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Neuropharmacology Of Addiction > Chemistry Of Neurotransmitters > Flashcards

Chemistry Of Neurotransmitters Flashcards

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1
Q

What are the 4 criteria of a NT?

A

1) synthesized and stored in the presynaptic neuron (not actually true)
2) released in response to an AP
3) specific post-synaptic receptors
4) mechanism for removal

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2
Q

What is neurotransmitter modulation?

A

Changing excitability without directly causing an EPSP or an IPSP

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3
Q

What are the stages in the life cycle of a NT?

A

1) synthesis
2) storage
3) degradation possibly
4) release
5) inhibitory feedback by autoreceptors
6) activation of post receptors
7) deactivation

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4
Q

What are the two broad categories of NTs?

A

Small molecule transmitters and neuropeptides

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5
Q

What are the chain lengths of small molecule NTs vs neuropeptides?

A

Small molecule NTs: about 1 amino acid

Neuropeptides: 3-36 amino acids

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6
Q

Which broad category of NT mediates fast, synaptic actions?

A

Small molecule NTs

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7
Q

Which broad category of NTs mediates slower, ongoing synaptic functions?

A

Neuropeptides

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8
Q

Where are small molecule transmitters synthesized?

A

Cytoplasm

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9
Q

Where are neuropeptides synthesized?

A

Inside vesicles

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10
Q

What four amino acids are considered NTs? What are their cell effects?

A

GABA, glycine = inhibitory glutamate, aspartate = excitatory

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11
Q

What is the main inhibitory NT in the Brain?

A

GABA

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12
Q

What is the main inhibitory NT in the spinal cord?

A

Glycine

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13
Q

Glutamate and aspartate receptors conduct which ions?

A

Sodium

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14
Q

To which broad category of NT does glutamate belong?

A

Small molecule NTs

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15
Q

Glutamine becomes glutamate through which enzyme?

A

Glutaminase

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16
Q

Nearly all excitatory neurons in the brain release what NT?

A

Glutamate

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17
Q

Why must glutamate be synthesized in neurons?

A

It can’t cross the BBB

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18
Q

Explain small molecule NT synthesis in glutamatergic neurons

A

Synthesis of glutaminase in the soma, then slow transport of these enzymes down the axon, then NT synthesis and packaging into terminal

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19
Q

Describe the process of turning glutamate back to glutamine

A

Glutamate from the synaptic cleft is transported into a glial cell by the glutamate transporter and within that glial cell the glutamine synthase enzyme converts it to glutamine which is then pumped out of the glia cell by the glutamine transporter and then transported back to the terminal

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20
Q

GABA is synthesized in neurons from what precursor molecule?

A

Glutamate

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21
Q

What enzyme converts glutamate into GABA?

A

GAD, glutamic acid decarboxylase

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22
Q

GABA and glycine channels conduct what ion?

A

Chloride

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23
Q

What types of receptors can bind benzodiazepines?

A

GABA

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24
Q

Explain small molecule NT synthesis in GABAergic neurons

A

Glutamate already present in presynaptic terminal, GAD synthesized in soma and transported by microtubules down the axon, glutamate converted to GABA by GAD

