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B&B Week 7 Flashcards > Lecture 37: Catecholamines Part II > Flashcards

Lecture 37: Catecholamines Part II Flashcards

1
Q

What is the inactivation process of catecholamine neurotransmitters?

A
  1. Reuptake into nerve terminals
  2. Metabolic transformation/catabolism
  3. Diffusion out of the junctional cleft and uptake at extraneuronal sites
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2
Q

What are the two major systems for neurotransmitter uptake?

A
  1. Uptake 1
    • refers to the re-uptake of NE into nerve endings
    • uptake process is high-affinity low-capacity system
  2. Uptake 2
    • refers to mechanisms of extra-neuronal uptake
    • uptake processes is a low-affinity, high-capacity system
    • important for removing circulating amines
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3
Q

What is the catabolic pathway of neurotransmitters?

A

MAO (monoamine oxidase) inactivates both circulating and intraneuronal amines
-functons as a “safety valve” to inactivate any excess neurotransmitter that leaks into the synaptic cleft when the neuron is at rest
Two isoenzymes of MAO:
i. MAO-A: substrates for MAO A enzyme = 5-HT, NE and Trypatmine
ii. MAO-B: substrates are Dopamine and Tryptamine

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4
Q

What are the substrates for MAO-B?

A

Dopamine and tryptamine

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5
Q

What are the substrates for MAO-A?

A

Serotonin, NE and tryptamine

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6
Q

Is MAO the only degrading enzyme in the synaptic cleft?

A

No (there is also COMT and aldehyde reductase that breaks down the product of NE+MAO)

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7
Q

Should you target rate limiting step of catecholamines? Why?

A

NO
Because this shit is NON-selective…i.e. there is no clinical scenario where you would want to decrease dopamine, NE AND E lol

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8
Q

What do you use to inhibit NE synthesis?

A
  1. Alpha-methyl-p-tyrosine
    -competitive inhibitor of tyrosine hydroxylase
  2. (alpha) methyldopa
    -inhibits L-aramatic amino acid decarboxylase
    Less dopamine
  3. Carbidopa
    Inhibits L-AAD in the periphery
    Less dopamine
  4. Tetraethylthiuram (disulfiram)
    -inhibits dopamine beta-hydroxylase
    Less NE
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9
Q

What is alpha-methyl-p-tyrosine?

A

Competitive inhibitor of tyrosine

LESS catecholamines

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10
Q

What is alphamethyldopa/carbidopa?

A

Blocks L-aromatic amino acid decarbaoxylase

Parkinson’s

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11
Q

What is reserpine?

A

Used to block VMAT so dopamine cant get into vesicle
Used for hypertension and SNAKE bite lol
Horrible drug because it is so powerful

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12
Q

What is Disulfiram?

A

Prevents NE FORMATION
Blocks dopamine hydroxylase
Used in alcohol dependence

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13
Q

How do you inhibit catecholamine release?

A
  1. Bretylium
    • causes NE release initially but THEN inhibits release by preventing Aps from reaching terminals
    • has been used to treat ventricular fibrillation
  2. Guanethidine
    • inhibits release of NE
    • powerful antihypertensive
    • leads to depletion of catecholamines and degradation of nerve endings
    • must be taken up into nerve terminal to have an effect
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14
Q

What is sympathomimetic response?

A

Increase Sympathetic

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15
Q

What is a sympatholytic response?

A

Decrease sympathetic

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16
Q

What are sympathomimetic amine agonists?

A
  1. Dopamine
  2. Dobutamine
  3. L-DOPA
17
Q

What is important to know about dopamine agonists?

A
  1. Inotropic agent

2. alpha and beta adrenoreceptor agonist

18
Q

What does inotropic mean?

A

Something that regulates the force and speed of muscle contraction

19
Q

What is Dobutamine?

A
  1. A beta receptor agonist
  2. produces inotropic effect
  3. used in congestive heart failure
20
Q

What are the two agonists used to treat PD?

A

L-DOPA
Bromocriptine
-selective D2 receptor agonist
-from lysergic acid

21
Q

What is Bromocriptine?

A

A D2 receptor agonist used to treat Parkinson’s

-LSD (acid) relative

22
Q

What are the properties of amphetamine/methamphetamine?

A

Lipid soluble (can penetrate into the brain)
Possess an alpha-methyl group that is RESISTANT to MAO
Promotes neurotransmitter release

23
Q

Why do neuroamines have a short half-life?

A

Due to the efficiency of MAO

24
Q

What are examples of inhibitors of catecholamine reuptake?

A
  1. Cocaine
    -block uptake-1 channels in presynaptic terminal
    Allows for more neuroepinephrine in the synapse
  2. Imipramine, a tricyclic
    Both are sympathomimetic
25
Q

What is Imipramine?

A

A tricyclic antidepressant

Blocks NE reuptake so amplifies NE response

26
Q

What inhibits catabolism (MAO inhibitors)?

A

Selegiline

- inhibits MAO-B at low doses
- delays breakdown of dopamine 
- USED IN PARKINSONS SO REMEMBER
- used as antidepressant because of effect on noradrenergic/serotnergic neurons
27
Q

What is Selegiline?

A

A Parkinson disease treatment
MAO-B inhibition
Delays breakdown of dopamine

28
Q

What are the drugs used for Parkinson’s disease?

A
  1. Seligiline (MAO-B inhibitor)
  2. Bromocriptine (D2 receptor agonist)
  3. L-DOPA
  4. Carbidopa

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