noradrenergic and serotonergic system Flashcards
peripheral nervous system
autonomic division: neuron to smooth muscle, cardiac muscle and glands.
somatic division: neuron to skeletal muscle
central nervous system
neuron to neuron
sites of CNS drug action
synthesis metabolism storage release reuptake degradation receptor ion conductance secondary messengers
CNS neurotransmitters
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
principles of CNS drug action
- selectivity for the targeted pathway:
- receptor subtype
- allosteric sites on receptor
- pre- and postsynaptic action
- partial/inverse agonist (activity dependent) - plasticity reveals adaptive changes in drug response
- pharmacokinetic: metabolism
- pharmacodynamic: cellular
monoamine neurotransmitters
NE, E, DA, 5-HT
Norepinephrine
Cell bodies: locus coeruleus, lateral tegmental area
Terminals: cerebral cortex, thalamus, cerebellum, brianstem nuclei, spinal cord, basal forebrain, hypothalamus
Epinephrine
Cell bodies: small, discrete nuclei in medulla.
Terminals: thalamus, brainstem, spinal cord
Dopamine (DA)
Cell bodies: substantia nigra pars compacta, ventral tegmental area, and arcuate nucleus
Terminals:
- SNpc - Striatum
- VTA - limbic forebrain, cerebral cortex
- AN - median eminence
Serotonin (5-HT)
Cell bodies: Raphe nuclei (median and dorsal), Pons and medulla
Terminals: cerebral cortex,
thalamus, cerebellum, brainstem
nuclei, spinal cord
important monoamines formed in the CNS
- NE –> MAO, COMT –> MHPG (MOPEG)
- DA –> MAO, COMT –> HVA
- 5HT –> MAO –> 5HIAA
CNS functions regulated by NE
- Arousal
- Mood
- Blood pressure control
CNS functions regulated by
5HT
- Sleep
- Mood
- Sexual function
- Appetite
serotonin receptors
- 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
Drugs acting on the noradrenergic neurons
Reserpine NRI and SNRI Tropolone Prazosin AMPT MAOI Yohimbine Clonidine Propranolol
Reserpine
inhibits VMAT and depletes NE stores
NRI and SNRI
antidepressants, inhibits the NE transporter (NET)
Tropolone
inhibits COMT
Prazosin
a1 antagonist
AMPT
inhibits tyrosine hydroxylase and NE synthesis
MAOI
antidepressants, inhibits MAO (monoamine oxidase)
yohimbine
a2 antagonist
clonidine
a2 agonist
propranolol
b antagonist
drugs acting on serotonergic neurons
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
