serotonin , 5-Hydroxytryptamine, its 90% present in

1. Hawler Medical University
College of Medicine
Department of Pharmacology
SEROTONIN
Pharmacist:
Asma A. Abdulqader

2. INTRODUCTION
Serotonin /ˌsɛrəˈtoʊnɨn/ or
5-hydroxytryptamine (5-HT) is a monoamine
neurotransmitter. Biochemically derived
from tryptophan.
Serotonin is primarily found in the gastrointestinal
tract (GI tract), blood platelets, and the central
nervous system (CNS).
It is popularly thought to be a contributor to
feelings of well-being and happiness

3. Biosynthesis and metabolism of 5-
hydroxytryptamine

4. Serotonin pathways in the Brain
Serotonin pathways that are located in the
brainstem area “the Raphe nuclei” these neurons
control muscle activity, 5-HT receptors trigger
vomiting.
The serotonin neurons in frontal cortex, regulate
cognition and memory.
The serotonin neurons in the hippocampus
regulate memory.
The serotonin neurons in the other limbic areas
regulate mood. ( basal ganglia and cerebral
cortex). SSRI’s work in this pathway.

6. Actions and functions of serotonin
• Important actions:
Increased GI motility (direct excitation of
smooth muscle and indirect action via enteric
neurons.
Contraction of the other smooth muscles
(bronchi and uterus).
Mixture of vascular constriction (direct via
sympathetic innervation) and dilation
(endothelium dependant.

7. Continue…
Platelet aggregation
Stimulation of peripheral nociceptive nerve
endings
Excitation/inhibition of CNS neurons.

8. Continue…
• Postulated physiological and
pathophysiological roles include:
In periphery: peristalsis, vomiting, platelet
aggregation and haemostasis, inflammatory
mediator, sensitization of nociceptors and
microvascular control.
In CNS, control of appetite, sleep, mood,
hallucinations, steriotyped behavior, pain
perception and vomiting.

9. Clinical conditions associated with 5-
hydroxytryptamine function include migraine,
carcinoid syndrome, mood disorders and
anxiety.

10. Receptors
Classical signal transductionType of receptorSubtypeFamily
Inhibit AC, reduce cAMP, inhibit
PKA
Gi/G0- protein
coupled
1A,1B,1D,
1E,1F5-HT1
Increase IP3, increase intracellular
Ca ion, activate PKC
Gq- Protien
coupled
2A,2B,2C
5-HT2
Membrane depolarizationLigand-gated Na
and K ion ch.
5-HT3
Activate AC, increase cAMP,
activate PKA
Gs-protein coupled5-HT4
Activate AC, increase cAMP,
activate PKA
Gs- protein
coupled
5A,5B5-HT5
Activate AC, increase cAMP,
activate PKA
Gs- protein
coupled
5-HT6
5-HT7

11. Drugs acting on 5-HT receptors
antagonistagonistfunctionlocationreceptor
Ergotamine(P
A),
methiothepin
Buspirone(
PA), triptans
Neuronal
inhibition,
sleep,
behavior,
feeding,
anxiety
CNS, vascular
smooth muscle
5-HT1
Ketanserin,
ciproheptadin
e, pizotifen,
ketotifen
LSDNeuronal
excitation,
smooth
muscle
contraction,
platelet
aggrigation
CNS, PNS,
smooth muscle,
platelets
5-HT2

12. Ondansetron,
granisetron,
palonosetron
-------Neuronal
excitation(no
ciceptive,aut
onomic
neurons,eme
sis, anxiety
PNS, CNS5-HT3
Metoclopromi
de, cisapride
Neuronal
excitation, GI
motility
PNS (GIT) ,
CNS
5-HT4
----------Modulation
of behavior?
PNS, CNS5-HT5
--------Learning and
memory??
CNS,
Leukocytes
5-HT6
LSDThermoregula
tion?
CNS, GIT,
Blood vessels
5-HT7

13. Clinical utility
Sumatriptan, ergotaminemigraine
buspironeanxiety
ondansetronControl of vomiting
cisaprideGastric stasis , GERD
Methisergide, cyproheptadines
Citalopram, flouxetine
Carcinoid tumor
depression

14. Pathogenesis of migriane

15. Carcinoid syndrome
• Rare disorder associated with malignant tumors
of enterochromaffin cells, which usually arise
from small intestine and metastasize to the liver.
• Tumors secrete a variety of mediators, 5-HT is the
most important.
• the release of these substances into the
bloodstream leads to symptoms, include flushing,
diarrhea, bronchoconstriction and hypotension
that causes dizziness and fainting.
• 5-HT2 antagonists, such as cyproheptadine given
for controlling some symptoms.

16. Role of serotonin in emesis

17. Selective serotonin reuptake
inhibitors
 SSRI are currently first choice of medication
for depression.
Work by blocking reabsorption of serotonin by
nerve cells in the brain. Leaving more
serotonin available in the brain.
This increase will enhance sending of nerve
impulses and improves mood.
They only affect serotonin and not others NTs.

18. SSRI’s

19. Indications of SSRI’s
Depression: all SSRI except fluvoxamine.
Anxiety disorders like social anxiety: safer
than MAOI and BDZ.
Panic disorders: paroxetine and sertraline.
Obsessive-compulsive disorder (OCD):
fluoxetine, sertraline, and fluvoxamine.
Eating disorders: Fluoxetine.
Premenstrual dysphoric disorder (PMDD):
sertraline, paroxetine and fluoxetine.

20. Common side effects of SSRI
 Nausea
 Sexual dysfunction
 Dry mouth
 Headache
 Diarrhea
 Nervousness
 Rash
 Weight gain
 Insomnia
 Agitation, restlessness

21. Serotonin syndrome
Rare life-threatening side effect of SSRI
characterized by dangerously high levels of
serotonin in the brain.
Can occur when SSRI taken together with
MAOIs

22. Serotonin syndrome
Can occur when SRRI are taken with other
medications:
Pain relief medications such as tramadol.
Migraine medication such as sumatriptan.
Supplemnets that affect serotonin levels,
such as St. Johns Wort.

23. Symptoms:
 Confusion
 Anxiety
 Extreme agitation
 Fluctuation in blood pressure
 Increased heart rate
 Nausea and vomiting
 Fever
 Seizure
 Flu like symptoms
 Lethargy
 Coma

24. Drugs used to treat serotonin
syndrome
Non-specific blocking agents:
methysergide, cyproheptadine.
Beta –adrenoceptor blockers:
propranolol, pindolol.
benzodiazepines: lorazepam, diazepam
Neuroleptics: chlorpromazine,
haloperidol