Dibenzepin is a tricyclic antidepressant of the dibenzo-epine group. It is a selective noradrenaline uptake inhibitor, which exhibits in vitro and in vivo imipramine-like effects. It binds strongly to histamine H1 receptors in the brain and, to a lesser extent, to cholinergic receptors. The pharmacological profile of dibenzepin corresponds widely to its biochemical properties: histamine antagonism, tetrabenazine antagonism, potentiation of various noradrenergic effects and anticholinergic effects. Dibenzepin is only available in European countries for the treatment of depression.

Toloxatone is an antidepressant launched in 1984 in France for the treatment of depression. It is a selective reversible inhibitor of MAO-A (RIMA).

Amineptine is a selective inhibitor of dopamine reuptake. The drug was developed in France and was marketed for the treatment of depressive disorders under the name Survector among the others. Amineptine was withdrawn from the French market in 1999 because of abuse and drug dependence and because of its hepatic (cholestatic injuries) and cutaneous (acne) adverse effects.

Butriptyline is a tricyclic antidepressant used in patients with depression associated with anxiety. The drug is supposed to be withdrawn from the market as the last publication about its clinical use is dated by 1988.

Agomelatine behaves both as a potent agonist at melatonin MT1 and MT2 receptors and as a neutral antagonist at 5-HT2C receptors. Accumulating evidence in a broad range of experimental procedures supports the notion that the psychotropic effects of agomelatine are due to the synergy between its melatonergic and 5-hydroxytryptaminergic effects. Agomelatine is indicated for the treatment of major depressive episodes.

Reboxetine is a selective noradrenergic reuptake inhibitor that acts by binding to the norepinephrine (NE) transporter and blocking reuptake of extracellular NE back into terminals. This compound has low affinity for other transporters and receptors. Reboxetine is used in acute treatment of depressive illness / major depression. Very common side effects are: difficulties to sleep (insomnia); dizziness; dry mouth; constipation; nausea (feeling sick); sweating. Based on studies conducted primarily outside the US, the FDA granted a preliminary letter of approval in 1999. However, more recent clinical studies conducted in the US and Canada, prompted by the FDA, resulted in a letter of non-approval.

cis-Dosulepin is a stereoisomer of Dothiepin (trade name Prothiaden, Dothep, Thaden, and Dopress; Dosulepin (INN, BAN) a tricyclic antidepressant that is used in several European and South Asian countries, as well as Australia, South Africa, and New Zealand. Dosulepin is used for the treatment of the major depressive disorder and neuropathic pain. Dosulepin is only Therapeutic Goods Administration and Medicines and Healthcare products Regulatory Agency approved for the treatment of the major depressive disorder. Dothiepin is not used in the United States. The central action of cis-dosulepin was compared with that of its antidepressant stereoisomer trans-dosulepin, cis-dosulepin exerted weaker anti-reserpine, anti-tetrabenazine, and 3H-5-HT (serotonin) uptake inhibiting actions than trans-dosulepin, but cis-dosulepin's inhibition of 3H-dopamine and 3H-norepinephrine uptake was slightly more potent than that of trans-dosulepin. On the other hand, cis-dosulepin exhibited extremely potent anticholinergic action in oxotremorine induced tremor, isolated ileum and the 3H-quinuclidinyl benzilate binding test. It also showed potent apomorphine enhancing the action and shortened the period of immobility in the forced swimming test in animals.

Minaprine, a psychotropic drug, which was effective in the treatment of various depressive states. This drug was withdrawn because of the serious side effect. It was found, that minaprine inhibited the following enzymes, acetylcholinesterase and monoamine oxidase (MOA) A. It also binds to dopamine D1 and D2 receptors. Experiments on rodents also have revealed that minaprine suppressed the inhibitory effect of hydroxytryptamine (5-HT) on dopamine (DA) release via the inhibition of 5-HT binding at the 5-HT2 receptor on the nerve terminal.

Pivagabine [4-(2,2-dimethyl-1-oxopropylamino) butanoic acid] is a hydrophobic 4-aminobutyric acid derivative with neuromodulatory activity. Pharmacokinetic and toxicological evaluations showed that pivagabine penetrates the blood-brain barrier in rats, does not undergo metabolic transformation and exhibits a low toxicity after either single or repeated administration. Moreover, behavioral studies demonstrated that this compound prevented pentylenetetrazol- and bicuculline-induced convulsions in rats. Pivagabine was shown to improve performance on stress-related tests by reducing the anxiety-producing reactions to the various experimental settings. The marked antistress action of Pivagabine is mediated by antagonizing the effects of stress on GABA(A) receptor function and corticotropin-releasing factor concentrations in the brain, but not by altering the stress-induced increase in neurosteroid concentrations. Pivagabine treatment reduced the physical and mental fatigability of neurasthenia patients and increased their sense of well-being.

Opipramol (Insidon, Pramolan, Ensidon, Oprimol) is an antidepressant and anxiolytic used in Germany and other European countries. Although it is a member of the tricyclic antidepressants, opipramol's primary mechanism of action is much different in comparison, it doesn’t represent a tricyclic antidepressant drug as it does not inhibit the neuronal uptake of norepinephrine and/or serotonin. Opipramol also acts as a low to moderate affinity antagonist for the D2, 5-HT2, H1, H2, and muscarinic acetylcholine receptors. H1 and H2 receptor antagonism account for its antihistamine effects, and muscarinic acetylcholine receptor antagonism is responsible for its anticholinergic properties. Opipramol was developed by Schindler and Blattner in 1961. Opipramol is typically used in the treatment of generalized anxiety disorder (GAD) and somatoform disorders. Its anxiolysis becomes prominent after only one to two weeks of chronic administration. Upon first commencing treatment, opipramol is rather sedating in nature due to its antihistamine properties, but this effect becomes less prominent with time. The therapy with Opipramol indicates an additional therapy with neuroleptics, hypnotics and tranquilizers (e.g. Barbiturates, Benzodiazepines). Therefore, it should be noted that some specific reactions, particularly CNS depressant effects could be intensified and an intensification of common side effects may occur. If necessary the dosage may be reduced. Co-administration with alcohol can cause stupor. MAO Inhibitors should be discontinued at least 14 days before the treatment with Opipramol. Concomitant use of Opipramol with β-blockers, antiarrhythmics (of class 1c), as well as drugs from tricyclic antidepressant group and preparations which influence the microsomal enzyme system, can lead to change in plasma concentration of these drugs. Co-administration of neuroleptics (example- haloperidol, risperidone) can increase the plasma concentration.