Basic Neuropharmocology Flashcards
Neuropharmocology
Effect of drugs on the nervous system
Drugs: chemical substance, known structure, not a nutrient or other essential dietary ingredient, administered to living organism, biological affect.
Synthetic or endogenous
Molecular
Behavioural
Psycho
drug target proteins
receptors
ion channels
enzymes
transporters
target protein expession
expressed along the neuronal cell
- density change per place
- differential expression how drug expressed depending on what part of cell
protein targets: receptors
- protein molecule with function to recognise and respond to endogenous chemical signals
- macromolecules where drugs interact are drug targets
- affinity: likeliness of ligand molecule to bind to receptor at a particilar concetration
types of receptor proteins
agonist: activates a receptor. can be direct or use transdunction mechanisms (g-coupled protein).
direct = closing/opening of ion chanels
transduction mechamisms = enzyme activation/inhibition, DNA transcription, ion channel modulation
antagonist: binds to receptor but doesnt activate it. makes it so agonist cant bind. endogenous mediators blocked (no effect)
competitive = bind to binding site so agonist cant (allosteric agonist)
non-competitive = other site on protein so agonist cant bind/work (allosteric antagonist)
protein targets for drugs: ion channels
- movements of ions in and out of membranes
- neuron homeostasis and generating AP
- most ion channels ligand/voltage gated - only open with these
types of drug targets ion chanels
- blockers: blobks ion cahnnel pores prevent ion movcement
- modulators: dont block but increase/decrease opening probability
protein targets for drugs: enzymes
- enzymes important for neural transmission: break down neurotransmitters in synapse so not overloaded and new AP
- ie monamine oxidase for seratonin, dopamine, norepinephrine. inhibitors are first type of antidepressant
types of enzymes for drug targets
- inhibitors: normal reaction inhibited
- false substrate: abnormal metabolite produced
- prodrug: active drug produced
protein targets for drugs: transporters
- transporters facilitate movements of ions and snall organic molecules accross membranes
- most rely on ATP active transport/secondary active transport to move across electrochemical gradient
- important role in reuptake of neurotransmitters in synapse
types of transporters for drug targets
inhibitor: antagonist block binding site or stop normal transport. blocks transport from happening
false substrate: abnormal compound accumulated
ion channel and receptor expression
- ion channels in every somain across neuron
- ion channels important for forward/backward propagation of electric potentials in neurons
- therefore drugs/toxins that affect ion channels can affect multiple neuronal functions
drug targets on synapse
- synapse between presynaptic and postsynaptic neuron
- protein targets at synapse: all (both ligand and voltage ion channels)
tripartite synapse
pre and postdynaptic neuron have the synapse surrounded by astrocyte end feet.
end feet release chemicals and have ion channels receptors ect
quadpartite synapse
- microglia = immune cells of brain
- role in synapse: express transporters, ion channels, receptors
- therefore drugs can affect multiple cells at a synapse
electrical synapse
- aka gap junctions
- has protein channels that allow bidirectional flow of ions, metabolites, 2nd messengers and small molecules
- direct communication between 2 neurons
- no delay in transmission and allows cells/circuts to couple with eachother
composed of 2 hemichannels (one on each neuron) make intercellular channel - occur in diff locations across neuron
some synapses have electro + chem (mixed) - location of electrical synapse affect electric activity of both neurons
hemichannels
- hemichanneels formed by connexin in vertibrates, innexin in invertibrates
some mammals have pannexin but less common than connexin - occur at diff locations across neuron
volume transmission
- some circuts have excess neurotransmitters that escape synapse
- can affect nearby cells
- volume transmission = widespread mode of intercellular communication occurs in extracellular fluid and cerebrospinal fluid of brain with VT signals moving from source to target cells via energy gradients leading to diffusion and convection (flow)
pure spill over transmission
- communication between 2 cells is solely due to excess release of neurochemical or molecule
- v few examples in nervous system
