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Neuro Pharmacology > DA 5HT & Amino Acids > Flashcards

DA 5HT & Amino Acids Flashcards

1
Q

What is the pharmacology of DA?

A

CNS regulation of movement, attention, reward, behavior, and endocrine function.

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2
Q

What is involved in the synthesis and catabolism of DA?

A
  1. Tyrosine hydroxylase, Dopa Decaboxylase

2. VMAT, DAT, MAOb

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3
Q

What are the 4 main brain DA pathways?

A
  1. Nigrostriatal (SN –> Striatum)
  2. Mesolimbic (VTA –> NA, HP, AMY, etc.)
  3. Mesocortical (VTA –> PFc)
  4. Tuberoinfundibular.
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4
Q

Which DA receptors are coupled to Gs proteins and what do they do?

A

D1 & D5

1. Increase cAMP (typically postsynaptic)

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5
Q

Where are D1 and D5 receptors located?

A 
Substantia nigra
Striatum
Cortex
Limbic
Hypothalamus
Blood vessels
Kidneys
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6
Q

Which DA receptors are coupled to Gi proteins and what do they do?

A

D2, D3, D4-lik receptors

1. Decrease cAMP (presynaptic & postsynaptic)

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7
Q

Where are D2, D3, and D4 DA receptors located?

A 
Substantia nigra
Striatum
Cortex
Limbic
Pituitary
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8
Q

What uses do DA receptor agonists have?

A

Parkinson’s
ADHD
Hyperprolactinemia
Restless Leg Syndrome

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9
Q

What uses do DA receptor antagonists have?

A

Anti-emtics
Anti-psychotics
Movement disorders (Huntington’s, Tourettes’s, Dystonia’s)

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10
Q

Peripherally what roles does 5-hydroxytryptamine (5-HT) play?

A
  1. Storage granules in platelets (aggregation)
  2. Enteric NS (Peristalsis, nausea/vomiting)
  3. Blood vessels (microcirculation)
  4. Cardiac valves
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11
Q

Centrally what roles does 5-hydroxytryptamine (5-HT) play?

A
  1. Control of mood, appetite, sleep, nausea/vomiting, nociception.
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12
Q

What are clinical conditions that involve 5HT neurotransmission?

A
  1. Migraine
  2. Anxiety
  3. Schizophrenia
  4. Depression
  5. Nausea and vomiting
  6. Aggression and Impulsivity
  7. OCD
  8. Phobias
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13
Q

Where is 5HT formed?

A

Raphe Nucleus

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14
Q

What enzymes are involved in forming 5HT?

A
  1. Tryptophan Hydroxylase (Tryptophan –> 5-hydroxytryptophan)
  2. Dopa Decaboxylase (aromatic amino acid D)
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15
Q

What does MAO break 5HT down to?

A

5HIAA

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16
Q

What enzymes are involved in melatonin formation. What is it formed from and where?

A
  1. 5HT N-acetyltransferase
  2. 5-hydroxyindole-O-methyltransferase

From 5HT and in Pineal Gland.

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17
Q

Where are B1, B2, B3 located?

A

Raphe Magnus

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18
Q

Where is B4 located?

A

Raphe Obscurus

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19
Q

Where are B5, B8, B9 located?

A

Medial Raphe

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20
Q

Where is B6, B7 located?

A

Dorsal Raphe

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21
Q

Where are melatonin receptors located?

A

SCN, Anterior Pituitary, Periphery.

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22
Q

The 5HT1 receptor is coupled to what G protein?

A

GI –> Decreases cAMP.

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23
Q

The 5HT2 receptor is coupled to what G protein?

A

Gq –> Increase IP3/DAG

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24
Q

Other 5HT receptors (not 5HT1, 5HT2) are coupled to what G protein?

A

Gs –> Increase cAMP.

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25
Q

What is the Serotonergic Syndrome?

A
  1. Toxic, potentially fatal effects of combined drugs.

2. Wide range of central and peripheral adverse responses.

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26
Q

What are the symptoms of serotonergic syndrome?

A
  1. Diarrhea, Euphoria, drowsiness, sustained REM
  2. Overreaction of reflexes, rapid muscle contraction.
  3. Dizzy, high temp, shivering, seizures
  4. irregular heart beat, loss of consciousness, death.
27
Q

What are the predominant transmitters in the mammalian brain?

