Tricyclics

Amitriptyline, nortriptyline, imipramine, clomipramine, doxepin, desipramine. They inhibit serotonin and noradrenaline reuptake like the later classes and then keep going — H1, muscarinic and α₁ antagonism as well, which is where the sedation, the dry mouth, the urinary retention and the postural hypotension come from. The tertiary amines are the more serotonergic and more antimuscarinic; the secondary amines lean noradrenergic and are somewhat cleaner.

The class-level fact is overdose. Tricyclics block cardiac sodium channels, so an overdose is a cardiac and seizure emergency rather than a serotonergic one, and the gap between a treatment dose and a dangerous one is far narrower than in the classes built to replace them. Their antimuscarinic load also adds to the deliriants and the first-generation antihistamines, and their sedation adds to everything sedating.