SlideShare a Scribd company logo
1 of 22
A PRESENTATION ON
AN OVERVIEW ON THE INVOLVMENT OF
SEROTONIN (5-HT) IN CENTRALLY AND
PERIPHERALLY MEDIATED
PHYISIOLOGICAL FUNCTIONS
BY JOSHUA K NWEKE
AMINU ABUBAKAR KENDE
KANISHK LUHACH
DEPT OF PHARMACY
IEC GROUP OF INSTITUTIONS.
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.
• This explains the number of therapeutic agents that act
targeting the serotonergic system such as: 5-HT3
antagonists, SSRIs and triptans.
Formula: C10H12N2O
Molar mass: 176.2151 g/mol
Melting point: 121 °C
Boiling point: 416 °C
IUPAC ID: 3-(2-aminoethyl)-1H-indol-5-ol, 5-
Hydroxytryptamine
Biosynthetic part way of 5-HT
CLASSIFICATIONS OF 5-HT RECEPTORS
Gaddum and Picarelli (1957) classified 5-HT receptors into
musculotropic(D type) and neurotropic (M type) based on their
blockade by Dibenzyline (phenoxybenzinamine).
Modern 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
PERIPHERAL MEDIATED
PHYSIOLOGICAL FUNCTIONS OF
5-HT RECEPTORS
In periphery:
* Peristalsis
* Vomiting
* Platelet aggregation and haemostasis
* Inflammatory mediator
* Sensitization of nociceptors
* Microvascular control
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
 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.
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.
• 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
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.
SEROTONIN AGONIST
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”.
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.
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.
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 .
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
CONCLUSION
•From the above presentations we can conclude the following
5-HT is one of the most important neurotransmitters in the CNS
and PNS as well
It also plays a major role in the maintenance of homeostasis ,
control of appetite, sleep, mood, hallucinations, stereotyped
behavior, pain perception and vomiting.
Looking into the drugs which acts on 5-HT receptors it becomes
very clear that for a effective and save management of any
neurological conditions use of drugs which affect serotonin is of
great importance .
Drugs which acts on serotonin are relatively safer than those
acting on dopamine and nor epinephrine
SEROTONIN (5-HT) NEUROTRANSMITTER �

More Related Content

What's hot

Neurotransmitters
NeurotransmittersNeurotransmitters
Neurotransmitters
vacagodx
 
Serotonin receptors
Serotonin receptorsSerotonin receptors
Serotonin receptors
FarazaJaved
 

What's hot (20)

Dopamine Receptors by Manisha
Dopamine Receptors by ManishaDopamine Receptors by Manisha
Dopamine Receptors by Manisha
 
Neurotransmitters
NeurotransmittersNeurotransmitters
Neurotransmitters
 
Dopaminegic receptors
Dopaminegic receptorsDopaminegic receptors
Dopaminegic receptors
 
Serotonin receptors
Serotonin receptorsSerotonin receptors
Serotonin receptors
 
Glutamate recp
Glutamate recpGlutamate recp
Glutamate recp
 
Dopamine
DopamineDopamine
Dopamine
 
Pharmacology of dopamine
Pharmacology of dopaminePharmacology of dopamine
Pharmacology of dopamine
 
Glutamate receptors
Glutamate receptorsGlutamate receptors
Glutamate receptors
 
Glutamate
GlutamateGlutamate
Glutamate
 
Neurotransmitters in CNS
Neurotransmitters in CNSNeurotransmitters in CNS
Neurotransmitters in CNS
 
Serotonin
SerotoninSerotonin
Serotonin
 
GABA, glutamate receptors and their modulation
GABA, glutamate receptors and their modulationGABA, glutamate receptors and their modulation
GABA, glutamate receptors and their modulation
 
Serotonin.dr.asa
Serotonin.dr.asaSerotonin.dr.asa
Serotonin.dr.asa
 
Dopamine
DopamineDopamine
Dopamine
 
Serotonin : diseases and therapeutics
Serotonin : diseases and therapeuticsSerotonin : diseases and therapeutics
Serotonin : diseases and therapeutics
 
Glutamate muztaba
Glutamate muztabaGlutamate muztaba
Glutamate muztaba
 
neurotransmitter gaba
neurotransmitter gabaneurotransmitter gaba
neurotransmitter gaba
 
