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NS_BTRAN > CNS Neuropharmacology > Flashcards

CNS Neuropharmacology Flashcards

1
Q

Acetyl-CoA + Choline → ACh + CoA

What is the enzyme involved in this process?

What is the Rate Limiting Step?

A

Choline Acetyl Transferase (CAT).

Choline uptake is the RDS.

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2
Q

What G_proteins fo the following subtypes of Muscarinic Receptors stimulate?

M1-M3 → ?

M2-M4 → ?

A

Muscarinic Receptors:
M1-M3 (Gq → stimulate PLC activity)
M2-M4 (Gi/o → inhibit AC activity)

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3
Q

Nicotinic Receptors, N_N, open receptor gated __?__ channel.

A

cation channel

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4
Q

Hows does ACh get terminated?

A

Enzymatic degradation catalyzed by acetylcholinesterase (AChE) in synapse

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5
Q

Where is ACh produced and distributed?

A

Produced in brainstem and basal forebrain, then project widely throughout cerebral cortex and hippocampus

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6
Q

What are the NTs that are considered Monoamines?

A

Monoamine (DA-NE-5HT)

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7
Q

What are the Catecholamines NTs?

A

Catecholamines: Dopamine, Norepinephrine

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8
Q

What are the steps in the the synthesis of DA and NE?

A

Tyrosine → (Tyrosine Hydroxylase = rate limiting step) → L-Dopa → (Dopa Decarboxylase) → Dopamine → (DBH) → Norepinephrine

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9
Q

What G-protein do the Dopamine receptors stimulate?

D1 → ?
D2 → ?

A

D1 (Gs → stimulate AC activity)

D2 (Gi/o → inhibit AC activity)

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10
Q

What G-protein do the Norepinephrine receptors stimulate?

  • a1 adrenergic → ?
  • a2 adrenergic → ?
  • B1 adrenergic → ?
  • B2 adrenergic → ?
A
  • a1 adrenergic (Gq → stimulate phospholipase C)
  • a2 adrenergic (Gi/o → inhibit AC activity, K+ channel opening)
  • B1 adrenergic (Gs → stimulate AC activity)
  • B2 adrenergic (Gs → stimulate AC activity)
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11
Q

Where is the location of Dopamine?

A

Dopamine: Substantia Nigra, Ventral Tegmental Area

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12
Q

Where is the location of Norepinephrine ?

A

Norepinephrine: cell bodies in pons and brainstem (locus ceruleus, A1, A2, A5, A7) → project to all levels of brain

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13
Q

What is the function of DA?

A

Dopamine: initiate voluntary movement, reward-related behaviors, cognitive control of behavior

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14
Q

What is the function of NE?

A

Norepinephrine: arousal, attention, sleep-wake cycle, fear response/anxiety/mood/emotion, afferent pain signals.

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15
Q

What is the function of Indoleamine NTs?

What is an example of a Indoleamine NTs?

A

sleep, arousal, attention, processing of sensory info, emotion, mood, pain, eating/drinking.

Serotonin

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16
Q

How are Indoleamine NTs (serotonin) synthesized?

A

Tryptophan → (Tryptophan hydroxylase = rate limiting step) → 5-OH-tryptophan → (AAA Dec) → 5-HT

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17
Q

What is the enzyme (and RDS) involved in the synthesis of Indoleamine NTs (serotonin)?

A

Tryptophan hydroxylase

18
Q

What G-protein do the 5HT receptors stimulate?

  • 5HT-1A, 1B, 1D → ?
  • 5HT-2A, 2B, 2C → ?
  • 5HT3 → ?
  • 5HT4 → ?
A
  • 5HT-1A, 1B, 1D (Gi/o → inhibit AC activity, open K+ channel)
  • 5HT-2A, 2B, 2C (Gq → stimulate PLC activity, close Ca2+ channel)
  • 5HT3 (Ligand-gated cation channel, excitatory)
  • 5HT4 (Gs → stimulate AC activity)
19
Q

Where are 5HT NTs located?

