Neuropharmacology Flashcards
1
Q
What is a neurotransmitter?
A
released by presynaptic terminals and produce rapid excitatory or inhibitory responses in postsynaptic neurons
2
Q
Give examples of fast neurotransmitters?
A
glutamate; GABA
3
Q
What type of channel do fast neurotransmitters operate through?
A
ligan-gated ion channels
4
Q
What are neuromodulators?
A
released by neurons and by astrocytes, produce slower pre- or post-synaptic responses, indirectly modulate the probability of other ion channels opening in response to voltage changes
5
Q
What are neurotrophic factors?
A
released mainly by non-neuronal cells and act on tyrosine kinase-linked receptors that regulate gene expression and control neuronal growth and phenotypic characteristics
6
Q
How do slow neurotransmitters and neuromodulators work?
A
through GPCRs
7
Q
Give examples of agents which work as both neurotransmitter and modulator, using both ion channels and GPCRs?
A
glutamate; 5-HT; ACh
8
Q
What is a psychotropic drug?
A
drug that affects mood and behaviour
9
Q
What is the principal excitatory transmitter in the CNS?
A
L-glutamate
10
Q
What is the action of memantine?
A
NMDA-antagonist
11
Q
How is glutatmate in the CNS synthesised?
A
mainly from glucose via Kreb cycle or glutamine synthesised by glial cells
12
Q
What are hte main inhibitory amino acids?
A
GABA; glycine
13
Q
How are fast neurotransmitters stored?
A
synaptic vesicles
14
Q
How are neurotransmitters released from synaptic vesicles?
A
calcium dependent exocytosis
15
Q
What happens glutamate taken up by astrocytes
?
A
converted to glutamine
16
Q
Give an example of an ionotrophic receptor?
A
ligand-gated ion channel
17
Q
Give an example of a metabotrophic receptor?
A
GPCR
18
Q
What are the 3 types of glutamate receptor?
A
NMDA; AMPA and kainate
19
Q
How many types of subunit are NMDA receptors made from?
A
7
20
Q
What is the function of the dendrites of a neurone?
A
receive inputs from other neurones and convey graded electrical signals passively to the soma
21
Q
Where is the site of initiation of the AP in the neurone?
A
axon hillock and initial segment
22
Q
Give an example of a unipolar neurone?
A
peripheral autonomic neurone
23
Q
Give an example of a pseudounipolar neurone?
A
dorsal root ganglion neurone
24
Q
Give an example of a bipolar neurone?
A
retinal bipolar neurone
25
Give an example of a multipolar neurone?
lower motor neurone
26
What are the 4 functional regions of neurones?
input; integrative; conductile; output
27
What defines the distance over which a current spreads thorugh the axon?
membrane resistance and axial resistance of the axoplasm
28
What is the most common type of synapse?
axodendritic
29
What is the least common type of synapse?
axoaxonic
30
Where do vesciles containing neurotransmitter cluster presynaptically?
around the active zones
31
Where are the neurotransmitter receptors found in greatest numbers postsynpatically?
postsynaptic density
32
What effect does glutatmate release have on the post-synaptic terminal?
causes influx of sodium, resulting in an epsp
33
What effect does GABA have on the postsynaptic cleft?
chloride release and an ipsp
34
What is the difference between spatial and temporal summation in synaptic integration?
spatial: many inputs determine the output whereas temporal- AP frequency of one single input determines outpu
35
What are peptides released from?
secretory vesicles
36
Why is the synthesis of glycine and glutatmate different to GABA and amines?
glycine and glutamate are amino acids foudn in every cell whereas GABA and amines aren't
37
What type of receptor is GABAa?
ligand-gated ion channel
38
What type of receptor is GABAb?
GPCR
39
Where are GABAa receptors mainly located in the synapse?
post-synpatically
40
How do GABAb receptors work?
inhibit voltage gated Ca channels to reduce trasmitter release and increase potassium conductance both pre- and post synaptically
41
How do GABAa receptors work?
allow chloride into neurone, hyperpolarising it
42
What is long term potentiation?
prolonged enhancement of synaptic transmission that occurs at various CNS synapses following a short burst of high-freq presynaptic stiulation
43
What does activation of NMDA receptors require?
binding of both glutamate and glycine
44
What is the general structure of ionotropic glutamate receptors?
tetramer
45
What is the general difference between NMDA and AMPA receptors in terms of effector mechanism?
NMDA: slow kinetcs with high Ca permeability whereas AMPA have fast kinetics with low Ca permeability
46
What ion blocks NMDA receptors?