Neurotransmitters
NeurotransmittersNeurotransmitters
Neurotransmitters
 
Serotonin pharmacology
Serotonin  pharmacologySerotonin  pharmacology
Serotonin pharmacology
 
Neurotransmitter
NeurotransmitterNeurotransmitter
Neurotransmitter
 

Viewers also liked

An introduction of serotonin
An introduction of serotoninAn introduction of serotonin
An introduction of serotonin
Nep Su Warnam
 
The adrenal gland, catecholamine synthesis
The adrenal gland, catecholamine synthesisThe adrenal gland, catecholamine synthesis
The adrenal gland, catecholamine synthesis
Atif Khirelsied
 
Pharmacokinetics and Pharmacodynamics
Pharmacokinetics and PharmacodynamicsPharmacokinetics and Pharmacodynamics
Pharmacokinetics and Pharmacodynamics
Bhaswat Chakraborty
 
Pharmacology - Parkinsonism
Pharmacology - ParkinsonismPharmacology - Parkinsonism
Pharmacology - Parkinsonism
MBBS IMS MSU
 

Viewers also liked (20)

Glutamate
GlutamateGlutamate
Glutamate
 
An introduction of serotonin
An introduction of serotoninAn introduction of serotonin
An introduction of serotonin
 
5-Hydroxytyptamine (Serotonin)
5-Hydroxytyptamine (Serotonin)5-Hydroxytyptamine (Serotonin)
5-Hydroxytyptamine (Serotonin)
 
Adrenergic receptors
Adrenergic receptorsAdrenergic receptors
Adrenergic receptors
 
Catecholamines
CatecholaminesCatecholamines
Catecholamines
 
Adrenergic receptors and its modulators
Adrenergic receptors and its modulatorsAdrenergic receptors and its modulators
Adrenergic receptors and its modulators
 
The adrenal gland, catecholamine synthesis
The adrenal gland, catecholamine synthesisThe adrenal gland, catecholamine synthesis
The adrenal gland, catecholamine synthesis
 
Neuropharmacology: Catecholamines
Neuropharmacology: CatecholaminesNeuropharmacology: Catecholamines
Neuropharmacology: Catecholamines
 
Catecholamines & noncatecholamines
Catecholamines & noncatecholaminesCatecholamines & noncatecholamines
Catecholamines & noncatecholamines
 
Histamine
HistamineHistamine
Histamine
 
Dopamine
DopamineDopamine
Dopamine
 
Bromocriptine
BromocriptineBromocriptine
Bromocriptine
 
5-HT Pharmacology - drdhriti
5-HT Pharmacology - drdhriti5-HT Pharmacology - drdhriti
5-HT Pharmacology - drdhriti
 
Dopamine And Pathways
Dopamine And PathwaysDopamine And Pathways
Dopamine And Pathways
 
Bromocriptine for Special Population - Adult ADHD
Bromocriptine for Special Population - Adult ADHDBromocriptine for Special Population - Adult ADHD
Bromocriptine for Special Population - Adult ADHD
 
Pharmacokinetics and Pharmacodynamics
Pharmacokinetics and PharmacodynamicsPharmacokinetics and Pharmacodynamics
Pharmacokinetics and Pharmacodynamics
 
Antipsychotics - Pharmacology
Antipsychotics - PharmacologyAntipsychotics - Pharmacology
Antipsychotics - Pharmacology
 
Antipsychotics
AntipsychoticsAntipsychotics
Antipsychotics
 
Neuroleptics (antipsychotics)
Neuroleptics (antipsychotics)Neuroleptics (antipsychotics)
Neuroleptics (antipsychotics)
 
Pharmacology - Parkinsonism
Pharmacology - ParkinsonismPharmacology - Parkinsonism
Pharmacology - Parkinsonism
 

Similar to SEROTONIN (5-HT) NEUROTRANSMITTER

Similar to SEROTONIN (5-HT) NEUROTRANSMITTER (20)

serotonin.pptx
serotonin.pptxserotonin.pptx
serotonin.pptx
 
neurohumoraltransmissionincns-210526115354.pdf
neurohumoraltransmissionincns-210526115354.pdfneurohumoraltransmissionincns-210526115354.pdf
neurohumoraltransmissionincns-210526115354.pdf
 
