Role of serendipity in the discovery of classical antidepressant drugs: Applying operational criteria and patterns of discovery

Table 1 Classification of classical monoaminergic antidepressants according to action mechanism and historical perspective on their clinical introduction

Family	Mechanisms of action	Acronym	Prototype substance	Period
Tricyclic antidepressants	5-HT and NA reuptake inhibitors with blocking action of diverse receptors	TCA	Imipramine	1957-1980
Monoamine oxidase inhibitors	Irreversible MAO inhibitors	MAOI	Phenelzine	1958-1965
Heterocyclic or “second generation” antidepressants	NA reuptake inhibitors with blocking action of diverse receptors		Maprotiline	1967-1980
	Antagonists of α2 auto-receptors		Mianserin	1970-1980
	DA and NA reuptake inhibitors		Nomifensine	1970-1980
	5-HT reuptake inhibitor and antagonist of 5-HT2 receptors		Trazodone	1970-1980

5-HT: Serotonin; NA: Norepinephrine; DA: Dopamine; TCAs: Tricyclic antidepressants; MAOIs: Monoamine oxidase inhibitors.