CNS Neuropharmacology Flashcards
Acetyl-CoA + Choline → ACh + CoA
What is the enzyme involved in this process?
What is the Rate Limiting Step?
Choline Acetyl Transferase (CAT).
Choline uptake is the RDS.
What G_proteins fo the following subtypes of Muscarinic Receptors stimulate?
M1-M3 → ?
M2-M4 → ?
Muscarinic Receptors:
M1-M3 (Gq → stimulate PLC activity)
M2-M4 (Gi/o → inhibit AC activity)
Nicotinic Receptors, N_N, open receptor gated __?__ channel.
cation channel
Hows does ACh get terminated?
Enzymatic degradation catalyzed by acetylcholinesterase (AChE) in synapse
Where is ACh produced and distributed?
Produced in brainstem and basal forebrain, then project widely throughout cerebral cortex and hippocampus
What are the NTs that are considered Monoamines?
Monoamine (DA-NE-5HT)
What are the Catecholamines NTs?
Catecholamines: Dopamine, Norepinephrine
What are the steps in the the synthesis of DA and NE?
Tyrosine → (Tyrosine Hydroxylase = rate limiting step) → L-Dopa → (Dopa Decarboxylase) → Dopamine → (DBH) → Norepinephrine
What G-protein do the Dopamine receptors stimulate?
D1 → ?
D2 → ?
D1 (Gs → stimulate AC activity)
D2 (Gi/o → inhibit AC activity)
What G-protein do the Norepinephrine receptors stimulate?
- a1 adrenergic → ?
- a2 adrenergic → ?
- B1 adrenergic → ?
- B2 adrenergic → ?
- 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)
Where is the location of Dopamine?
Dopamine: Substantia Nigra, Ventral Tegmental Area
Where is the location of Norepinephrine ?
Norepinephrine: cell bodies in pons and brainstem (locus ceruleus, A1, A2, A5, A7) → project to all levels of brain
What is the function of DA?
Dopamine: initiate voluntary movement, reward-related behaviors, cognitive control of behavior
What is the function of NE?
Norepinephrine: arousal, attention, sleep-wake cycle, fear response/anxiety/mood/emotion, afferent pain signals.
What is the function of Indoleamine NTs?
What is an example of a Indoleamine NTs?
sleep, arousal, attention, processing of sensory info, emotion, mood, pain, eating/drinking.
Serotonin
How are Indoleamine NTs (serotonin) synthesized?
Tryptophan → (Tryptophan hydroxylase = rate limiting step) → 5-OH-tryptophan → (AAA Dec) → 5-HT
What is the enzyme (and RDS) involved in the synthesis of Indoleamine NTs (serotonin)?
Tryptophan hydroxylase
What G-protein do the 5HT receptors stimulate?
- 5HT-1A, 1B, 1D → ?
- 5HT-2A, 2B, 2C → ?
- 5HT3 → ?
- 5HT4 → ?
- 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)
Where are 5HT NTs located?
Cell bodies in raphe regions of pons/upper brainstem → project to all levels of brain
How are 5HT NTs stored?
Storage in vesicles via vesicular monoamine transporter (VMAT)
Packaged and protected from degradation via intraneuronal monoamine oxidase (MAO)
How are 5HT NTs terminated?
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)
Name a amino acid NT?
GABA-Glu
GABA (hierarchical systems) - major _______ neurotransmitter in CNS
inhibitory
How is GABA synthesized?
Precursor = Glutamate
Glutamate → GABA via GAD (glutamic acid decarboxylase)
How is GABA terminated?
GABA transporter allows reuptake into presynaptic nerve terminal and surrounding glial cells
What are the MOA of
GABA-A
GABA-B
- 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
Where is GABA located?
High concentration in brain and spinal cord
Absent in peripheral tissue
What is the precursor to GABA?
Glutamate
What are the 3 GABA drugs we learned about?
- Benzodiazepines
- Tiagabine
- Vigabatrin
What is the MOA of Benzodiazepines?
Benzodiazepines: bind GABA-A receptor, increase GABA inhibitory action.
What is the MOA of Tiagabine?
inhibit reuptake of GABA
What is the MOA of Vigabatrin?
inhibit degradation by GABA-transaminase (GABA-T)
What GABA drugs is used to Treat seizures caused by depressed GABA activity and anxiety caused by excessive amygdala activity/depressed GABA activity?
Benzodiazepines
What NT is the major excitatory synaptic transmission in CNS and trigger neuroplasticity?
Glutamate
How is Glutamate synthesized?
Glutamine → glutamate via Glutaminase in nerve endings, stored in synaptic vesicles.
Dependent on interaction between nerve terminals and glial cells
How is Glutamate terminated?
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
What are the 2 ionotropic receptors for glutamate?
- NMDA (Ca2+ influx)
- AMPA (Na+ and Ca2+ influx)
What are the metabotropic receptors for glutamate?
- 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)
Where is Glutamate located?
All neurons in CNS - highest in hippocampus, cortex, lateral septum, striatum, and cerebellum
Hierarchical Systems: ?
Hierarchical Systems:
Clearly delineated pathways directly involved in motor control and sensory perception
Large myelinated neurons with rapid conduction velocity
___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.
- Relay; Excitatory → NT = glutamate.
2. Local; Inhibitory → NT = GABA
Can diffuse systems convey topographically specific information?
NO!!!
