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Neuropharmacology Of Addiction > Chemistry Of Neurotransmitters > Flashcards

Chemistry Of Neurotransmitters Flashcards

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
Q

Explain the process of GABA recycling

A

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.

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26
Q

What are the 5 sites on the GABA receptor?

A

Picrotoxin, barbiturate, GABA, steroid, benzodiazepine

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27
Q

What is the effect of alcohol and anti-anxiety medications on GABA receptors?

A

It stimulates them

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28
Q

Epileptic seizures are a result of having a deficiency of which NT?

A

GABA

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29
Q

Why are diffuse modulatory systems targets of drugs?

A

They modulate brain states like mood, arousal, and sleep

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30
Q

Why is acetylcholine considered separately as a NT?

A

It is neither an amino acid or modified from one

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31
Q

Where is ACH excitatory?

A

Neuromuscular junctions and autonomic nervous system synapses

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32
Q

ACH receptors also bind what?

A

Nicotine

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33
Q

Where are ACH neurons found in the brain?

A

Brainstem and basal forebrain

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34
Q

What is the brain ACH system involved in?

A

Sleep, attention, and memory

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35
Q

Defects in ACH transmission are seen in what diseases?

A

Alzheimer’s and Parkinson’s

36
Q

What enzyme converts Acetyl CoA and choline into ACH?

A

CHAT

37
Q

What enzyme degrades ACH?

A

ACHE, acetylcholinesterase

38
Q

What often targets the AchE enzyme?

A

Drugs used to treat neuromuscular diseases like Alzheimer’s & some animal venoms, insecticides and chemical weapons

39
Q

What is the effect of a-bungarotoxin on ACH receptors?

A

Blocks them irreversibly

40
Q

What are the 5 biogenic amines?

A

Serotonin, dopamine, norepinephrine, histamine, epinephrine

41
Q

What are the monoamines?

A

Dopamine, norepinephrine, epinephrine, and serotonin

42
Q

Which NTs are catecholamines?

A

Norepinephrine, epinephrine, and dopamine

43
Q

What two features must a NT have to be considered a catecholamine?

A

A catechol group and an amino group

44
Q

The dopamine catecholamine pathway in the brain involves what regions?

A

Neurons found in substantia nigra and VTA

45
Q

Norepinephrine catecholamine pathway in the brain involves mainly what region?

A

Locus coeruleus

46
Q

Epinephrine catecholamine pathway in the brain involves what region?

A

Medullary epinephrine neurons

47
Q

What is the enzyme that converts tyrosine to L-DOPA?

A

TH, tyrosine hydroxylase

48
Q

What enzyme converts dopamine to norepinephrine?

A

DBH, Dopamine B-Hydroxylase

49
Q

What enzyme converts norepinephrine to epinephrine?

A

PNM

50
Q

What is the precursor of all catecholamines?

A

Tyrosine

51
Q

What enzyme converts L-DOPA to dopamine?

A

AAAD

52
Q

What cofactors are needed for the conversion of L-tyrosine to L DOPA?

A

Iron 2, BH4, O2

53
Q

Dopamine, EPI, NOR, histamine, and serotonin are transported into vesicles by what?

A

VMAT; non-selective for amines

54
Q

What cofactors are needed to convert dopamine into norepinephrine?

A

Ascorbic acid & O2

55
Q

Which catecholamine is synthesized in vesicles?

A

Norepinephrine

56
Q

TH is unique to what types of neurons?

A

Catecholamine-containing neurons

57
Q

What is the rate limiting step of catecholamine synthesis, and what cofactor is the most important?

A

TH is RLS, BH4 most important

58
Q

Where is the ubiquitous enzyme AAAD found?

A

In the cytoplasm

59
Q

Where is DBH located and why?

A

Inside vesicles, synthesis of NOR happens here

60
Q

Where is PNMT located and why?

A

In the cytoplasm, epinephrine is made outside the vesicle and then brought in later

61
Q

What are the roles of dopamine?

A

Coordination of movement, motivation, reward, reinforcement

62
Q

What are the 3 methods of removal of dopamine from the synaptic cleft?

A

1) DAT, dopamine active transporter
2) MAO enzyme
3) COMT enzyme

63
Q

MAO inhibitors treat what diseases?

A

Depression & Parkinson’s

64
Q

COMT enzyme inhibitors treat what disease?

A

Parkinson’s

65
Q

What are the roles of norepinephrine?

A

Sleep, wakefulness, arousal, attention, and feeding

66
Q

What enzymes are involved in the degradation and removal of norepinephrine?

A

1) NET, norepinephrine transporter
2) MAO
2) COMT

67
Q

What is the role of epinephrine?

A

Acts on cardiovascular tissues, fight or flight

68
Q

What enzymes are involved in the degradation of epinephrine?

A

1) NET
2) MAO
3) COMT

69
Q

What are the roles of serotonin?

A

Sleep, wakefulness, depression, anxiety

70
Q

What is the precursor for serotonin?

A

Tryptophan

71
Q

What enzyme converts tryptophan to serotonin?

A

Tryptophan 5 hydroxylase

72
Q

What are the methods of reuptake/degradation of serotonin?

A

Reuptake by serotonin transporter (SERT), degradation by MAO

73
Q

How does Prozac treat depression?

A

Prevents serotonin reuptake by blocking the SERT transporter

74
Q

Many neuropeptides are also what?

A

Hormones

75
Q

Neuropeptides have general roles in what?

A

Emotion, pain, stress, homeostasis

76
Q

True or false: neuropeptides and small molecule neurotransmitters are colocalized together

A

True

77
Q

What are the 3 endogenous opioid peptides?

A

Endorphins, enkephalins, dynorphins

78
Q

To which general class of neurotransmitters do opioids belong?

A

Neuropeptides

79
Q

What are opioids co-localized with?

A

GABA, serotonin

80
Q

What are the effects of opioids on the human body?

A

Control of pain and tend to be depressants

81
Q

What are the steps of synthesis of peptide NTs (how opioids would be synthesized)?

A

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
Q

Run through the steps of neuropeptides transport and storage

A

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
Q

What type of NTs have no mechanism for reuptake?

A

Neuropeptides, inactivated by peptidases which cleave them into amino acids

84
Q

What types of NTs have both ionotropic and metabotropic receptors?

A

Amino acid transmitters, ACH, and serotonin; all the rest are metabotropic

85
Q

Are autoreceptors ionotropic or metabotropic?

A

Metabotropic

86
Q

What are the two most common mechanisms utilized by autoreceptors?

A

1) inactivation of calcium channels

2) inhibition of synthetic enzymes such as TH

Neuropharmacology Of Addiction (8 decks)

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