Serotonin pharmacology

1. Omkar Patnaik
Roll- 21064
Omkar Patnaik
Roll- 21064

2. ▪ History
▪ Synthesis, Storage, Reuptake, Release & Destruction
▪ Receptors
▪ Actions
▪ Pathophysiologic roles
▪ Drugs affecting 5HT
▪ Drugs and Indications
▪ References

3. ▪ In 1935, Vittorio Erspamer showed an monoamine extract from enterochromaffin cells
that made intestines contract. He named it “enteramine”.
▪ In 1948, Maurice Rapport, Arda Green, and Irvine Page of Cleveland Clinic extracted a
vasoconstrictor from blood serum. They called it “serotonin”.
▪ In 1952, both were proved to be the same chemical substance - 5 hydroxy tryptamine.
▪ From then 5HT became the preferred name.
▪ Synonyms: 3-(β-aminoethyl)-5-hydroxyindole
thrombotin
substance DS

6. ▪ Previously
▪ Then, classified on basis of high or low affinity to tritium(3H) in radioligand binding.
5HT-R
M-Type
Morphine
blockade
D-Type
Dibenzyline
blockade

7. ▪ Based on molecular
characterisation and cloning
of receptor cDNAs
▪ 14 subtypes known
5HT-R
5HT1
1A, B, D, E, F, P
GPCRs (Gi/Go)
5HT2
2A, B, C
GPCRs (Gq)
5HT3
Ligand gated ion
channel receptor
5HT4-7
4, 5,6, 7
GPCRs(Gs)

9. ▪ CVS
▪ Visceral smooth muscles
▪ Glands
▪ Nerve endings
▪ Adrenal medulla
▪ Respiration
▪ Platelets
▪ CNS

10. ▪ IV 5HT produce no action as it cannot cross BBB
▪ But it primarily acts as inhibitory NT
▪ If given intrathecally produces:
1. Sleepiness
2. Body temperature changes
3. Hunger
4. Behavioral effects

11. ▪ Neurotransmitter
▪ Melatonin precursor
▪ Neuroendocrine function
▪ Nausea & vomiting
▪ Migraine
▪ Haemostasis
▪ Raynaud’s phenomenon
▪ Hypertension
▪ Intestinal motility
▪ Carcinoid syndrome

12. ▪ 5HT - no therapeutic use
▪ 5HT precursor
▪ Synthesis inhibitor
▪ Storage inhibitor
▪ Uptake inhibitor
▪ Degradation inhibitor
▪ Neuronal degeneration
▪ 5HT-R agonists
▪ 5HT-R antagonists

13. ▪ 5HT precursor
▪ In natural diet
▪ Supplements used(not much research)
▪ Early research in people hints that L-
tryptophan supplements may be helpful for:
• Obstructive sleep apnea(OSA)
• Seasonal affective disorder (SAD)
• Premenstrual dysphoric syndrome(PMDD)
• Insomnia
• Depression

14. ▪ Synthesis inhibitor
▪ Fenclonine
▪ Tryptophan hydroxylase inhibitor
▪ In preclinical studies, used to deplete
5HT
▪ Was used experimentally to treat
carcinoid syndrome
▪ Now not used due to side effects

15. ▪ Reserpine
▪ Storage inhibitor
▪ The antihypertensive actions of Reserpine are a result of
its ability to deplete catecholamines from peripheral
sympathetic nerve endings
▪ Mild essential hypertension
▪ Also useful as adjunctive therapy with other
antihypertensive agents in the more severe forms of
hypertension
▪ relief of symptoms in agitated psychotic states (e.g.,
schizophrenia), primarily in those individuals unable to
tolerate phenothiazine derivatives or in those who also
require antihypertensive medication.

16. Used for
1. Depression(DOC)
2. PMDD(DOC)
3. Neurosis(DOC)
4. Postmenopausal hot
flashes
5. OCD
6. Phobia
7. PTSD
8. GAD
9. Anorexia
10.Bulimia

17. ▪ 2nd line Tx for atypical depression
▪ Rarely used(SE- hepatotoxicity)
▪ Can cause cheese reaction and
serotonin syndrome
▪ contraindicated with SSRI, SNRI, TCA,
Amphetamine, methylphenidate,
Opioids, Pethidine, Tramadol.

