Chapter 11: Introduction to CNS pharmacology

Question 1

the CNS is made of a network of ___ and ___cells that carry signals throughout the brain and through the body

Answer 1

neurons and supporting cells

Question 2

neurons send signals to each other by release of ___ at synapses

Answer 2

neurotransmitter

Question 3

the actions of neurons are energy intensive and must be tightly regulated to have efficient ___

Answer 3

signal transduction

Question 4

support cells include astrocytes, which are glial cells that help remove __, supply___ and make up part of the ___

Answer 4

neurotransmitter form synapses; nutrients; bbb

Question 5

compared to body BV, vessels entering the CNS are much ___ permeable

Answer 5

less

Question 6

the BBB is made of ___ and ___

Answer 6

endothelial tight junctions and the end feet of astrocytes (aka astroglia)

Question 7

the arrangement of the BBB helps prevent ____ of most polar molecules and ____ are required to bring many required substances such as glucose into the CNS

Answer 7

passive diffusions; transporters

Question 8

what type of molecules are capable of crossing the BBB by passive diffusion?

Answer 8

very small lipophilic

Question 9

does low penetration mean no penetration in the CNS?

Answer 9

no

Question 10

L-DOPA and glucose are very polar molecules, but have higher than expected penetrance of the CNS, why?

Answer 10

they are actively transported in as essential nutrients

Question 11

phenobarbital and phenytoin are very lipophilic drugs, but have lower than expected levels in the CNS, why is this?

Answer 11

they are actively pumped out

Question 12

molecules can generally cross the BBB if they are one or all of what 3 things?

Answer 12

small, hydrophobic, substrate for carrier

Question 13

molecules generally can’t cross the BBB if they are one or more of what 2 things?

Answer 13

large, hydrophilic

Question 14

___ is required to determine if a drug is a substrate for a transporter

Answer 14

experimental data

Question 15

during ___, the BBB becomes more permeable and allows more molecules to cross

Answer 15

systemic inflammation

Question 16

the majority of neuronal activity occurs at ___

Answer 16

synapses

Question 17

NT are made and stored in the ___ nerve terminals

Answer 17

presynaptic

Question 18

___ causes NT to be released into the synapse where it acts on ___receptors

Answer 18

action potential propagation; post-synaptic

Question 19

the signal is terminated as the NT ____

Answer 19

diffuses away from the synapse

Question 20

once the NT difuses away from the synapse, it can be ___ or ___ by ___ or ___ cells

Answer 20

degraded; taken back up by presynaptic or glial cells

Question 21

some signals between neurons may involve the release of a ___ back into the synapse to retrogradely signal to the presynaptic neuron

Answer 21

signalling molecule

Question 22

list some CNS NTs

Answer 22

glutamate, GABA, NE, dopamine, serotonin, endocannabinoids, glycine, neuropeptides, Ach, histamines

Question 23

Glutamate (Glu) is a ___- NT made in ___ and stored in ___

Answer 23

excitatory, presynaptic; vesicles

Question 24

when glutamate is taken up by glial cells its made into ___

Answer 24

glutamine

Question 25

after glial cells turn glutamate into glutamine, what happens to it?

Answer 25

taken back into presynaptic neurone terminals so it can be made into glutamate again

Question 26

what is the primary way a glutamate response is terminated?

Answer 26

glutamate is taken up into glial / astrocyte

Question 27

what is the role of vesicular glutamate transporter (VGLUT)?

Answer 27

packages glutamate into vesicles for future release

Question 28

what are the 2 types of glutamate receptors? what type of receptor are they?

Answer 28

metabotropic and inotropic;p bot ligand gates ion channels

Question 29

metabotropic glutamate receptors on the postsynaptic cell are typically ___ coupled and there activation results in the ___ , giving an overall ___ effect

Answer 29

Gq; closing of K channels; excitatory

Question 30

metabotropic glutamate receptors on the presynaptic cell has a ___ effect bc these are ___ receptors and are __coupled

Answer 30

inhibitory; autoreceptors;GI

Question 31

AMPA and NMDA inotropic glutamate receptors are expressed on ___ cells and are permeable to ___ ions

Answer 31

postsynaptic; cations Ca and K

Question 32

binding of glutamate to inotropic receptors causes ___

Answer 32

membrane depolarization called an EPSP

Question 33

what happens if only a little bit of glutamate is released to inotropic receptors/

Answer 33

only small membrane depolarization and no AP / signal generated

Question 34

GABA is a ____ NT

Answer 34

inhibitory

Question 35

what are the 2 types of GABA receptors?

