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

1. Tricyclic antidepressants (TCAs)
2. Monoamine oxidase inhibitors (MAOI)
3. 5-HT uptake inhibitors
4. 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 a_1- 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.