Neuropharmacology Intro

Question 1

Cholinergic transmission is important for

Answer 1

cognitive function, sensitization to incoming stimuli, movement control

Question 2

Describe the difference between nACh receptors and mACh receptors.

Answer 2

nAch receptors are ligand gated cation channels whereas mACh receptors are GPCRs

Question 3

Where are cholinergic neurons?

Answer 3

concentrated in the basal forebrain and pons, but numerous cholinergic interneurons are found int he cortex and basal ganglia

Question 4

Dopamine transmission is important for

Answer 4

natural rewards and motor function

Question 5

Problems in dopamine transmission is implicated in diseases or disorders such as

Answer 5

schizophrenia, parkinsons disease, addiction, depression and ADHD

Question 6

Two varieties of GPCR dopamine receptors

Answer 6

D1-type (D1 and D5) and D2-type (including D2, D3, and D4)

Question 7

Where are dopamine neurons?

Answer 7

situated in the midbrain, either the ventral tegmental area or the substantia nigra pars compacta

Question 8

Norepinephrine activates

Answer 8

adrenergic receptors (GPCRs), ainly alph1 and/or alpha2 in the CNS

Question 9

NE is involved in

Answer 9

memory, pain transmission, and salience

Question 10

NE transmission is altered in

Answer 10

depression and addiction

Question 11

NE neurons are located in

Answer 11

the pons, specifically the locus coeruleus

Question 12

Serotonin activates

Answer 12

either 5-HT3 ligand gated cation channels, or GPCR-type 5-HT receptors

Question 13

Serotonin is important in

Answer 13

reward, learning, and mood/affect, and is thought to play a major role in depression and possibly schizophrenia

Question 14

Where are serotonin neurons located?

Answer 14

in the midbrain/pons, specificially inthe raphe

Question 15

GABA is produced from

Answer 15

glutamate

Question 16

Major inhibitory neurotransmitter in the CNS

Answer 16

GABA

Question 17

GABA activates

Answer 17

GABAA type ligand gated Cl- channels, and GABAB and GABAC receptors which are GPCRs

Question 18

Where is GABA produced?

Answer 18

produced throughout the brain by numerous cell types, and is altered in many disorders, including epilepsy, muscle spasticity, and addictions such as alcoholism

Question 19

Main excitatory neurotransmitter in the brain

Answer 19

Glutamate

Question 20

What does glutamate bind to?

Answer 20

Ion channels (AMPA, NMDA) and GPCRs (mGluRs)

Question 21

Glutamate may be a useful pharmacologic target in which diseases?

Answer 21

epilepsy and schizophrenia

Question 22

Two categories of ligand-gated

Answer 22

ion channels and G protein coupled receptors

Question 23

HCN channels are

Answer 23

cyclic nucleotide-gated channels

Question 24

Ligand that modifies HCN channels

Answer 24

cAMP or cGMP

Question 25

Describes what happens when a GIRK channel is activated

Answer 25

activating a GPCR coupled to a GIRK channel results in enhanced outward K+ currents, which serve to hyperpolarize the membrane potential and keep the cell “clamped” near the equilibrium potential for K+, which is around -90mV

Question 26

Where are NT transporters usually located?

Answer 26

usually located presynaptically where they remove NT molecules from the synaptic cleft and return them back inside the presynaptic terminal

Question 27

Which ion do most neurotransmitter transporters use?

Answer 27

most are Na+ symporters, making them electrogenic

Question 28

How is electrical activity altered by drugs

Answer 28

by directly affecting the function of ion channels, or indirectly by changing the overall number or function of important targets in the CNS

Question 29

Where do drugs act?

Answer 29

NT synthesis, NT storage, NT reuptake, autoreceptors, presynaptic receptors, postsynaptic receptors

Question 30

What will decreasing the action of NT transporters do?

Answer 30

will decrease re-uptake, and therefore prolong the action of drugs released into the synaptic cleft

Question 31

Difference between blocking a presynaptic autoreceptor versus a postsynaptic receptor.

Answer 31

Blocking an inhibitory autoreceptor on the presynaptic side will increase activity of the synapse whereas blocking a receptor on the postsynaptic side can decrease the output of a synapse

Question 32

BBB formed by

Answer 32

tight junctions between endothelial cells, which contributions from astrocytes as well

Question 33

BBB typically restricts

Answer 33

microscopic objects (bacteria, viruses) and hydrophilic molecules, but allows small hydrophobic molecules (hormones, gases) and glucose

Question 34

Two ways drug affinity for receptors is measured

Answer 34

saturation assays and competition assays

Question 35

Describe saturation assays

Answer 35

directly measures drug affinity for receptor, but require the test drug to be radiolabeled, therefore a large amount of prior knowledge about the drug and its candidate receptor must be in hand

Question 36

What is Kd?

Answer 36

the concentration of the radioligand where 50% of receptors are bound

Question 37

What is Bmax?

Answer 37

the total number of receptors in a preparation

Question 38

Describe competition assays

Answer 38

they’re done with a known, labeled drug and unlabeled test drugs which are used to compete off the labeled drug. Provides an indirect assessment of affinity of the drug for the receptor because it is measuring how well it can displace the labeled drug

Question 39

What is the Ki?

Answer 39

the concentration of drug where 50% of the radioligand is displaced

Question 40

Functional Assays

Answer 40

Biochemical: enzyme function
Second messenger response assay
Transporter function assay: uptake and/or efflux assay
Patch clamp electrophysiology (ion channel function)

Question 41

Describe patch clamp electrophysiology

Answer 41

involves placing a glass pipette onto the surface of the cell expressing the channel of interest, followed by forming a high-resistance seal between the glass and the cell membrane

Question 42

Where do full agonists bind?

Answer 42

binds at the orthosteric binding site where the natural ligand binds, and activates the receptor as well as the natural ligand

Question 43

Where do partial agonists bind?

Answer 43

binds the receptor and activates it, but can never achieve full activation of the receptor population like a full agonist can - also has antagonist activity

Question 44

Where do antagonists bind?

Answer 44

bind at the orthosteric binding site, do not have any ability to actiate the receptr on its own, but will prevent the ability of the natural ligand or an agonist to activate the receptor?

Question 45

What does an inverse agonist do?

Answer 45

reduces the activity of a receptor to levels BELOW what they would be if no ligand is present at all