This document presents information on serotonin (5-HT) from its biosynthesis and pathways in the brain to its functions and clinical applications. Serotonin is a neurotransmitter synthesized from tryptophan and localized mainly in the intestines and brain. It regulates various functions like mood, vascular activity, and gastrointestinal motility. Serotonin pathways originate from raphe nuclei and project throughout the brain and spinal cord. There are multiple 5-HT receptor subtypes classified into families based on their structure and function. Serotonin has both central and peripheral roles and drugs like SSRIs, SNRIs, TCAs impact serotonergic neurotransmission. Serotonin agonists and antagonists have clinical uses for conditions like depression, migraines,

1. A PRESENTATION ON
SEROTONIN (5-HT)
PRESENTED TO: DR.M. IKRAM
PRESENTED BY: SABA FARHAD
REGISTRATION NO: FA20-RPY-012
DEPT OF PHARMACY
COMSATS UNIVERSITY ISLAMABAD,
ABBOTTABAD CAMPUS

2. CONTENT
• INTRODUCTION
• BIOSYNTHETIC PATHWAY
• SEROTONIN PATHWAYS IN THE BRAIN
• CLASSIFICATIONS OF 5-HT RECEPTORS
• PERIPHERAL MEDIATED FUNTIONS
• CENTRAL MEDIATED FUNCTIONS
• DRUGS ACTING ON SEROTONERGIC
NEUROTRANSMISSION
• SEROTONIN AGONIST
• SERPTININ ANTAGONISTS
• CLINICAL UTILITY OF SEROTONIN

3. INTRODUCTION
• It is a monoamine neurotransmitter.
•About 90% of body content is found/localized in the
intestines: the rest in brain and platelets.
•It is popularly thought to be a contributor to feelings of
well-being and happiness it is a key mediator in the
physiology of mood, vascular function and gastrointestinal
motility.

4. Biosynthetic part way of 5-HT

5. ⦿The principal centers for serotonergic
neurones are the rostral and caudal raphe
nuclei. From the rostral raphe nuclei axons
ascend to the cerebral cortex, limbic regions
and specifically to the basal ganglia.
⦿Serotonergic nuclei in the brain stem give rise
to descending axons, some of which
terminate in the medulla, while others
descend the spinal cord.

7. 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.

8. PERIPHERAL MEDIATED
PHYSIOLOGICAL FUNCTIONS OF
5-HT RECEPTORS
In periphery:
* Peristalsis
* Vomiting
* Platelet aggregation and haemostasis
* Inflammatory mediator
* Sensitization of nociceptors
* Microvascular control

9. ⦿Many central effects of serotonin receptors
are as follows
⦿Neuronal inhibitions through decrease of
cAMP
⦿Behavioral effects , sleep mood , feeding
thermoregulatory , anxiety
⦿Presynaptic inhibitions
⦿Cerebral vasoconstrictions

10. CLASSIFICATIONS OF 5-HT RECEPTORS
Classification is based on molecular receptor
characterization and cloning.
Four families of 5-HT receptors (5-HT1, 5-HT2 , 5-HT3, 5-HT4-7)
comprising of 14 subtypes have been so far recognized. However
only some of these have been functionally corrected .
All 5-HT receptors ( except 5-HT 3 ) are G protein coupled
receptors which functions through decrease (5-HT 1 )or increasing
(5HT4 , 5HT6, 5-HT7) cAMP Production or by generating IP3/DAG
as second messenger . The 5-HT3 is a ligand gated cation (Na+,k+)
channel which upon activation elicits fast depolarization

13. Drugs acting on serotonergic
neurotransmission
The figure above depicts how serotonin neurotransmission
may be modified at the presynaptic level by inhibiting
degradation, storage or reuptake.

