Tetracyclic

Tetracyclic is a term used in chemistry and pharmacology to describe molecules that contain four fused rings in their core structure. In pharmacology it is most commonly applied to a subclass of antidepressants known as tetracyclic antidepressants, which are structurally related to tricyclic antidepressants but feature an additional ring in the core system.

The tetracyclic framework can influence the drugs’ receptor binding and pharmacological profiles, giving these agents distinctive effects compared with older tricyclics. While they share some mechanisms with tricyclics, tetracyclic antidepressants often exhibit different receptor activities that contribute to their clinical actions and side-effect profiles.

Examples of tetracyclic antidepressants commonly cited include mianserin and mirtazapine. Some sources also describe maprotiline as tetracyclic, depending on the classification used. The exact mechanism of action varies by compound: mianserin and mirtazapine typically act as antagonists at central alpha-2 adrenergic receptors, which increases release of norepinephrine and serotonin; they can also block certain serotonin receptors (such as 5-HT2 and 5-HT3 in some cases) and interact with histamine receptors, contributing to sedative and antidepressant effects.

In clinical use, tetracyclic antidepressants were developed in the mid-20th century and provided alternatives to first-generation tricyclics. They are less commonly prescribed today, having been largely supplanted by selective serotonin reuptake inhibitors and other newer antidepressants, but they remain options for certain patients, such as those who require sedation, have specific symptom profiles, or do not respond to other treatments.

The term contrasts with tricyclic antidepressants in both structure and pharmacology, reflecting the broader diversity of four-ring systems within the antidepressant landscape.