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DA 5HT & Amino Acids Flashcards

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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
What is the Serotonergic Syndrome?
1. Toxic, potentially fatal effects of combined drugs. | 2. Wide range of central and peripheral adverse responses.
26
What are the symptoms of serotonergic syndrome?
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
What are the predominant transmitters in the mammalian brain?
Glutamate and GABA
28
What does glutamate cause?
Excitation.
29
What does GABA cause?
Inhibition.
30
Which drugs either enhance GABA receptor activity or Block Glutamate receptor activity?
Anxiolytic Anti-convulsants Anesthetics Alcohol.
31
What is the metabolic role of AA as NT?
NTs were previously viewed as products of "secondary" metabolism.
32
What is the distribution role of AA as NT?
AANTs present throughout nerve and glial cells.
33
What is the concentration role of AA as NT?
AA present in very high concentration in the CNS & uM conc. needed to elicit effects.
34
What is the non-mammalian origins of AA as NT?
effects first seen in atypical synapses like crayfish NMJ.
35
What does Transaminase do?
converts krebs cycle intermediates to glycine and aspartate.
36
What does GABA tansaminase do?
Glutamate synthesis/ GABA catabolism --> Vigabatrin
37
What does Glutamic acid decarboxylase (GAD) do?
Regulates GABA synthesis from glutamate -Vit. B6 is a co-factor.
38
What kind of transporters are VGAT & VGLT?
Vesicular transporters.
39
What are examples of plasma membrane transporters?
1. Nerve Terminals & Glial Cells 2. GABA transporter (GAT) 3. Glutamate Transporter (Excitatory AA transporter) (EAATs)
40
Where are EAAT 1 Transporters located?
Astrocytes
41
Where are EAAT 2 Transporters located?
Presynaptic, and Astrocytes
42
Where are EAAT 3 and EAAT 4 Transporters located?
Postsynaptic.
43
What is the prominent NT in renshaw cells of the ventral horn of the spinal cord?
Glycine
44
What type of receptor is located on Renshaw Cells?
Nicotinic cholinergic receptor.
45
What kind of inhibition do renshaw cells mediate?
"Recurrent Inhibition"
46
What kind of receptors are glycine receptors structurally and functionally similar to?
GABAa receptors (LGIC,Cl); VGLYT, GLYT.
47
What is Strychnine?
1. Proconvulsant -- Glycine receptor antagonist.
48
What is Glycine a Co-agonist for?
NMDA receptors - binds at glycine B site. | -Strychnine is not a antagonist for this site.
49
What does GABA stand for?
Gamma Amino Butyric Acid
50
Why is GABA able to interact with a wide variety of receptor subtypes?
It is a highly flexible molecule that assumes many different conformations.
51
What kind of receptors are GABAa receptors and what do they elicit?
LGICs | Increase Cl influx ; IPSP
52
What is muscimol?
A selective GABAa agonist isolated from amanita muscaria.
53
What is Bicuculine?
A competitive antagonist (Proconvulsive)
54
What is Picrotoxin?
A Non-competitive Antagonists. (Un surmountable)
55
What are the 5 important domains of the GABAa receptor?
``` Cl- Channel GABA recognition site Benzodiazepine (BZ) binding site Barbiturate/ Alcohol binding site Neurosteroid/volatile anesthetic binding site. ```
56
What do allosteric potentiating ligands do to GABA DRC?
Shift to the left.
57
What are characteristics of the GABAb receptor?
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
What is Baclofen?
A selective GABAb Agonist. (Muscle Relaxant)
59
What are the 3 Ionotrophic Glutamate Receptors?
1. Kainic Acid receptor 2. AMPA receptor 3. NMDA receptor
60
What are Kainic acid receptors permeable to?
Na+
61
What are AMPA receptors permeable to?
Na+
62
What are NMDA receptors permeable to?
Ca2+
63
What does activation of NMDA receptors require?
Both Glutamate and Glycine (act as co-agonists)

Neuro Pharmacology (9 decks)

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