AUTACOID

Autos: self akos: relief

“A chemical substance produced by one type of cell that affects the
function of different types of cells in the same region ”.

1. Eicosanoids: Prostaglandins (PG)

Tromboxanes (TX)
Leucotrienes (LT) Generated
“de novo”
2. Nitric oxide (NO) and platelet activating factor (PAF)

3. Polipeptides: Angiotensine and Bradykinin.

4. Amines: Histamine and serotonin stored

 SEROTONINE
5-HYDROXITRYPTAMINE

Localization: - Enterochromaffin cells (gut) (90%)

- platelets
- mast cells
- brain (1-2%)
 Synthesis of 5-HT In enterochromaffin
cells and neurons
Diet
 Metabolism of 5-HT

Serotonine
Regulation: Monoaminooxidase

Diet (tryptophan,
tyrosine,
phenylalanine,
leucine)
O2
Aldehido deshydrogenase
Daily fluctuations
Pharmacologycal

5-hydroxiindolacetyc acid
5-HT receptor subtypes Distribution
5-HT1 (5-HT1A, 5-HT1B, 5-HT1D) CNS, blood vessels

5-HT2 (5-HT2A, 5-HT2B, 5-HT2C) CNS and PNS, smooth

muscle, platelets
5-HT3 (5-HT3A, 5-HT3B) CNS, PNS

5-HT4 CNS, PNS

5-HT5 CNS

5-HT6 CNS

5-HT7 CNS, gi tract, blood

vessels
Pharmacological actions of 5-HT

5-HT1A
CNS-Inhibitory (pre and
postsynaptic)
Anxyolisis, sleep, hyperfagia

5-HT1D
CNS- Inhibitory (presynaptic)
Blood vessels- Vassoconstriction
 Pharmacological actions of 5-HT

5-HT2 receptors

IP3, DAG

5-HT2A receptors
Smooth muscle- contraction
Platelets-aggregation, vassodilation/Vassoconstriction
CNS- excitation- psicosis
Pharmacological actions of 5-HT

5-HT3
CNS- (area postrema) Emesis
Anxiety
PNS- nociceptive neurones-pain

5-HT4
PNS- gastrointestinal motility

CNS- Neuronal excitation

+ +
Pharmacological actions of 5-HT

5-HT6
CNS- increases cholinergic
transmission (memory)

+ 5-HT7
CNS
Gi tract (Unknown)
 Pharmacological actions of 5-HT

5-HT storage and release in the brain

-Mood
-Sleep/awake cycle
- Appetite
5-HT and mood
5-HT and weight loss

Weight (kg)
Fenfluramine
and
Phentermine

Time (weeks)
5-HT in sleep-waking cycle
Clinical use of 5-HT drugs (Antidepressants)
SSRI (selective serotonine reuptake inhibitors)

Fluoxetine Citalopram

Paroxetine
Sertraline
 Clinical use of 5-HT drugs
Anxiety 5-HT1A agonist Buspirone

Migraine 5-HT1D agonist Sumatriptan,

Zolmitriptan

Migraine profilaxis 5-HT2 antagonist Dihidroergotamine

Esquizophrenia 5-HT2A antgonist Risperidone

Antiemetics 5-HT3 antagonist Ondansetron

(quimiotherapy) Granisetron
Tropisetron

Peristaltism 5-HT4 agonists Metoclopramide

(procinetics) Tegaserod
Neurotransmitters and receptors involved in emesis control

NEUROTRANSMITTERS RECEPTORS

DOPAMINE D2

SEROTONINE 5HT3

HISTAMINE H1

ACETYLCHOLINE MUSCARINICS
 Factors involved in control of vomiting

Stimuli
Sensory afferents
Pain,
images
Odour
Emotions
Chemoreceptor
Vomiting
Vestibular nuclei trigger zone
cinetosis centre
H1 and M1 D2 and 5-HT3
M1

Solitary tract
toxins nucleus 5-HT3 antagonists
Visceral afferents
H1 and M1 H1 antagonists
Stimuli from 5-HT3? D2 antagonists
the gi system M1 antagonists
 ANTIEMETIC DRUGS
Metoclopramide
D2 ANTAGONISTS
Domperidone
Thietylperazine
Haloperidol

ANTAGONISTAS 5-HT3 Ondansetron

Granisetron
Tropisetron

ANTAGONISTAS H1 Cinarizine
Ciclizine
Dimenhidrinate
 ANTIEMETIC DRUGS

M1 ANTAGONISTS Hioscine, escopolamine

CORTICOSTEROIDS Dexametasone
Metilprednisolone

CANNABINOIDS Nabilona
 CLINICAL USE OF ANTIEMETIC DRUGS

D2 ANTAGONISTS
Vomits induced by radiation, virus, pregnancy (metoclopramide)
5-HT3 antagonists
- Vomits induced by quimiotherapy (treatment of cancer)
- Vomits post surgery
- Vomits induced by radiation
H1 antagonists
- Motion sickness
- Vestibular unbalance
- Early morning nausea during pregnancy (doximalmine and prometacine)
M1 antagonists
-Motion sickness (hioscine)
Cannabinoids
- Vomits induced by quimiotherapy (treatment of cancer)