noradrenergic and serotonergic system

Question 1

peripheral nervous system

Answer 1

autonomic division: neuron to smooth muscle, cardiac muscle and glands.
somatic division: neuron to skeletal muscle

Question 2

central nervous system

Answer 2

neuron to neuron

Question 3

sites of CNS drug action

Answer 3

synthesis
metabolism 
storage 
release 
reuptake 
degradation
receptor 
ion conductance
secondary messengers

Question 4

CNS neurotransmitters

Answer 4

monoamines:
Catecholamines - DA, NE,E - GPCR
Indolamines - serotonin - GPCR

Acetylcholine - GPCR

Amino acids:
GABA and Glycine (inhibitory) - Ion channels
Glutamate and aspartate (excitatory) - ion channels

Question 5

principles of CNS drug action

Answer 5

1. selectivity for the targeted pathway:
   - receptor subtype
   - allosteric sites on receptor
   - pre- and postsynaptic action
   - partial/inverse agonist (activity dependent)
2. plasticity reveals adaptive changes in drug response
   - pharmacokinetic: metabolism
   - pharmacodynamic: cellular

Question 6

monoamine neurotransmitters

Answer 6

NE, E, DA, 5-HT

Question 7

Norepinephrine

Answer 7

Cell bodies: locus coeruleus, lateral tegmental area

Terminals: cerebral cortex, thalamus, cerebellum, brianstem nuclei, spinal cord, basal forebrain, hypothalamus

Question 8

Epinephrine

Answer 8

Cell bodies: small, discrete nuclei in medulla.

Terminals: thalamus, brainstem, spinal cord

Question 9

Dopamine (DA)

Answer 9

Cell bodies: substantia nigra pars compacta, ventral tegmental area, and arcuate nucleus

Terminals:

• SNpc - Striatum
• VTA - limbic forebrain, cerebral cortex
• AN - median eminence

Question 10

Serotonin (5-HT)

Answer 10

Cell bodies: Raphe nuclei (median and dorsal), Pons and medulla

Terminals: cerebral cortex,
thalamus, cerebellum, brainstem
nuclei, spinal cord

Question 11

important monoamines formed in the CNS

Answer 11

• NE –> MAO, COMT –> MHPG (MOPEG)
• DA –> MAO, COMT –> HVA
• 5HT –> MAO –> 5HIAA

Question 12

CNS functions regulated by NE

Answer 12

• Arousal
• Mood
• Blood pressure control

Question 13

CNS functions regulated by

5HT

Answer 13

• Sleep
• Mood
• Sexual function
• Appetite

Question 14

serotonin receptors

Answer 14

• 5-HT-1: GPCR - decrease cAMP - Inhibitory
• 5-HT-2: GPCR - increase IP3 and DAG - Excitatory
• 5-HT-3: Ligand gated Na+ and K+ channel - Depolarizing plasma membrane - excitatory
• 5-HT-4: GPCR - Increase cAMP - excitatory
• 5-HT-5: GPCR - decrease cAMP - inhibitory
• 5-HT-6: GPCR - Increase cAMP - excitatory
• 5-HT-7: GPCR - Increase cAMP - excitatory

Question 15

Drugs acting on the noradrenergic neurons

Answer 15

Reserpine 
NRI and SNRI
Tropolone 
Prazosin 
AMPT
MAOI
Yohimbine 
Clonidine 
Propranolol

Question 16

Reserpine

Answer 16

inhibits VMAT and depletes NE stores

Question 17

NRI and SNRI

Answer 17

antidepressants, inhibits the NE transporter (NET)

Question 18

Tropolone

Answer 18

inhibits COMT

Question 19

Prazosin

Answer 19

a1 antagonist

Question 20

AMPT

Answer 20

inhibits tyrosine hydroxylase and NE synthesis

Question 21

MAOI

Answer 21

antidepressants, inhibits MAO (monoamine oxidase)

Question 22

yohimbine

Answer 22

a2 antagonist

Question 23

clonidine

Answer 23

a2 agonist

Question 24

propranolol

Answer 24

b antagonist

Question 25

drugs acting on serotonergic neurons

Answer 25

Reserpine - inhibits VMAT and depletes serotonin
SSRI and SNRI - antidepressants, inhibit transport
many antipsychotics - 5-HT-2a inhibition
Odansetron - 5-HT-3 antagonist
PCPA - inhibit tryptophan hydrolase and serotonin synthesis
antimigraine triptans - 5-HT-1d agonists
MAOI - inhibits monoamine oxidase
Buspirone - partial agonist at 5-HT-1a