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25
Explain the process of GABA recycling
GABA from the synaptic cleft is taken back into the presynaptic cell by the GABA transporter. GABA is then packaged into vesicles by the GABA vesicular transporter.
26
What are the 5 sites on the GABA receptor?
Picrotoxin, barbiturate, GABA, steroid, benzodiazepine
27
What is the effect of alcohol and anti-anxiety medications on GABA receptors?
It stimulates them
28
Epileptic seizures are a result of having a deficiency of which NT?
GABA
29
Why are diffuse modulatory systems targets of drugs?
They modulate brain states like mood, arousal, and sleep
30
Why is acetylcholine considered separately as a NT?
It is neither an amino acid or modified from one
31
Where is ACH excitatory?
Neuromuscular junctions and autonomic nervous system synapses
32
ACH receptors also bind what?
Nicotine
33
Where are ACH neurons found in the brain?
Brainstem and basal forebrain
34
What is the brain ACH system involved in?
Sleep, attention, and memory
35
Defects in ACH transmission are seen in what diseases?
Alzheimer’s and Parkinson’s
36
What enzyme converts Acetyl CoA and choline into ACH?
CHAT
37
What enzyme degrades ACH?
ACHE, acetylcholinesterase
38
What often targets the AchE enzyme?
Drugs used to treat neuromuscular diseases like Alzheimer’s & some animal venoms, insecticides and chemical weapons
39
What is the effect of a-bungarotoxin on ACH receptors?
Blocks them irreversibly
40
What are the 5 biogenic amines?
Serotonin, dopamine, norepinephrine, histamine, epinephrine
41
What are the monoamines?
Dopamine, norepinephrine, epinephrine, and serotonin
42
Which NTs are catecholamines?
Norepinephrine, epinephrine, and dopamine
43
What two features must a NT have to be considered a catecholamine?
A catechol group and an amino group
44
The dopamine catecholamine pathway in the brain involves what regions?
Neurons found in substantia nigra and VTA
45
Norepinephrine catecholamine pathway in the brain involves mainly what region?
Locus coeruleus
46
Epinephrine catecholamine pathway in the brain involves what region?
Medullary epinephrine neurons
47
What is the enzyme that converts tyrosine to L-DOPA?
TH, tyrosine hydroxylase
48
What enzyme converts dopamine to norepinephrine?
DBH, Dopamine B-Hydroxylase
49
What enzyme converts norepinephrine to epinephrine?
PNM
50
What is the precursor of all catecholamines?
Tyrosine
51
What enzyme converts L-DOPA to dopamine?
AAAD
52
What cofactors are needed for the conversion of L-tyrosine to L DOPA?
Iron 2, BH4, O2
53
Dopamine, EPI, NOR, histamine, and serotonin are transported into vesicles by what?
VMAT; non-selective for amines
54
What cofactors are needed to convert dopamine into norepinephrine?
Ascorbic acid & O2
55
Which catecholamine is synthesized in vesicles?
Norepinephrine
56
TH is unique to what types of neurons?
Catecholamine-containing neurons
57
What is the rate limiting step of catecholamine synthesis, and what cofactor is the most important?
TH is RLS, BH4 most important
58
Where is the ubiquitous enzyme AAAD found?
In the cytoplasm
59
Where is DBH located and why?
Inside vesicles, synthesis of NOR happens here
60
Where is PNMT located and why?
In the cytoplasm, epinephrine is made outside the vesicle and then brought in later
61
What are the roles of dopamine?
Coordination of movement, motivation, reward, reinforcement
62
What are the 3 methods of removal of dopamine from the synaptic cleft?
1) DAT, dopamine active transporter 2) MAO enzyme 3) COMT enzyme
63
MAO inhibitors treat what diseases?
Depression & Parkinson’s
64
COMT enzyme inhibitors treat what disease?
Parkinson’s
65
What are the roles of norepinephrine?
Sleep, wakefulness, arousal, attention, and feeding
66
What enzymes are involved in the degradation and removal of norepinephrine?
1) NET, norepinephrine transporter 2) MAO 2) COMT
67
What is the role of epinephrine?
Acts on cardiovascular tissues, fight or flight
68
What enzymes are involved in the degradation of epinephrine?
1) NET 2) MAO 3) COMT
69
What are the roles of serotonin?
Sleep, wakefulness, depression, anxiety
70
What is the precursor for serotonin?
Tryptophan
71
What enzyme converts tryptophan to serotonin?
Tryptophan 5 hydroxylase
72
What are the methods of reuptake/degradation of serotonin?
Reuptake by serotonin transporter (SERT), degradation by MAO
73
How does Prozac treat depression?
Prevents serotonin reuptake by blocking the SERT transporter
74
Many neuropeptides are also what?
Hormones
75
Neuropeptides have general roles in what?
Emotion, pain, stress, homeostasis
76
True or false: neuropeptides and small molecule neurotransmitters are colocalized together
True
77
What are the 3 endogenous opioid peptides?
Endorphins, enkephalins, dynorphins
78
To which general class of neurotransmitters do opioids belong?
Neuropeptides
79
What are opioids co-localized with?
GABA, serotonin
80
What are the effects of opioids on the human body?
Control of pain and tend to be depressants
81
What are the steps of synthesis of peptide NTs (how opioids would be synthesized)?
1) pre-propeptides synthesized in rough ER 2) packaged into transport vesicles in the golgi 3) broken down into neuropeptides by enzymes in synaptic vesicles
82
Run through the steps of neuropeptides transport and storage
1) synthesis and packaging of propeptides in soma 2) fast transport of vesicles containing the propeptides down the axon 3) final neuropeptide synthesis in the terminal
83
What type of NTs have no mechanism for reuptake?
Neuropeptides, inactivated by peptidases which cleave them into amino acids
84
What types of NTs have both ionotropic and metabotropic receptors?
Amino acid transmitters, ACH, and serotonin; all the rest are metabotropic
85
Are autoreceptors ionotropic or metabotropic?
Metabotropic
86
What are the two most common mechanisms utilized by autoreceptors?
1) inactivation of calcium channels | 2) inhibition of synthetic enzymes such as TH

Neuropharmacology Of Addiction (8 decks)

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