A

Glutamate and GABA

28
Q

What does glutamate cause?

A

Excitation.

29
Q

What does GABA cause?

A

Inhibition.

30
Q

Which drugs either enhance GABA receptor activity or Block Glutamate receptor activity?

A

Anxiolytic
Anti-convulsants
Anesthetics
Alcohol.

31
Q

What is the metabolic role of AA as NT?

A

NTs were previously viewed as products of “secondary” metabolism.

32
Q

What is the distribution role of AA as NT?

A

AANTs present throughout nerve and glial cells.

33
Q

What is the concentration role of AA as NT?

A

AA present in very high concentration in the CNS & uM conc. needed to elicit effects.

34
Q

What is the non-mammalian origins of AA as NT?

A

effects first seen in atypical synapses like crayfish NMJ.

35
Q

What does Transaminase do?

A

converts krebs cycle intermediates to glycine and aspartate.

36
Q

What does GABA tansaminase do?

A

Glutamate synthesis/ GABA catabolism –> Vigabatrin

37
Q

What does Glutamic acid decarboxylase (GAD) do?

A

Regulates GABA synthesis from glutamate

-Vit. B6 is a co-factor.

38
Q

What kind of transporters are VGAT & VGLT?

A

Vesicular transporters.

39
Q

What are examples of plasma membrane transporters?

A
  1. Nerve Terminals & Glial Cells
  2. GABA transporter (GAT)
  3. Glutamate Transporter (Excitatory AA transporter) (EAATs)
40
Q

Where are EAAT 1 Transporters located?

A

Astrocytes

41
Q

Where are EAAT 2 Transporters located?

A

Presynaptic, and Astrocytes

42
Q

Where are EAAT 3 and EAAT 4 Transporters located?

A

Postsynaptic.

43
Q

What is the prominent NT in renshaw cells of the ventral horn of the spinal cord?

44
Q

What type of receptor is located on Renshaw Cells?

A

Nicotinic cholinergic receptor.

45
Q

What kind of inhibition do renshaw cells mediate?

A

“Recurrent Inhibition”

46
Q

What kind of receptors are glycine receptors structurally and functionally similar to?

A

GABAa receptors (LGIC,Cl); VGLYT, GLYT.

47
Q

What is Strychnine?

A
  1. Proconvulsant – Glycine receptor antagonist.
48
Q

What is Glycine a Co-agonist for?

A

NMDA receptors - binds at glycine B site.

-Strychnine is not a antagonist for this site.

49
Q

What does GABA stand for?

A

Gamma Amino Butyric Acid

50
Q

Why is GABA able to interact with a wide variety of receptor subtypes?

A

It is a highly flexible molecule that assumes many different conformations.

51
Q

What kind of receptors are GABAa receptors and what do they elicit?

A

LGICs

Increase Cl influx ; IPSP

52
Q

What is muscimol?

A

A selective GABAa agonist isolated from amanita muscaria.

53
Q

What is Bicuculine?

A

A competitive antagonist (Proconvulsive)

54
Q

What is Picrotoxin?

A

A Non-competitive Antagonists. (Un surmountable)

55
Q

What are the 5 important domains of the GABAa receptor?

A 
Cl- Channel
GABA recognition site
Benzodiazepine (BZ) binding site
Barbiturate/ Alcohol binding site
Neurosteroid/volatile anesthetic binding site.
56
Q

What do allosteric potentiating ligands do to GABA DRC?

A

Shift to the left.

57
Q

What are characteristics of the GABAb receptor?

A
  1. Metabotrophic; coupled to Gi
  2. Decrease cAMP; Close Ca2+ channels
  3. Similar to alpha 2 and muscarinic 2 receptors
  4. High conc. of GABAb in SC
  5. Decrease presynaptic NT release
58
Q

What is Baclofen?

A

A selective GABAb Agonist. (Muscle Relaxant)

59
Q

What are the 3 Ionotrophic Glutamate Receptors?

A
  1. Kainic Acid receptor
  2. AMPA receptor
  3. NMDA receptor
60
Q

What are Kainic acid receptors permeable to?

61
Q

What are AMPA receptors permeable to?

62
Q

What are NMDA receptors permeable to?

63
Q

What does activation of NMDA receptors require?

A

Both Glutamate and Glycine (act as co-agonists)

Neuro Pharmacology (9 decks)

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