L5 - basic concepts in neuropharmacology

Question 1

what affects the fraction of receptors in the R* state

Answer 1

drugs

Question 2

receptor with constitutive activity

Answer 2

no ligand bound but equilibrium lies more towards activated state

Question 3

non-zero baseline on graph

Answer 3

shows receptor with constitutive activity

Question 4

agonist ligand - greater affinity for…

Answer 4

R* state (activated)

Question 5

full receptor agonists reach

Answer 5

receptor saturation

Question 6

inverse agonist

Answer 6

equilibrium held towards R state

Question 7

antagonist ligand

Answer 7

prevents ligand binding therefore no downstream signalling

reversible or irreversible

Question 8

reversible antagonist ligand

Answer 8

competes for agonist binding site

reversible binding

Question 9

irreversible antagonist ligand

Answer 9

change conformation of receptor
reduces ability of agonist to bind
strong covalent bond - remains bonded until internal recycling

Question 10

affinity

Answer 10

how well a drug binds to its receptor

Question 11

efficacy

Answer 11

how well a receptor-bound drug elicits a response

Question 12

potency

Answer 12

amount of drug required to elicit a response

Question 13

allosteric modulators

Answer 13

impact receptor function by binding at an alternative receptor site

Question 14

2 binding sites

Answer 14

orthosteric (enogenous)

allosteric site

Question 15

how do you change the affinity of the orthosteric ligand

Answer 15

elicit conformational change of receptor so drug binds more/less easily

Question 16

positive allosteric modulation

Answer 16

binding of ligand to receptor enhances signalling

Question 17

when you change the efficacy of the orthosteric ligand

Answer 17

binding is unaffected

downstream signalling is affected (potential larger maximal response)

Question 18

neurotransmitter

Answer 18

biochemical that mediates fast-acting direct communication between two neurons

Question 19

neuromodulator

Answer 19

biochemical that modulates activity of neurons and neural networks by changing the ability of neurons to respond to neurotransmitters

Question 20

examples of amino acid neurotransmitters

Answer 20

glutamate
gaba
glycine
aspartate

Question 21

exmaples of biogenic amine neurotransmitters

Answer 21

ACh
histamines
monoamines

Question 22

types of monoamine neurotransmitters

Answer 22

serotonin

catecholamines (dopamine, adrenaline, noradrenaline)

Question 23

how does nitric oxide signalling modulate neurotransmission

Answer 23

Ca2+ influx downstream of ion channel
causes activation of nNOS
increased intracellular NO concentration

Question 24

nNOS

Answer 24

neuronal Nitric Oxide Synthase

Question 25

glial cells release transmitters that modulate neurotransmission

Answer 25

gliotransmitters | neurotransmitters

Question 26

ionotropic receptors

Answer 26

ligand gated ion channels transmembrane mediate fast-transmission (open quickly)

Question 27

examples of ionotropic receptors

Answer 27

nicotinic ACh R 5-GT glycine receptors

Question 28

ionotropic glutamate receptors

Answer 28

NMDA AMPA Kainate

Question 29

NMDA receptor

Answer 29

ionotropic glutamate receptor with Mg2+ block

Question 30

glycine is an +ve allosteric modulator to.....

Answer 30

NMDA

Question 31

metabotropic receptors

Answer 31

couple via 2nd messengers GPCR, RTK indirectly open ion channels 2nd fastest

Question 32

when ligand binds to RTKs

Answer 32

transautophosphorylation at Tyr residues | SH2 domains recruited

Question 33

cytokine receptors

Answer 33

-ve feedback bind to cytokines and transduce their signals cytokines are neuromodulators slower transmission

Question 34

put the receptors in order of speed of transmission | x4

Answer 34

ionotropic metabotropic cytokine hormone

Question 35

hormone receptors

Answer 35

e.g. glucocorticoid/oestrogen receptor

Question 36

when does receptor desensitisation occur | x2

Answer 36

at high levels of agonist exposure | due to chronic exposure to agonist ligand

Question 37

mechanisms causing reduced response to ligand binding to receptor (receptor desensitisation) x3

Answer 37

uncoupling receptor internalisation reduced receptor expression

Question 38

receptor desensitisation can lead to....

Answer 38

drug tolerance

Question 39

arrestins effect on GPCRs

Answer 39

proteins that mediate homologous desensitisation of GPCRs | cause uncoupling and receptor internalisation

Question 40

tachyphylaxis

Answer 40

acute sudden decrease in response to drug after administration

Question 41

tolerance

Answer 41

decreased response to drug after chronic use

Question 42

addiction

Answer 42

behavioural manifestation of tolerance