Neurohumoral transmission in CNS
Neurohumoral transmission in CNSNeurohumoral transmission in CNS
Neurohumoral transmission in CNS
 
CNS stimulants
CNS stimulantsCNS stimulants
CNS stimulants
 
Anti Depressive Drugs
Anti Depressive DrugsAnti Depressive Drugs
Anti Depressive Drugs
 
Antidepressants.pptx
Antidepressants.pptxAntidepressants.pptx
Antidepressants.pptx
 
Anti depression
Anti depressionAnti depression
Anti depression
 
central nervous system
central nervous system central nervous system
central nervous system
 
Central Nervous System Stimulants presentation
Central Nervous System Stimulants presentationCentral Nervous System Stimulants presentation
Central Nervous System Stimulants presentation
 
Sedatives and hypnotics (1)
Sedatives and hypnotics (1)Sedatives and hypnotics (1)
Sedatives and hypnotics (1)
 
Sedatives and hypnotics (1)
Sedatives and hypnotics (1)Sedatives and hypnotics (1)
Sedatives and hypnotics (1)
 
Antidepressants & anxiolytics
Antidepressants & anxiolyticsAntidepressants & anxiolytics
Antidepressants & anxiolytics
 
Antidepressants Tca Ssri
Antidepressants   Tca SsriAntidepressants   Tca Ssri
Antidepressants Tca Ssri
 
Serotonin & Their antagonists
Serotonin & Their antagonistsSerotonin & Their antagonists
Serotonin & Their antagonists
 
Serotonin and its role in psychiatry Aditya.pptx
Serotonin and its role in psychiatry Aditya.pptxSerotonin and its role in psychiatry Aditya.pptx
Serotonin and its role in psychiatry Aditya.pptx
 
SEROTONIN for better understanding .pptx
SEROTONIN for better understanding .pptxSEROTONIN for better understanding .pptx
SEROTONIN for better understanding .pptx
 
Psychopharmacology.pptx
Psychopharmacology.pptxPsychopharmacology.pptx
Psychopharmacology.pptx
 
antidepressant drugs.pptx
antidepressant drugs.pptxantidepressant drugs.pptx
antidepressant drugs.pptx
 
2.CNS Stimulants.pptx
2.CNS Stimulants.pptx2.CNS Stimulants.pptx
2.CNS Stimulants.pptx
 
Seminar On Antidepressants
Seminar On AntidepressantsSeminar On Antidepressants
Seminar On Antidepressants
 

More from Aminu Kende

More from Aminu Kende (12)

HEALTH COMMUNICATION & MASS MEDIA IN PUBLIC HEALTH
HEALTH COMMUNICATION & MASS MEDIA IN PUBLIC HEALTHHEALTH COMMUNICATION & MASS MEDIA IN PUBLIC HEALTH
HEALTH COMMUNICATION & MASS MEDIA IN PUBLIC HEALTH
 
Healthcare Ethics
Healthcare Ethics Healthcare Ethics
Healthcare Ethics
 
Sexually Transmitted Infections
Sexually Transmitted InfectionsSexually Transmitted Infections
Sexually Transmitted Infections
 
Basic Concept of Epidemiology
Basic Concept of EpidemiologyBasic Concept of Epidemiology
Basic Concept of Epidemiology
 
Drugs And Magic Remedies Act
Drugs And Magic Remedies ActDrugs And Magic Remedies Act
Drugs And Magic Remedies Act
 
Nanosuspension
NanosuspensionNanosuspension
Nanosuspension
 
Macrolides
MacrolidesMacrolides
Macrolides
 
Patent act 1970 with amendment
Patent act 1970 with amendmentPatent act 1970 with amendment
Patent act 1970 with amendment
 
NEOPLASM
NEOPLASMNEOPLASM
NEOPLASM
 
Inborn erros of amino acid metabolism
Inborn erros of amino acid metabolismInborn erros of amino acid metabolism
Inborn erros of amino acid metabolism
 
Endocrine pharmacology in Brief
Endocrine pharmacology in Brief Endocrine pharmacology in Brief
Endocrine pharmacology in Brief
 