Mg
47
How do BZDs act on GABA receptors?
bind to an accessory site (BZD receptor) on GABAa
48
What receptor does baclofen work on?
GABAb
49
Where is glycine found in particularly high concentrations?
spinal cord
50
What neurotransmitter is affected by tetanus toxin?
prevents glycine release at inhibitory interneurons resulting in excess reflex hyperexcitability and spasms
51
How is GABA made?
from glutamate by glutaminc acid decarboxylase
52
What are the principal amine transmitters?
5-HT; ACh; dopamine
53
Where is the most prominent cluster of NA cell bodies?
locus coeruleus in the pons
54
What type of receptor are adrenoceptors?
GPCR
55
What are the functions of noradrenergic transmission?
arousal system; blood pressure regulation and control of mood
56
Give examples of drugs which act of noradrenergic transmission in the CNS?
antidepressants; cocaine; amphetamine
57
Where is dopamine foudn in the highest quantities in the brain?
corpus striatum
58
What are the 4 main dopamine pathways in the brain?
1- nigrostriatal pathway
2-mesolimbic pathway
3-mesocortical pathway
4- tuberohypophyseal
59
What is theanatomy nigrostriatal pathway?
cell bodes in the substantia nigra with axons terminating in the corpus striatum
60
Where are the cell bodies for the medolimbic pathwya?
midbrain ventral tegmental area
61
Where do neurones from the ventral tegmental area project to?
nucleus accumbens and amygala
62
What is the anatomy of hte mesocortical pathway?
cell bodies in the ventral tegmental area projecting to the frontal cortex
63
What is the tuberhypophyseal pathway?
hypothalamus to pituitary
64
What are the two families of dopamine receptors?
D1 and D2
65
Which receptors does D1 family include?
D1 and D5
66
Which receptors does D2 family include?
D2,D3 and D4
67
Which dopamine receptors are most abundant?
D1
68
Where are D1 receptors found?
areas receiving dopamine innervation e.g striatum; limbic system; thalamus and hypothalamus
69
Where are D2 receptors found?
same as D1 plus pituitary gland; act as inhibitory auto-regulators
70
Where are D3 receptors found?
limbic system but not striatum
71
What receptor is dopamine action in the periphery mediated by?
D1
72
What type of dopamine receptor in found in the vomiting centre?
D2
73
What other neurotransmitter does dopamine act as a precursor for?
NA
74
What is the general function of the nigrostriatal pathway?
motor control
75
What is the general function of dopamine in the mesolimbic pathway
emotion and drug-indicued reward
76
Waht is the general function of the mesocortical pathway?
emotion
77
What type of GPCR are D1 type receptors linked to?
Gs
78
What does Gs activation cause?
activation of adenylyl cyclase
79
What type of GPCR are D2 type receptors linked to?
Gi/G0
80
What does Gi/G0 activation cause?
inhibits adenylyl cyclase; activates K channels, inhibits Ca channels and may activate phospholipase C
81
What is the relationship of D1 and D2 type receptors to SZ?
D1: negative symptoms; D2: positive symptoms
82
What is the degredation product of serotonin that is excreted in hte urine?
5-HIAA
83
What are the raphe nuclei?
cell bodies of 5-HT which are grouped in the pons and upper medulla close to midline (raphe)
84
What type of receptor are serotonin receptors?
GPCR except for 5-HT3 which is ion channel
85
Give an example of a 5-HT1D receptor agonist?
sumatriptan
86
Give an example of a 5-Ht3 receptor antagonist?
ondansteron
87
What are the Gq coupled ACh receptors?
M1,M3 and M5
88
What are the Gi/Go coupled ACh receptors?
M2 and M4
89
What is the action of Gq coupled ACh receptors?
excitation thorugh blockade of M-type K channels
90
What is the action of Gi/Go coupled ACh receptors?
inibitory thorugh activation of potassium channels and block Ca channels
91
Where are nicotinic ACh receptors found usually in the CNS?
presynaptically
92
What is the funciton of nACHRs
usually to facilitate the release of other transmitters
93
Which type of ACH receptor (muscarinic or nicotinic) is more important in CNS function?
muscarinin
94
What function do nACHRs mediate that mACHRs dont?
behavioural arousal
95
What type of histamine receptor antagonist are anti-emetic?