A

Cell bodies in raphe regions of pons/upper brainstem → project to all levels of brain

20
Q

How are 5HT NTs stored?

A

Storage in vesicles via vesicular monoamine transporter (VMAT)
Packaged and protected from degradation via intraneuronal monoamine oxidase (MAO)

21
Q

How are 5HT NTs terminated?

A

Primarily by presynaptic membrane transport back into nerve terminal (Reuptake) → once in cytosol, inactivated by MAO or transported into vesicles by VMAT)
Specific transporters for each monoamine (DAT, NET, SERT)

22
Q

Name a amino acid NT?

A

GABA-Glu

23
Q

GABA (hierarchical systems) - major _______ neurotransmitter in CNS

A

inhibitory

24
Q

How is GABA synthesized?

A

Precursor = Glutamate

Glutamate → GABA via GAD (glutamic acid decarboxylase)

25
Q

How is GABA terminated?

A

GABA transporter allows reuptake into presynaptic nerve terminal and surrounding glial cells

26
Q

What are the MOA of

GABA-A

GABA-B

A
  • GABA-A: opens ligand-gated Cl-channel → decrease neuronal excitability (IPSP)
    Postsynaptic only
  • GABA-B: Gi/o → inhibit AC, decrease Ca2+ conductance, open K+ channel. Pre and postsynaptic
27
Q

Where is GABA located?

A

High concentration in brain and spinal cord

Absent in peripheral tissue

28
Q

What is the precursor to GABA?

A

Glutamate

29
Q

What are the 3 GABA drugs we learned about?

A
  • Benzodiazepines
  • Tiagabine
  • Vigabatrin
30
Q

What is the MOA of Benzodiazepines?

A

Benzodiazepines: bind GABA-A receptor, increase GABA inhibitory action.

31
Q

What is the MOA of Tiagabine?

A

inhibit reuptake of GABA

32
Q

What is the MOA of Vigabatrin?

A

inhibit degradation by GABA-transaminase (GABA-T)

33
Q

What GABA drugs is used to Treat seizures caused by depressed GABA activity and anxiety caused by excessive amygdala activity/depressed GABA activity?

A

Benzodiazepines

34
Q

What NT is the major excitatory synaptic transmission in CNS and trigger neuroplasticity?

A

Glutamate

35
Q

How is Glutamate synthesized?

A

Glutamine → glutamate via Glutaminase in nerve endings, stored in synaptic vesicles.

Dependent on interaction between nerve terminals and glial cells

36
Q

How is Glutamate terminated?

A

Reuptake of glutamate into neuron via Neuronal Glutamate Transporter.

Reuptake of glutamate into glial cell via Glial Cell Transporter → converted to glutamine by Glutamine Synthase → taken up into neuron again and converted back to glutamate

37
Q

What are the 2 ionotropic receptors for glutamate?

A
  • NMDA (Ca2+ influx)

- AMPA (Na+ and Ca2+ influx)

38
Q

What are the metabotropic receptors for glutamate?

A
  • R1-R5 (Gq → increase PLC activity)
  • R2-R3 (Gi/o → decreased AC activity, inhibit VSCC, activate K+ channels)
  • R4-R6-R7-R8 (Gi/o → decreased AC activity, inhibit VSCC)
39
Q

Where is Glutamate located?

A

All neurons in CNS - highest in hippocampus, cortex, lateral septum, striatum, and cerebellum

40
Q

Hierarchical Systems: ?

A

Hierarchical Systems:
Clearly delineated pathways directly involved in motor control and sensory perception

Large myelinated neurons with rapid conduction velocity

41
Q

___1___ neurons: in pathways that transmit signals over long distances, feed forward.

___2___ circuit interneurons: synapse on relay neuron cell body or on axon in spinal cord.

A
  1. Relay; Excitatory → NT = glutamate.

2. Local; Inhibitory → NT = GABA

42
Q

Can diffuse systems convey topographically specific information?

A

NO!!!

NS_BTRAN (21 decks)

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