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CNS > Neurochemistry 3 > Flashcards

Neurochemistry 3 Flashcards

1
Q

What are biogenic amines implicated in

A

e.g. movement, reward, addiction, depression, sleep

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2
Q

Name 5 biogenic amines

A

Dopamine (catecholamine)

Norepinephrine (catecholamine)

Epinephrine (catecholamine)

Indoleamine - serotonin (5-HT)

Imidazoleamine - histamine

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3
Q

Name 3 catecholamines

A

Dopamine

Norepinephrine

Epinephrine

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4
Q

Synonym for serotonin

Where is it present

What is it synthesised from

What are high AND low serotonin levels associated with

what drugs use serotonergic neurons as their target

A

5-HT - 5-hydroxytryptamine

Present in serum (initially thought to increase vascular tone)

Synthesised from tryptophan

High serotonin - happiness, sleep, appetite, sex drive

low serotonin - depression & anxiety

Certain antipsychotic drugs in treatment of depression and anxiety act specifically on serotonergic neurons

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5
Q

Rate limiting step in synthesis of serotonin

A

Tryptophan hydroxylase

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6
Q

Describe the serotonin receptors

A

Most are GPCRs linked to G proteins that modulate cAMP production and phospholipase C activity

5-HT3 receptor is a ligand gated Na+ channel

(5-HT 1-7)

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7
Q

2 classes of serotonin reuptake inhibitors

A

TCAs - tricyclic anti-depressants - inhibit reuptake of serotonin and norepinephrine

SSRIs - selective serotonin reuptake inhibitors - e.g. fluoxetine (prozac)

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8
Q

What does tyrosine hydroxylase do

Where is it found

How is its expression controlled

A

Controls rate limiting step

Only found in symapthetic neurons and adrenal chromaffin cells

Diagnostic of a chatecholaminergic cell

Its expression in a cell is controlled by Nerve Growth Factor and other factors controlling growth and differentiation of sympathetic neurons

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9
Q

What structures have a common origin in early embryonic development

A

SNS and adrenal gland

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10
Q

Synthesis of catecholamines

A
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11
Q

How are NTs (catecholamines & indoleamines) taken into and stored in vesicles

A

Vesicular Monoamine Transporter (VMAT)

Can transport catecholamines and indoleamines

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12
Q

What is VMAT inhibited by

A

Reserpine

Used before to treat hypertension and psychosis

Mediates its actions by depleting dopamine in nerve terminal - inhibits all catecholamine so not specific

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13
Q

What do vesicles in adrenergic neurons and chromaffin cells contain

A

Dopamine B-hydroxylase (DBH)

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14
Q

Name of vesicles in adrenal chromaffin cells

A

Chromaffin granules

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15
Q

Where is norepinephrine synthesised

A

Within the synaptic vesicles - THE ONLY 1

Hence, as adrenal chromaffin cells = chromaffin granules, epinephrine is produced in the chromaffin granules

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16
Q

What type are catecholamine receptors

A

All are coupled to G proteins

17
Q

What receptors does dopamine bind to

A

D1-5

18
Q

What are the D1-like receptors

MOA

A

D1 & D5

Activate adenylate cyclase - increases cAMP

19
Q

What are the D2-like receptors

MOA

A

Inhibit adenylate cyclase - decreases cAMP

20
Q

3 mechanisms of inactivation of biogenic amines

A
  1. reuptake via dopamine transporter - Na+ dependent transport protein which is INHIBITED BY cocaine & amphetamine
  2. Enzymatic degradation
  3. Diffusion away from synaptic cleft
21
Q

MOA of cocaine and amphetamine

Inhibit reuptake via dopamine transporter (Na+ dependent)

A
22
Q

What is the enzymatic inactivation of dopamine

A
23
Q

Function of monamine oxidase

What is it associated with

What does it work with

A

MAO enzymes deaminate catecholamines → inactive derivatives

Associated with outer mito. membrane

Works with AD - aldehyde dehydrogenase

24
Q

MOA of COMT - catechol-O-methyltransferase

Where is it found

A

Transfers methyl groups to hydroxyl group of catechols

Cytosolic

25
Q

What diseases is the dopamine system associated with

A

Parkinsons

Attention deficit hyperactivity disorder

Tourette syndrome

Schizophrenia

Bipolar disorder

Addiction

26
Q

Pathophysiology of Parkinsons

A

Insufficient dopamine in the nigrostriatal pathway

Dopaminergic neurons project from the substantia nigra to the striatum

27
Q

Neural projections in motor control

A
28
Q

What happens to our dopamine producing cells as we age

How does this change in Parkinsons

A

Form neuromelanin

29
Q

What are the familial mitochondrial alterations in Park genes

A

Mitochondrial dysfunction - Parkin (Park2), DJ-1 (Park7), PINK (Park6)

30
Q

Familial alterations in Park genes - UPS

A

Defects in ubiquitin-proteasome system (UPS)

Alpha-synuclein (Park1)

Parkin

DJ-1

31
Q

Sporadic causes of Parkinsons

A

Environmental toxins - MPTP, rotenone

Oxidation of dopamine - 6-hydroxydopamine

32
Q

What does the biochem of parkinsons cause in the cell

A

Oxidative stress

Protein aggregation

33
Q

What is the main component of lewy bodies

How do they change with Parkinsons

A

Synupian

34
Q

Sites of action of common treatments for Parkinsons

A
35
Q

Levodopa

A

Increases dopamine levels

36
Q

Selegeline

A

Inhibits MAO-B

37
Q

Amantidine

A

Stimulates release of DA

Inhibits reuptake

38
Q

DA Agonists

A

Bind to DA receptors

39
Q

COMT inhibitors

Block degradation of DA and L-DOPA

A

CNS (36 decks)

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