tricyclic

Tricyclic describes chemical compounds that contain three fused or annulated rings in their core structure. The term is most commonly encountered in pharmacology in reference to tricyclic antidepressants (TCAs), a class of drugs developed in the mid-20th century for mood disorders. More broadly, tricyclic compounds include any molecule with three interconnected ring systems, which may be fully fused or linked in other arrangements, including certain heterocyclic and polycyclic aromatics.

A typical tricyclic antidepressant features a compact three-ring core often modifiable by substitutions that influence lipophilicity, receptor affinity, and monoamine transporter blockade. Classic examples are imipramine, amitriptyline, nortriptyline, desipramine, and clomipramine. The tricyclic framework also appears in other drug classes, such as certain phenothiazines, which share a three-ring core and have been used as antipsychotics, though not all tricyclics have identical pharmacological profiles.

Mechanism of action for TCAs generally involves inhibition of the reuptake transporters for norepinephrine and serotonin, increasing their synaptic concentrations. Additional receptor antagonism—including histamine H1, alpha-adrenergic, and muscarinic acetylcholine receptors—contributes to pharmacological effects and to a range of adverse effects. The broad activity can lead to significant anticholinergic, sedative, and cardiovascular risks, especially in overdose.

Today, TCAs have largely been supplanted by selective serotonin–norepinephrine reuptake inhibitors (SNRIs) and SSRIs for depression, but they remain in use for certain conditions and in patients who do not respond to newer agents.