Pharmacology

1. SEROTONIN BY MISHI
GROUP 4

2. OUTLINE;
1. Introduction.
2. Synthesis and degeneration.
3. Receptor and their actions.
4. Pharmacological action.
5. Pathophysiological actions.

3. INTRO;
Is a neurotransmitter and autacoid from tryptophan.
Found in the; GIT cells, neurons ,platelets.
Involved in ; migraine, psychosis, sleep&GI
disorders.
Known as enteramine as 90% of human body’s total
serotonin is located in the enterochromaffin cells in
the alimentary canal used to regulate intestinal
mov’nt.

4. SYNTHESIS & DEGENERATION;
Serotonin secreted from the enterochromaffin cells ,
find its way out of tissues into the blood. There it is
actively taken up by blood platelets thro’ their
serotonin transporters, which stores it .
 when the platelets bind to a clot, they release
serotonin where it serve as a vasoconstrictor & help to
regulate homeostasis and blood clotting.
Being monoamine like catecholamine is metabolized
by MOA & COMT[catechol-o- methyltransferase].

5. CONT;
Tryptophan
hydroxylase
5-hydroxytryptophan
decarboxylase
5-hydroxytryptamine[5-ht]
moa
dehydrogenase[comt]
5-hydroxytryptophol 5-hydroxyindole acetatic
acid[5-HIAA]

6. RECEPTOR & THEIR ACTIONS;
ARE AROUND 10-15 BUT ONLY 3-4 ON WHICH DRUGS
ARE SYNTHESISED.

7. CONT;
5-HT1;
1A,1B,1D,1E,1F.
Inhibitory.
1A(hippocampus& raphe nuclei),1B( Substantial nigra),1D(cranial blood
vessels ) ,1E(cortex),1F(brain & peripheral).
Dec 5ht release, contraction of cranial bvs,dec release of peptides from
nerve endings.
Buspirone ,triptans ,ergonemetrin.

8. CONT;
5-HT2;
2A,2B,2C.
Excitatory.
2A(platelets ,smooth muscles, cerebral
cortex),2B(fundus),2C(choroid plexus).
Platelets aggregations, smooth muscle contraction,csf production,
neuronal excitation.
Ketanserin, methysergide,cryproheptadine.

9. CONT;
5-HT3;
Activate ion channels (NA+,K+).
CTZ,NTs,parasympa nerve terminal, git.
Vomiting, stimulate neurons,peristalisis.
Odansetron, granisetron.

10. CONT;
5-HT4;
Excitatory.
Git,cns(hippocampus).
Peristalisis,enhance git secretion, increase intracellular conc. of camp.
Renzapride,metoclopramide,prucaloride.
5-HT5;
Inhibitory.
Hippocampus.
Dec intracellular conc. of camp.

11. CONT;
5-HT6;
Excitatory.
Stratum.
Increase intracellular conc. of camp.
5-HT7;
Excitatory.
Hypothalamus, intestines.
Increase intracellular conc. of camp.

12. PHARMACOLOGICAL ACTIONS;
CVS:
its response is seen on iv injection :
 Early sharp fall in BP—due to coronary chemo reflex.
 Brief rise in BP—due to vasoconstriction and increased cardiac output
 Prolonged fall in BP—due to arteriolar dilatation and extravasation of
fluid.
 But has no role in physiological regulation of Bp.
On GIT smooth muscles:
 Increased contractions and secretions.
On nerve endings and adrenal medulla:
 Stimulation and release of CAs.

13. CONT;
On GIT smooth muscles:
 Increased contractions and secretions.
On nerve endings and adrenal medulla:
Stimulation and release of CAs.
On respiratory tract:
 Stimulation of resp and hyperventilation
Platelets:
Changes in shape of platelets and aggregation.

14. CONT;
CNS:
 poorly crosses BBB hence no central effect on i.v injection.
 Serves as a transmitter primarily inhibitory.
 Direct injection in the brain produces sleepiness, changes in body
temperature, hunger and a variety of behavioural effects.

15. PATHOPHYSIOLOGICAL ROLES;
Neurotransmitter:
 Involved in sleep, temperature regulation, thought, cognitive
function, behaviour and mood (imbalance may result in affective
disorders and schizophrenia), vomiting and pain perception.
Precursor of melatonin in pineal gland.
 Regulate biological clock and maintain circadian rhythm.
Neuroendocrine function:
 Control release of anterior pituitary hormones.
 Nausea and vomiting are evoked.

16. CONT;
Migraine
 Initiate the vasoconstrictor phase of migraine and to participate in
neurogenic inflammation of the affected blood vessels.
Maintain homeostasis:
 Accelerates platelet aggregation and clot formation.
 Its contractile action appears to promote retraction of the injured
vessel.
 Both the above actions contribute to haemostasis.

17. CONT;
Raynaud’s phenomenon:
 Release of 5-HT from platelets may trigger acute vasospastic episodes of larger
arteries.
Variant angina:
 Along with thromboxane A2, 5-HT released from platelets has been implicated in
causing coronary spasm and variant angina.
Intestinal motility:
 Enterochromaffin cells and 5-HT containing neurones may regulate peristalsis
and local reflexes in the gut.