Iproniazid is a non-selective, irreversible monoamine oxidase inhibitor (MAO) of the hydrazine class. It was originally developed for the treatment of Tuberculosis, but in 1952, its antidepressant properties were discovered when researchers noted that patients given isoniazid became inappropriately happy. Iproniazid is no longer clinically prescribed and has been withdrawn due to incidences of hepatotoxicity.

Bifemelane is a psychotropic drug, was found to inhibit monoamine oxidase (MAO). It inhibited type A MAO (MAO-A) competitively and type B (MAO-B) noncompetitively and it was a more potent inhibitor of MAO-A than of MAO-B. Bifemelane is an antidepressant and cerebral activator that is used in Japan for the treatment of cerebral infarction patients with depressive symptoms, and in the treatment of senile dementia as well. It also appears to be useful in the treatment of glaucoma.

Lofepramine is a tricyclic antidepressant that is structurally similar to imipramine and is extensively metabolised to desipramine. In the absence of other major pharmacological effects it appears that its antidepressant activity stems from the facilitation of noradrenergic neurotransmission by uptake inhibition, and possibly by the additional facilitation of serotoninergic neurotransmission. The overall therapeutic efficacy of lofepramine is comparable to that of imipramine, amitriptyline, clomipramine, maprotiline and mianserin in patients with depression of varying severity, and coexisting anxiety. Lofepramine is a strong inhibitor of norepinephrine reuptake (Ki=5.4 nM) and a moderate inhibitor of serotonin reuptake (Ki=70 nM). It is a weak-intermediate level antagonist of the muscarinic acetylcholine receptors.Lofepramine is licensed for the treatment of depression in the United Kingdom.

Iproclozide [1-(p-chlorophenoxyacetyl)-2-isopropylhydrazine] is a non-selective monoamine oxidase inhibitor. It has been used in the treatment of depressive states. Iproclozide was studied in the treatment of hypertension and angina pectoris. It may induce fatal hepatitis.

Etoperidone is an atypical antidepressant introduced in Europe in 1977. The activity of etoperidone is made mainly by its major metabolite 1-(3'-chlorophenyl)piperazine (mCPP). mCPP binds with different affinity to most of the serotonergic receptors and adrenergic receptors. This metabolite is an agonist of 5-HT2c and an antagonist of 5-HT2a. Part of etoperidone structure contributes to the activity in the α-adrenergic receptors. Etoperidone has been studied for the treatment of depression, tremors in Parkinson, extrapyramidal symptoms and male impotence. It is not certain if it was ever approved and marketed but its current status is withdrawn.

TIANEPTINE, a tricyclic antidepressant, is a drug used for the treatment of the major depressive disorder. It was discovered by The French Society of Medical Research in the 1980s. Unlike other tricyclic antidepressants, TIANEPTINE is a selective serotonin reuptake enhancer with minimal effects on norepinephrine and dopamine uptake. Also, it is a full agonist at the mu-opioid and delta-opioid receptors with no effect at the kappa-opioid receptors. Selective mu-opioid agonists typically induce euphoria, which may contribute to TIANEPTINE's antidepressant effect. It is marketed as Coaxil/Stablon in many European countries, but it is not available in the US.

Imipraminoxide (brand names Imiprex, Elepsin) is a tricyclic antidepressant and imipramine metabolite that was used in Europe for the treatment of depression. In comparison with the imipramine, Imipraminoxide efficacy was identical to imipramine. However, in clinical trials, imipraminoxide was found to have a faster onset of action, and fewer and less marked side effects, including diminished orthostatic hypotension and anticholinergic effects like dry mouth, sweating, dizziness, and fatigue. Imipraminoxide's pharmacology has not been well elucidated, but based on its very close relationship with imipramine, it likely acts as a serotonin and norepinephrine reuptake inhibitor and serotonin, adrenaline, histamine, and muscarinic acetylcholine receptor antagonist, though with weaker antiadrenergic and anticholinergic actions

Iprindole under the brand name Prondol was used as an antidepressant but now is no longer marketed. It possesses the beta-adrenergic properties and has an indirect beta 2-mimetic effect.

Oxaflozane is non-tricyclic antidepressant with serotoninergic action. In animals, oxaflozane has anti-cataleptic and anti-aggressive action with weak potentiation of stereotypes provoked by amphetamine. Oxaflozane was developed by Solvay Pharma and marketed in France under tradename Conflictan. The drug was discontinued in 2004.

Quinupramine is a tricyclic antidepressant used in the treatment of reactive and endogenous depression. Quinupramine was found to possess a higher affinity for muscarinic cholinergic receptor binding sites in brain and heart, compared with imipramine. Quinupramine also displayed a substantial affinity for 5-HT2 receptors in the cerebral cortex. Quinupramine may show many adverse side effects such as dry mouth, urinary retention, and daytime drowsiness.