H1
96
What is the general function of adenosine?
inhibitory (caffeine is an antagonist of A2 receptors and increases wakefulness)
97
What is misfolding?
abnormal conformations of proteins such that they tend to form large insoluble aggregates
98
How does glutatmate cause excitotoxicity?
activates NMDA; AMPA and metabotropic receptors. Activation of AMPA depolarises the cell; unblocks NMDA receptors, permitting Ca entry. and opens Ca receptors, releasing more glutamate. metabotropic receptors cause release of intracellular Ca. Na entry causes more Ca entry. Depolarisation inhibits glutamate uptake- lots of glutamate in extracelllular space
99
What ion is central to excititotoxicity?
calcium
100
What are the functions of raised calcium?
increased glutamate release; activation of proteases and lipases which damage the membrane; activation of nitric oxide; increased arachidonic acid release
101
What type of glutamate receptor is excitotoxicity mainly associated with?
NMDA
102
What is found extracellularly in Alzhemiers?
amyloid plaques
103
What is found within the neurones in Alzhemiers?
neurofibrillary tangles
104
What are the amyloid plaques in Alzhemiers made of?
beta-amyloid protein
105
What are the neurofibrillary tangles made of?
filaments of phosphorylated form of microtubule associated protein- Tau
106
What is the precursor of amyloid protein?
amyloid precursor protein
107
Which chromosome is amyloid precursor protein found on?
21
108
What is the characteristic transmitter system loss in AD?
loss of cholinergic neurons in the basal forebrain nuclei
109
Where do the mutations involved in familial AD lie?
in APP gene or presenillin gene (both increase beta-amyloid protein
110
What condition is amantadine used to treat?
Parkinsons
111
What is the action of amantadine?
act by releasing dopamine
112
What are the slowly-developing side effects of levodopa?
dyskinesia (within 2 years of therapy); rapid fluctuations in clinical state
113
What is the action of domperidone?
dopamine antagonist in the chemoreceptor trigger zone but doesnt access basal ganglia
114
What other drug is given with levodopa and why?
inhibitor of peripheral dopa decarboxylase e.g carbidopa to reduce SE
115
What amino acid is huntingtin composed of?
glutamine
116
What is thought to be the cause of hyperactivity of dopaminergic synapses?
loss of GABA-mediated inhibition of the basal ganglia
117
What is use-dependence, a feature of anti-epileptic drugs?
block preferentially the excitation of cells that are firing repetiively, and have higher block with higher frequency
118
How does use-dependence arise?
preferential binding to channels in inactivated state ( just after depolarisation)
119
What channel is thought to be invovled in absence seziures?
calcium channels
120
What is antipyschotic potency realted to?
activity on D2 receptors
121
What is the activity of tricyclic antidepressants?
block noradrenaline and 5-HT reuptake
122
What controls the discharge of hypothalamic cells?
noradrenergic and 5-HT inputs
123
What type of seizure are sodium channel blockers used in
partial and secondarily general seizures
124
What are T-type calcium channels?
normally depolaried and inactive in the awake state
125
What seizure are T type Ca channels implicated in?
absence seizures
126
What is the function of voltage operated caclium channels?
control caclium entry into neuronal terminals and regulate neurotransmitter release
127
What is the common side effect to sodium channel inhibitors?
SJS
128
What are the side effects of lamotrigine?
sleep disturbances, hallucinations and occasioanl increases in seaizure frequeny
129
What is the kinetics of phenytoin?
zero-order
130
What is the mechanism of carbamazepine?
Na channel inactivation
131
What is the actions of valproate?
sodium; T-Ca channels inactivation/ block and GABA channel activation
132
What are the actions of lamotrigine?
Na channel and voltage Ca channel block
133
What is the action of phenytoin?
sodium channel inavtication
134
What are the actions of gabapentin?
voltage Ca channel block and glutamate channel inhibition
135
What is the step that results in GPCR inactivation?
GTP hydrolysis
136
What is the action of Gs receptors?
activate adenylyl cyclase
137
what is the action of Gq receptors?
stimulates phospholipase C
138
What is the action of Gi receptors?
inhibits adenylyl cyclase
139
What is the function of adenylyl cyclase?
catalyses formation of cAMP
140
What is the major effect of cAMP?
to activate protein kinase A
141
How is cAMP broken down?
phosphodiesterase
142
What is the action of phospholipase C?
cuts PIP2 to generate IP3 and DAG
143
What is the function of IP3?
opens ligand gated Ca channels on the endoplasmic /sarcoplasmic reticulum
144
What is the function of DAG?
activates protein kinase C
145
What binds to GPCRs in desensitisation?
beta-arrestin
