Neurotransmitters Flashcards
Glutamate
major excitatory amino acid small molecule neurotransmitter in the CNS
GABA
- main inhibitory NT in brain
- synthesised from Glutamate by glutamic acid decarboxylase
- loaded into synaptic vesicles by VIAAT
- cleared by GATs - Na+ dependent co-transporters
GABA receptors
- GABAa ionotropic (chloride channels)
- GABAb metabotropic (inactivated K+ channels or inhibit Ca2+ channels)
GABAa receptor pharmacology
- agonists widely used sedatives, anxiolytics, anti-convulsants, anaesthetics
- barbiturates e.g. pentobarbittal activate
- benzodiazepines enhance
- inhibitors used experimentally as convulsants (epilepsy models)
GABA modulation - clinical application
- GABAa receptor antagonists e.g. flumazenil used clinically for benzodiazepine overdose
- GABAb receptor agonists e.g. baclofen used for spasticity
- GABA reuptake inhibitors e.g. tiagabine/gabitril used for anxiety and epilepsy
- GABA analogues e.g. gabapentin used for seizures and neuropathic pain
Why is GABA excitatory in early development/immature nervous system
- immature neurons express high levels of NKCC1 which transports chloride into cells
- high intracellular concentration of ch
Glycine
- main inhibitory neurotransmitter in the spinal cord and brainstem
- synthesised from ser by serine hydroxylmethyltransferase
- loaded into synaptic vesicles by VIAAT
- cleared by specific GlyT (mutations give hyperglycaemia, lethargy, seizures, MR)
Glycine receptors
- ionotropic (CL- channels)
- 5 subunits, each 4 TM
- clustered
- specifically inhibited by strychnine - induces seizures
Purines
- ATP excitatory NT in CNS and PNS
- ATP rapidly catabolised to adenosine
- ionotropic receptors for ATP (P2X), metabotropic receptors for ATP (PY2) and adenosine (P1)
In what are purinergic receptors modulated for therapeutic benefit
for signalling roles outside the CNS - e.g. P2Y12 inhibitors anti-platelet agents
biogenic amines
- Catecholamines (dopamine, norepineprhine, noradenaline
- imidazoleamine - histamine
- indoleamine - serotonin
What is the pathway by which catecholamines are synthesised
L-TYROSINE converted into L-DOPA converted into DOPAMINE converted into NORADRENALINE and ADRENALINE
What are the commonalities of catecholamine synthesis
- loaded into vesicles by VMAT
- catabolised by MAO and COMT
- targets of recreational drugs
Dopamine functions and disease
- REDUCED in parkinson’s
- motivation, reward and enforcement (drug addiction)
- cognition and emotion (schizophrenia dopamine theory - antipsychotics target D2 dopamine receptors)
Dopaminergic projections
- From substantia nigra via nigrstriatal pathway to striatum
- From VTA via mesostriatal pathway from midbrain to stratum
- mesocortical pathway (midbrain out to cortex)