NOVEL DRUG DELIVERY SYSTEM REVIEW
NOVEL DRUG DELIVERY SYSTEM REVIEW�NOVEL DRUG DELIVERY SYSTEM REVIEW�
NOVEL DRUG DELIVERY SYSTEM REVIEW
 

Recently uploaded

會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽
會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽
會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽
中 央社
 
Financial Accounting IFRS, 3rd Edition-dikompresi.pdf
Financial Accounting IFRS, 3rd Edition-dikompresi.pdfFinancial Accounting IFRS, 3rd Edition-dikompresi.pdf
Financial Accounting IFRS, 3rd Edition-dikompresi.pdf
MinawBelay
 

Recently uploaded (20)

Basic Civil Engineering notes on Transportation Engineering, Modes of Transpo...
Basic Civil Engineering notes on Transportation Engineering, Modes of Transpo...Basic Civil Engineering notes on Transportation Engineering, Modes of Transpo...
Basic Civil Engineering notes on Transportation Engineering, Modes of Transpo...
 
Capitol Tech Univ Doctoral Presentation -May 2024
Capitol Tech Univ Doctoral Presentation -May 2024Capitol Tech Univ Doctoral Presentation -May 2024
Capitol Tech Univ Doctoral Presentation -May 2024
 
Essential Safety precautions during monsoon season
Essential Safety precautions during monsoon seasonEssential Safety precautions during monsoon season
Essential Safety precautions during monsoon season
 
size separation d pharm 1st year pharmaceutics
size separation d pharm 1st year pharmaceuticssize separation d pharm 1st year pharmaceutics
size separation d pharm 1st year pharmaceutics
 
Operations Management - Book1.p - Dr. Abdulfatah A. Salem
Operations Management - Book1.p  - Dr. Abdulfatah A. SalemOperations Management - Book1.p  - Dr. Abdulfatah A. Salem
Operations Management - Book1.p - Dr. Abdulfatah A. Salem
 
The Last Leaf, a short story by O. Henry
The Last Leaf, a short story by O. HenryThe Last Leaf, a short story by O. Henry
The Last Leaf, a short story by O. Henry
 
ĐỀ THAM KHẢO KÌ THI TUYỂN SINH VÀO LỚP 10 MÔN TIẾNG ANH FORM 50 CÂU TRẮC NGHI...
ĐỀ THAM KHẢO KÌ THI TUYỂN SINH VÀO LỚP 10 MÔN TIẾNG ANH FORM 50 CÂU TRẮC NGHI...ĐỀ THAM KHẢO KÌ THI TUYỂN SINH VÀO LỚP 10 MÔN TIẾNG ANH FORM 50 CÂU TRẮC NGHI...
ĐỀ THAM KHẢO KÌ THI TUYỂN SINH VÀO LỚP 10 MÔN TIẾNG ANH FORM 50 CÂU TRẮC NGHI...
 
Morse OER Some Benefits and Challenges.pptx
Morse OER Some Benefits and Challenges.pptxMorse OER Some Benefits and Challenges.pptx
Morse OER Some Benefits and Challenges.pptx
 
philosophy and it's principles based on the life
philosophy and it's principles based on the lifephilosophy and it's principles based on the life
philosophy and it's principles based on the life
 
Dementia (Alzheimer & vasular dementia).
Dementia (Alzheimer & vasular dementia).Dementia (Alzheimer & vasular dementia).
Dementia (Alzheimer & vasular dementia).
 
Post Exam Fun(da) Intra UEM General Quiz - Finals.pdf
Post Exam Fun(da) Intra UEM General Quiz - Finals.pdfPost Exam Fun(da) Intra UEM General Quiz - Finals.pdf
Post Exam Fun(da) Intra UEM General Quiz - Finals.pdf
 
Behavioral-sciences-dr-mowadat rana (1).pdf
Behavioral-sciences-dr-mowadat rana (1).pdfBehavioral-sciences-dr-mowadat rana (1).pdf
Behavioral-sciences-dr-mowadat rana (1).pdf
 
An overview of the various scriptures in Hinduism
An overview of the various scriptures in HinduismAn overview of the various scriptures in Hinduism
An overview of the various scriptures in Hinduism
 
Danh sách HSG Bộ môn cấp trường - Cấp THPT.pdf
Danh sách HSG Bộ môn cấp trường - Cấp THPT.pdfDanh sách HSG Bộ môn cấp trường - Cấp THPT.pdf
Danh sách HSG Bộ môn cấp trường - Cấp THPT.pdf
 
“O BEIJO” EM ARTE .
“O BEIJO” EM ARTE                       .“O BEIJO” EM ARTE                       .
“O BEIJO” EM ARTE .
 
