Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
6 Cards in this Set
- Front
- Back
|
GABA (Gamma-aminobutyric acid) - Metabolism and Receptors |
What? Inhibitory NT in brain METABOLISM 1. Synth from L-glutamate by glutamic acid decarboxylase 2. Synaptic removal by GAT -> GABA transporter 3. Catabolism of GABA->succinate by GABA-T RECEPTORS GABAa - ligand gated ion-channel, pentameric 4TM subunits, GABAa-rho=5 subunit ligand-gated ion channel GABAb - heterodimer of two 7TM subunits -GABAb1 binds only GABA, GABAb2 binds +ve allosteric modulators - decrease Ca fluxes in presynaptic membrane, increase K fluxes in post synaptic membrane |
|
|
GABA Cellular Effects - pre and post synaptic inhibition |
PRESYNAPTIC (axo-axonal) INHIBITION -decrease transmitter release from terminals in spinal cord POSTSYNAPTIC (recurrent) INHIBITION E.g. dopa overactivity in caudate putamen activates GABA -> inhibits dopa firing e.g. axon of pyramidal cell activates GABA activity-> inhibits pyramidal cell firing Drugs: GABA Ags increase recurrent inhibition e.g. muscimol
|
|
|
Benzodiazepines (BZD) - Overview + Binding |
Clinical use? Anxiolytic, hypnotic, sedative, anticonvulsant, muscle relaxant e.g. diazepam, midazolam, clonazepam BINDING properties - high affinity, spec, saturable, stereospec BZD high displacement capacity=> high clinical efficacy areas of high BZD bind sites => areas w high level GABA activity Bind sites - alpha subunit of GABAa receptor and interface of alpha+gamma subunits (BZDs act as allosteric modulators here -> increase GABA activity) GABA DOESN’T displace BZDs vice versa!!! GABA facilitates BZD binding to receptor vice versa!!! |
|
|
Benzodiazepines (BZD) Receptor Drugs |
BZD RECEPTOR AGs +ve allosteric modulators -increase GABA activity -> anxiolytic, anticonvulsant => treat anxiety, seizures e.g. diazepam, clonazepam BZD RECEPTOR INVERSE AGs -ve allosteric modulators => opp effect to ags above e.g. beta-carbolines, FG-7142 BZD RECEPTOR PARTIAL AGs -cant produce max response => good anxiolytic but bad sedative e.g. bretozenil, abercarnill BZD RECEPTOR ANTAGs e.g. Ro-15-1788 - blocks binding+ effects of ags+inverse ags e.g. flumazenil - anaesthesia Treat conditions: -epilepsy, anxiety, muscle spasm -used as sedation+anaesthetic Side effects: -excessive sleepiness, confusion, memory issues, increased anxiety + aggression, habituation (withdrawal syndrome) |
|
|
Excitatory Amino Acid Neurotransmission- Glutamate Receptors |
METABOTROPIC (mGluR G-protein) Group 1 - mGlu1+5 -> Gq couples -> increase PLC/IP3/DAG activity - act as postsynaptic membranes -> when acticvated => increase ion conductance + inhibitory postsynaptic potentials Group 2 +3 - mGlu2+3, mGLu4,6,7,8 -> Gi/ o coupled -> decrease adeylyl cyclase/cAMP activity -act at presynaptic membrane to inhibit firing mGLuR functions - mGlu1 expression treat cancer, mGlu2+3 ags treat schizo, mGlu4 R activation treats Parkinsons IONOTROPIC (iGLuR - ion channel) Receptor classes - NDMA, AMPA, kainate, delta AMPA + kainate receptors - carry put fast excitatory synaptic transmission Delta receptors - don’t cause channel opening, funcs include synaptogenesis, synaptic plasticity, motor coordination |
|
|
Excitatory Amino Acid Neurotransmission - Ionotropic receptors cont (NMDA Receptors) |
Treat: Epilepsy - NMDA antags = anticonvulsatns => prevent seizures excitotoxicity => prevent apoptosis Alzheimers -> e.g. MK801 blocks long term potentiation => treat memory loss Schizo - caused by high functioning glutamate receptors => need to inhibit their action to treat schizo Non-favoured funcs: e.g. ketamine - NMDA receptor antag causes vivid dreams in adults e.g. PCP - NMDA receptor antag produces hallucinations + schizo like symptoms |
