(Mode of Action of Drugs)

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Chapter

1.4

Chapter

5.2 Serotonin and its Antagonists

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Serotonin and its

Antagonists

5-HYDROXYTRYPTAMINE (5-HT, SEROTONIN)

5-Hydroxytryptamine is widely distributed
in plant and animal tissues, mast cells,
platelets, the enterochromaffin cells located
throughout the gastrointestinal tract, and
in certain regions of the brain. It is also
present in the venoms and stings. Some
fruits such as bananas, pineapples,
tomatoes and plums contain considerable
amount of 5-HT.

It is an indole ethylamine formed in
biological systems from the amino acid L-
tryptophan by hydroxylation with
tryptophan hydroxylase enzyme, followed
by the decarboxylation by the nonspecific
aromatic L-amino acid decarboxylase. 5-HT
is then taken up into secretory granules and
stored.

Pharmacological Actions

Cardiovascular system: 5-HT can
directly stimulate or relax smooth muscles
via 5-HT 1 & 5-HT 2 receptors and can
influence the release of noradrenaline from
adrenergic nerves and stimulate endothelial
cells to release EDRF and prostaglandins. It

acts directly to constrict the arteries and

increases the peripheral vascular resistance.

The released adrenaline from adrenal

medulla, affects ganglionic transmission and

evokes cardiovascular reflexes.

On heart, 5-HT has weakly direct

positive inotropic and chronotropic effects,

that are mediated by 5-HT 1 receptors. 5-HT 3

receptors are also present on vagal nerve

endings in the coronary bed, which evoke

bradycardia and hypotension.

A characteristic ‘triphasic response’ is

observed after intravenous injection. The

early transient fall in blood pressure is due

to stimulation of chemoreceptors. The

second phase, pressor effect is due to

vasoconstriction. The final depressor phase

is due to vasodilator action on the skeletal

muscle.

Smooth muscle: 5-HT stimulates

smooth muscles, it increases the motility of

the small intestine, stomach and also large

intestine by which peristalsis is increased &

diarrhoea can occur.

It also constricts bronchial smooth

muscles, but is less potent than histamine. It