Serotonin Flashcards
____________ are a group of NTs/hormones that share a common single AMINE functional group.
monoamines
90% of the 5HT in your body is found in the ______.
gut
5-HT is a major NT in the _________________ and is released by ______________ cells.
enteric nervous system; enterochromaffin
5HT stimulates ________ and secretion into the intestines.
peristalsis
5HT is massively released in response to chemical, physical, and pathological stimuli and can activate __________ __________ to signal the brain in generation of nausea & act at the ________ ___________ (chemoreceptor trigger zone).
vagal afferents; area postrema
What is the area postrema?
chemoreceptor trigger zone
________ _______________ is transported into the brain where it is converted to 5HT by _______ _____________.
dietary L-tryptophan; tryptophan hydroxylase
What is the rate limiting enzyme in the production of 5HT?
tryptophan hydroxylase
5HT is deaminated by ____________ ___________ to _______________ ____________ in the cytoplasm of _____________ neurons.
monoamine oxidase; 5-hydroxyindoleacetic acid; serotonergic
In contrast to the catecholamines, 5HT breakdown occurs only through ________.
MAO
Describe the enzymes and pathway of 5HT synthesis and catabolism
L-tryptophan –tryptophan hydroxylase–> 5-HTP –decarboxylase–> 5HT –MAO–> 5-HIAA
REVIEW slide 5 diagram
slide 5
_________________ (__________) is used in animals to rapidly deplete 5HT.
para-chlorophenylalanine (PCPA)
TRUE or FALSE: PCPA is a reversible antagonist of tryptophan hydroxylase.
FALSE: irreversible inhibitor
PCPA is an irreversible inhibitor of ________________.
tryptophan hydroxylase
1-2 doses of PCPA depletes 5HT by up to _____% for up to ___ weeks.
90; 2
______________ also depletes 5HT by inhibiting VMAT.
reserpine
Tryptophan can be depleted in humans by administering an amino acid mix devoid of ____________.
tryptophan
How does an amino acid mix devoid of tryptophan deplete tryptophan in humans?
- boost of AAs triggers protein synthesis in liver, depleting previous supply of tryptophan
- neutral AAs compete for BBB transporters
Which substances can be used for tryptophan/5HT depletion? What is the mechanism?
- PCPA - irreversible inhibitor of tryptophan hydroxylase
- reserpine - inhibit VMAT
- AA mix w/o tryptophan - protein synthesis depletes previous supply of tryptophan
TRUE or FALSE: tryptophan-containing mixture will lead to a more sad mood, in comparison to a tryptophan-free mixture
FALSE: no tryptophan = more sad
review sllide 8 diagram
slide 8
What are some 5-HT releasers? What are they typically used for?
- fenfluramine - weight loss in obesity
- para-chloroamphetamine - experimental amphetamine analogue
- 3,4-methylenendioxymethamphetamine (MDMA) - psychoactive recreational drug (Ecstasy)
TRUE or FALSE: fenfluramine is a 5HT depleter
FALSE: 5HT releaser
Which 2 NTs are directly opposed in regulating appetite?
dopamine and 5HT
How does dopamine regulate appetite?
- stimulate appetite
- released in response to food stimuli (smell)
How does 5HT regulate appetite?
- decrease appetite
- released in response to eating
- inhibits dopamine release
___________________ suppresses appetite through effects on catecholamines (psychostimulant like amphetamine)
phentermine
__________ came into use in the 1990s as an off-label prescription for obesity.
Fen-Phen (fenfluramine-phentermine)
Why is phentermine used with fenfluramine in treating obesity?
co-treatmen avoided DROWSINESS and ADVERSE MOOD effects associated with fenfluramine
review graph on slide 11
slide 11
TRUE or FALSE: Fen-Phen is FDA approved for weight loss
FALSE: never FDA approved
What severe adverse consequences are linked with long-term Fen-Phen use?
- heart valve abnormalities
- primary pulmonary hypertension - increased BP between heart and lungs (often fatal)
Both fenfluramine and dexfenfluramine removed from clinical used in late __________.
1997
What class of transporters is responsible for inactivation of 5HT signalling by reuptake?
5HT transporters (SERT)
SERT is similar to _____ and ________.
DAT; NAT
TRUE or FALSE: many drugs jave effects at all 3 transporters (SERT, DAT, NET)
TRUE
SERT also found in __________, ___________, and _____________.
lungs, placenta, platelets
SERT pumps systemic 5HT into ___________.
platelets
TRUE or FALSE: SERT functions in clotting cascades as a vasodilator.
FALSE: vasoconstrictor
TRUE or FALSE: SERT is a popular drug target
TRUE
Which drug classes target SERT? Which ones are selective/non-selective?
- TCA antidepressants (non-selective for SERT, NET)
- SSRI antidepressants (selective for SERT)
- SNRI antidepressants (non-selective for SERT, NET)
- SNDRI antidepressants (SERT~NET>DAT)
- psychoactive drugs (non-selective for SERT, NET, DAT)
What class of drugs does imipramine belong to?
TCA antidepressants
What class of drugs does fluoxetine belong to?
SSRI antidepressants
What class of drugs does venlafaxine belong to?
SNRI antidepressants
What class of drugs do cocaine, amphetamines, MDMA belong to?
psychoactive drugs
