neuronal
transporter
How does Botulinim toxin degrade SNARE proteins?
By heating to >85℃ for >5mins
How is Ach inactivated at a cholinergic synapse?
Ach degraded into Choline + Acetate by cholinesterase enzyme
- inactivates receptor
- choline can be used again via re uptake
Outline how the SNARE proteins cause vesicular fusion
- VAMP interacts with Syntaxin-1 or SNAP25 when
synaptotagmin binds to Ca2+ - tSNARE-vSNARE complex forms –> snare pin
- Snare pin pulled closer to membrane
- Ca2+ bound synaptotagmin stabilises snare pin
- Creates kink in membrane enabling vesicle pore to
open - Vesicular contents released
What is the effect of neurotoxins?
Inhibit neurotransmitter release from vesicles
Outline the events that take place at a cholinergic synapse
- Precursor Choline synthesised
- Choline –> AcetylCholine via choline acetyltransferase
- Ach stored in vesicles
- Voltage gated Na+ channels open creating influx of
Na+ - Causes Ca2+ channels to open
- Ca2+ binds to synpatotagmin, stabilising snare pin
- Creates kink in membrane causing veiscle pore to open
- Release of Ach across synapse
- Ach Inactivated after interaction with postsynaptic
membrane
What is the effect of drugs used clinically to regulate adrenergic synpases?
Block uptake mechanism of NA back into nerves
NA receptors are therefore always activated
=> [NA] high
What are the 2 types of SNARE proteins?
VSNAREs - in vesicles (synaptobrevin & VAMP)
TSNAREs - on membrane (syntaxin-1 & SNAP25)
Name the drugs used in research to regulate Adrenergic synapse activity
Reserpine - stops NA uptake into vesicles
Guanethidine - displaces NA in vesicles
Which part of the autonomic nervous system do cholinergic synapses operate on?
Parasympathetic nervous system
