ANTIDEPRESSANT AGENTS

Depression is one of the most common psychic disorders. Antidepressants are the drugs which
are mainly used in the management of depression.
Types of antidepressant drugs

Atypical antidepressants
Pharmacokinetics
Most tricyclics are incompletely absorbed and undergo significant first-pass metabolism. Highly
protein bound and relatively high lipid solubility. Fluoxetine (Selective Serotonin Reuptake
Inhibitors (SSRIs)) is well absorbed. The MAO inhibitors are readily absorbed from the
gastrointestinal tract.
Mechanisms of action
Tricyclic antidepressanat (imipramine, amitriptyline) closely related in structure to
phenothiazines are the most widely used antidepressants. TCAs block the uptake of amines
(noradrenaline and 5-HT) by nerve terminals by competition for the carrier transport system. In
addition, TCAs block α1- adrenoceptors, muscarinic, histamine (H1) and 5-HT receptors.
Monoamine oxidase inhibitors (MAOI): Tranylcypromine selectively inhibits MAO-A. MAO-A has
a substrate preference for 5 –HT. MAOI causes a rapid and sustained increase in the 5-HT,
noradrenaline and dopamine.
Selective 5-HT uptake inhibitors: fluoxetine, fluvoxamine lack antimuscarinic and cardiovascular
effects.
Atypical antidepressant drugs have no common mechanisms of action, some are monoamine
uptake blockers, but others act by unknown mechanisms.
Clinical Indications: The major indication of TCAs are endogenous depression, panic attacks,
Phobic and obsessional states (clomipramine) and bed-wetting in children. MAOIs are used in
severe depression refractory to other treatment and phobias.

Adverse Effects: Postural hypotension, dry mouth, blurred vision, constipation, urine retention,
sedation, are the most important side effects of TCAs. MAOI cause postural hypotension,
atropine-like effects, weight gain, and CNS stimulation causing restlessness, tremor, and
insomnia.
TCA and MAO inhibitors cause atropine like effects and postural hypotension. MAOI cause
excessive central stimulation and weight gain.

Tricyclic antidepressants (TCAs)

Monoamine oxidase inhibitors (MAOI)

5-HT uptake inhibitors