18. ▪ D-Lysergic acid diethylamide(LSD)
▪ Azapirones- partial agonist of 5-HT1A receptor in brain
1. Buspirone
2. Gepirone
3. Ipsapirone
▪ Sumatriptan- selective 5-HT1D/1B agonist
▪ Cisapride, Renzapride- selective 5HT4 agonist

19. 1. LSD
- No approved indications for LSD-assisted therapy exist today.
- past non FDA approved indications:
depressive disorders including those with conversion phobia,
neurosis,
manic-depression
reactive depression,
cyclothymic (obsessional) and passive-aggressive (obsessional) compulsive sexual deviation
addiction,
psychoneurotic disorders,
pan-neuroticism (including schizophrenia),
Mixed, borderline or latent and personality disorders (especially transient situational)

20. 2. Azapirones - anti anxiety without sedation
3. Sumatriptan – most effective treatment for acute migraine
attacks
4. Cisapride – increases GI motility.
Symptomatic treatment of adult patients with nocturnal heartburn
due to gastroesophageal reflux disease.
5. Rinzapride -
currently in Phase III clinical development in the United States for
the treatment of constipation-predominant irritable bowel syndrome
(IBS-C).
It has been suggested that renzapride is effective in the treatment
of irritable bowel syndrome with alternating stool pattern.

21. ▪ Ergot derivatives
1. Ergotamine
2. LSD
3. 2-Bromo LSD
4. Methysergide
▪ Adrenergic ⍺ blockers
(phenoxybenzamine)
▪ Antihistamines
1. Cyproheptadine
2. Cinnarizine
▪ Chlorpromazine
▪ Morphine
▪ Ketanserin
▪ Risperidone
▪ Ondansetron

22. 1. Cyproheptadine –
- used in allergies
- controls intestinal manifestations of carcinoid and post gastrectomy dumping syndrome
2. Methysergide –
- used prophylactically in migraine and other vascular headaches
- to antagonize serotonin in the carcinoid syndrome, postgastrectomy dumping syndrome.
3. Ketanserin -
- classified as an antihypertensive by the WHO & NIH
- was used to reverse pulmonary hypertension caused by protamine (which in turn w as administered to reverse the
effects of heparin overdose).
4. Ritanserin –
- used in trials studying the treatment of Cocaine-Related Disorders.
- effective in the treatment of a variety of syndromes related to anxiety and depression.
- improves the subjective quality of sleep and decreases portal pressure.

23. 5. Clozapine –
- treatment of severely ill patients with schizophrenia who fail to respond
adequately to standard antipsychotic treatment.
6. Risperidone –
▪ Schizophrenia (in adults and children aged 13 and up)
▪ Bipolar I acute manic or mixed episodes as monotherapy (in adults and
children aged ten and up)
▪ Bipolar I acute manic or mixed episodes adjunctive with lithium or valproate
(in adults)
▪ Autism-associated irritability (in children aged five and up)
7. Ondansetron –
▪ Prevention of chemotherapy-induced & radiation-induced nausea and
vomiting
▪ the prevention of postoperative nausea and vomiting
▪ off-label use for the prevention of nausea and vomiting associated with
pregnancy.

24. ▪ Used in PPH(Ergometine IM/IV)
▪ Used in migraine(Ergotamine &
Dihydroergotamine)
▪ Contraindications : IHD, HTN, Epilepsy, hepatic
or renal impairment & pregnancy.

25. ▪ Essentials of medical pharmacology - KD Tripathi
▪ https://www.google.co.in/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwih
06yduIv-
AhVgUGwGHa6SDa0QFnoECAwQAQ&url=https%3A%2F%2Fen.wikipedia.org%2Fwiki
%2FSerotonin&usg=AOvVaw3j1cDlaRO88SQFPQR5KbKq
▪ https://www.ncbi.nlm.nih.gov/books/NBK539848/#:~:text=Monoamine%20oxidase%20inhi
bitors%20(MAOIs)%20are,and%20depression%20with%20atypical%20features.
▪ https://pubmed.ncbi.nlm.nih.gov/6198047/
▪ https://www.webmd.com/vitamins-and-supplements/l-tryptophan-uses-and-risks