Hydroxytreptamine (Serotonin)

It is widely distributed in plants and animals. Highest concentration in mammals is found in the
pineal gland, acting as a precursor for melatonin. It is synthesized from the amino acid
tryptophan and acts on several types of receptors.
Pharmacolocial Actions:
5-HT causes constriction of renal, splanchnic, meningeal, and pulmonary arteries and veins and
venules, but dilatation of the blood vessels of skeletal musles, coronaries, and skin capillaries. It
has weak direct ino-chronotropic effect on the myocardium. It also stimulates smooth muscles,
especially of the intestines. Serotonin is widely distributed in the CNS, serving as a
neurotransmitter. Altered functions may be responsible for disturbances in sleep, mood, sexual
behavior, motor activity, pain perception, migraine, temperature regulation, endocrine control,
psychiatric disorders and extra-pyramidal activity.
Serotonin Agonists:
Sumatriptan is a selective agonist of 5-HT1 receptors and is highly effective in treating acute
attacks of migraine, but is not useful in the prevention. It relieves the nausea and vomiting, but
the headache may recur, necessitating repeated administrations.
It is administered orally or by the subcutaneous route. The bioavailability of oral dose is only 14
%; thus, the oral dose is several times larger than the subcutaneous dose.
Adverse effects include flushing and heat at the injection site, neck pain, dizziness, and tingling
of the hands.
The drug is contraindicated with symptomatic ischemic heart diseases, angina, and
hypertension as it may cause coronary vasoconstriction.
Buspirone, another serotonin agonist, is a useful effective anxiolytic agent.

Serotonin Antagonists:
a. Methysergide: blocks the actions of 5-HT on a variety of smooth muscles. It also has a
weak direct vasoconstrictor effect. It is an effective prophylactic agent for migrainous
headaches. But has no effect in treating acute attacks, even may worsen the condition.
Adverse reactions include gastrointestinal irritation, drowsiness, vertigo, and psychic
disturbances.
b. Cyproheptadine: is a potent antagonist of 5-HT and to a smaller extent of histamine and
acetylcholine. It stimulates appetite probably by acting directly on the hypothalamus. It can
block the release of hydrocortisone, and the production of aldosterone. It is mainly used to
relieve the itching associated with skin disorders such as allergic dermatitis. The common
adverse reaction is drowsiness.
c. Ondansetron: is specific 5-HT3 receptor antagonist. Given orally or intravenously, it is
useful in the management of nausea and vomiting associated with cytotoxic therapy.
Adverse reactions include headache, constipation, and allergic reactions.
d. Prochlorperazine and haloperidol have anti-5-HT activity and are sometimes used for
resistant acute attacks.