Post Exam Fun(da) Intra UEM General Quiz 2024 - Prelims q&a.pdf
Post Exam Fun(da) Intra UEM General Quiz 2024 - Prelims q&a.pdfPost Exam Fun(da) Intra UEM General Quiz 2024 - Prelims q&a.pdf
Post Exam Fun(da) Intra UEM General Quiz 2024 - Prelims q&a.pdf
 
BỘ LUYỆN NGHE TIẾNG ANH 8 GLOBAL SUCCESS CẢ NĂM (GỒM 12 UNITS, MỖI UNIT GỒM 3...
BỘ LUYỆN NGHE TIẾNG ANH 8 GLOBAL SUCCESS CẢ NĂM (GỒM 12 UNITS, MỖI UNIT GỒM 3...BỘ LUYỆN NGHE TIẾNG ANH 8 GLOBAL SUCCESS CẢ NĂM (GỒM 12 UNITS, MỖI UNIT GỒM 3...
BỘ LUYỆN NGHE TIẾNG ANH 8 GLOBAL SUCCESS CẢ NĂM (GỒM 12 UNITS, MỖI UNIT GỒM 3...
 
How to Manage Notification Preferences in the Odoo 17
How to Manage Notification Preferences in the Odoo 17How to Manage Notification Preferences in the Odoo 17
How to Manage Notification Preferences in the Odoo 17
 
會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽
會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽
會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽會考英聽
 
Financial Accounting IFRS, 3rd Edition-dikompresi.pdf
Financial Accounting IFRS, 3rd Edition-dikompresi.pdfFinancial Accounting IFRS, 3rd Edition-dikompresi.pdf
Financial Accounting IFRS, 3rd Edition-dikompresi.pdf
 

SEROTONIN (5-HT) NEUROTRANSMITTER

  • 1. A PRESENTATION ON AN OVERVIEW ON THE INVOLVMENT OF SEROTONIN (5-HT) IN CENTRALLY AND PERIPHERALLY MEDIATED PHYISIOLOGICAL FUNCTIONS BY JOSHUA K NWEKE AMINU ABUBAKAR KENDE KANISHK LUHACH DEPT OF PHARMACY IEC GROUP OF INSTITUTIONS.
  • 2. 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. • This explains the number of therapeutic agents that act targeting the serotonergic system such as: 5-HT3 antagonists, SSRIs and triptans.
  • 3. Formula: C10H12N2O Molar mass: 176.2151 g/mol Melting point: 121 °C Boiling point: 416 °C IUPAC ID: 3-(2-aminoethyl)-1H-indol-5-ol, 5- Hydroxytryptamine
  • 5. CLASSIFICATIONS OF 5-HT RECEPTORS Gaddum and Picarelli (1957) classified 5-HT receptors into musculotropic(D type) and neurotropic (M type) based on their blockade by Dibenzyline (phenoxybenzinamine). Modern 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
  • 6.
  • 7. PERIPHERAL MEDIATED PHYSIOLOGICAL FUNCTIONS OF 5-HT RECEPTORS In periphery: * Peristalsis * Vomiting * Platelet aggregation and haemostasis * Inflammatory mediator * Sensitization of nociceptors * Microvascular control
  • 8. 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
  • 9.
  • 10.  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.
  • 11.
  • 12. 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.
  • 13. • 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
  • 14. 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 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”.
  • 17. 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.
  • 18. 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.
  • 19. 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 .
  • 20. 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
  • 21. CONCLUSION •From the above presentations we can conclude the following 5-HT is one of the most important neurotransmitters in the CNS and PNS as well It also plays a major role in the maintenance of homeostasis , control of appetite, sleep, mood, hallucinations, stereotyped behavior, pain perception and vomiting. Looking into the drugs which acts on 5-HT receptors it becomes very clear that for a effective and save management of any neurological conditions use of drugs which affect serotonin is of great importance . Drugs which acts on serotonin are relatively safer than those acting on dopamine and nor epinephrine