14. • MAO INHIBITORS
Monoamine oxidase is a key enzyme for serotonin,
dopamine and norepinephrine inactivation. MAO inhibitors
prevent inactivation of monoamines within a neuron,
causing excess neurotransmitter to diffuse into the synaptic
space. This class of agents is used in the treatment of
depression (phenelzine, tranylcypromine, selegiline) and
Parkinson’s disease (selegiline).
Dietary restrictions (because of tyramine toxicity) limit their
widespread use.
•Inhibitors of serotonin storage
They interfere with the ability of synaptic vesicles to store
monoamines; displace serotonin, dopamine and
norepinephrine from their storage in presynaptic nerve
terminals. Agents that share this mechanism of action
include amphetamine, methylphenidate and modafinil

15. SNRI
SNRIs mechanism involves blockade of 5-HT and
norepinephrine reuptake in a concentration-dependent
manner. Agents in this class include venlafaxine and
duloxetine, they may be effective for the treatment of
depression in patients in whom SSRIs are ineffective.
SSRIs block the reuptake of serotonin, leading to increased
concentrations of the neurotransmitter in the synaptic cleft and
to an enhanced postsynaptic neuronal activity.
TCAs
Tricyclic antidepressants act by inhibiting reuptake of 5-HT
and norepinephrine from the synaptic cleft by respectively
blocking 5-HT and norepinephrine reuptake transporters,
thereby causing enhancement of postsynaptic response.

16. SEROTONIN AGONIST

17. Serotonin receptors agonists have wide clinical
applications, from treatment of depression to abortive
medications for migraine headache. According to the
receptor they activate, they can be divided into:
5-HT1A agonists
Buspirone is a partial 5-HT1A agonist used clinically for
the treatment of anxiety and depression.
5-HT1B and 5-HT1D agonists
The “triptans” are a drug class useful as abortive
medication for the treatment of acute migraine
headaches. They are very effective in causing cranial
vasoconstriction and decreased release of neuropeptides
involved in “sterile inflammation”.

18. 5-HT2C agonist
Trazodone was previously believed to be a 5-HT2C receptor
antagonist. However, recent publications report that trazodone would
behave as a 5-HT2C agonist. This drug is used generally as
somnorific.
5-HT4 agonists
Cisapride is a serotonin and cholinergic agonist used as a prokinetic
drug, it was withdrawn from the U.S. market because of
cardiovascular toxicity.
Non-selective agonists
Ergotamine activates a more than one subtype of 5-HT receptor, it
binds to 5-HT1A, 5-HT1D, 5-HT1B, D2 and norepinephrine receptors.
Its vasoconstrictor effect makes it a suitable treatment for migraine
attacks.
LSD is a 5-HT1A, 5-HT2A, 5-HT2C, 5-HT5A, 5-HT5, 5-HT6 agonist
that has psychedelic properties.

19. 5-HT2 antagonists
Ketanserin is a 5-HT2A/2C antagonist used for the treatment
of hypertension. In addition to its serotonin antagonism, it has
affinity for alpha-1 receptors, which may contribute to its
antihypertensive effect.

20. Clozapine is an atypical antipsychotic drug that acts as
5-HT2A/2C receptor antagonist with high affinity for
dopamine receptors, the involvement of 5-HT has
possibly increased the chances of greater efficacy and
reduction in negative symptoms of schizophrenia.
Agomelatine is a new antidepressant with agonist
action at the melatonin receptor and antagonism at the
5-HT2C receptor.
5-HT3 antagonists
This class includes drugs such as ondansetron,
palonosetron and others. These agents are particularly
useful in the treatment of chemotherapy induced
nausea and vomiting .

22. CLINICAL UTILITY

23. 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.

24. 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
Confusion, Anxiety, Extreme agitation, Fluctuation in blood
pressure,Increased heart rate many other symptoms
appears.

25. DRUGS USED TO TREAT
SEROTONIN SYNDROME
• Non-specific blocking agents:
methysergide, cyproheptadine.
• Beta –adrenoceptor blockers:
propranolol, pindolol.
• benzodiazepines: lorazepam,
diazepam
• Neuroleptics: chlorpromazine,
haloperidol

26. 1. Get morning sunlight, its more intense and this can boost your
body’s
production melatonin.
2. Get plenty of exercise, researchers have found that exercise
boost serotonin
3. Reduce your stress (both physical and emotional), prolonged
stress produce adrenaline and cortisol which interfere with
serotonin
4. Eating foods that are high in protein because of high percentage
of
tryptophan
5. Also food containing carbohydrates as they produce insulin
which helps tryptophan go into the brain