Answer 35

metabotropic and inotropic

Question 36

inotropic GABA receptors are aka ____ receptors

Answer 36

GABA a

Question 37

metabotropic GABA receptors AKA ____ receptors

Answer 37

GABA b

Question 38

opening of GABA a receptors causes influx of ___ions, resulting in ____

Answer 38

Cl-; hyper polarization and IPSP

Question 39

activation of GABA b receptors causes postsymptic ___channels to open, resulting in ___

Answer 39

K+; hyperolarzation

Question 40

what is the effect of hyperpolarizaytion on AP generation?

Answer 40

makes it harder because it requires greater depolarization to threshold

Question 41

what type of receptors are GABA b receptors?

Answer 41

GPCR

Question 42

the BY subunits of the GABA b receptors interact with ion channels to further ___

Answer 42

reduce excitability of postsynaptic cells

Question 43

many cells receive multiple inputs and the overall response is a ____ of those signals

Answer 43

integration

Question 44

many signals originate in specific brain regions Called __

Answer 44

nuclei

Question 45

when neurons leave a nuclei in the brain, they go many different places, making _____ difficult and often, drugs used in the CNS can have significant ___

Answer 45

drug targeting one region ; side effects

Question 46

the same NT can have many different physiologic effects depending on ____ it is in

Answer 46

brain region

Question 47

most CNS drugs target one of which 5 things?

Answer 47

1. presynaptic excitability 2. NT synthesis 3. NT storage 4. NT release 5. NT. metabolism / reuptake 6. receptor target 7. postsynaptic excitability 9. retrograde signalling

Question 48

amphetamine and cocaine influence the storage and reuptake of ___ in presynaptic neurons

Answer 48

NE

Question 49

amphetamine-like drugs structurally mimic ____ and are good substrates for the transporters to fill up ___ and push NE out casino the NET to allow NE to ___

Answer 49

catecholamines; storage vesicles; release into synapse

Question 50

is an AP required to release NE when amphetamine is involved?

Answer 50

no

Question 51

cocaine blocks the NET, preventing NE ____, resulting in ___

Answer 51

reuptake at the presynaptic neuron; longer duration of action for NE

Question 52

t/f receptors may be more selectively targeted compared to NT

Answer 52

true

Question 53

t/f similar receptor types exist in many brain regions and may result in adverse effects

Answer 53

t

Question 54

many ADR of CNS drugs are related to the drug interacting with similar receptors in the ___ and __

Answer 54

CNS and periphery

Question 55

retrograde signalling pathways can be used influence __

Answer 55

presynaptic neuron excitability

Question 56

how do retrograde signalling molecules work?

Answer 56

made in post, releases to act on pre after initial signal has been processed

Question 57

some effects of retrograde signalling can be __ which ___

Answer 57

reduced excitability of pre neuron; reducing NT further NT release

Question 58

___ are an example of retrograde signalling in CNS

Answer 58

endocannabinoids

Question 59

what are endocannabinoids?

Answer 59

regulatory molecules made by post in response to excitatory inputs

Question 60

activation of glutamate simulates ___ which activates Gq and causes downstream activation of ___

Answer 60

mGluR; DAG lipase

Question 61

DAG lipase is responsible for the production of the endocannabinoid ___, which activates cannabinoid receptors on the presynaptic neuron

Answer 61

2-AG

Question 62

what is the effect on glutamate release if 2-AG binds to CB1 receptor on the presynaptic neuron?

Answer 62

Gi couples, inhibitory and reduce glutamate (so less excitement)

Question 63

endogenous stimulation of neurons is typically ___ and ___, this allows neurons to ___

Answer 63

brief and regulated ; be repeatedly active and responsive to AP

Question 64

neurons like to be active, so if its activity is blocked for a long time, the neuron may ___ to increase ability to regain activity

Answer 64

up regulate their receptor

Question 65

t/f the long-term remodelling effects of neurons receiving too much or not enough signalling can be intentional or impede the therapeutic effect of a drug

Answer 65

t