Trifluoperazine (Eskazinyl, Eskazine, Jatroneural, Modalina, Stelazine, Terfluzine, Trifluoperaz, Triftazin) is a typical antipsychotic of the phenothiazine chemical class used for the short-term treatment of certain types of anxiety. Trifluoperazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis. The primary application of trifluoperazine is for schizophrenia. Other official indications may vary country by country, but generally, it is also indicated for use in agitation and patients with behavioral problems, severe nausea, and vomiting as well as severe anxiety. Trials have shown a moderate benefit of this drug in patients with borderline personality disorder. A 2004 meta-analysis of the studies on trifluoperazine found that it is more likely than placebo to cause extrapyramidal side effects such as akathisia, dystonia, and Parkinsonism. It is also more likely to cause somnolence and anticholinergic side effects such as red-eye and xerostomia (dry mouth).

Perphenazine is a relatively high potency phenothiazine that blocks dopamine 2 receptors predominantly, but also may possess antagonist actions at histamine 1 and cholinergic M1 and alpha 1 adrenergic receptors in the vomiting center leading to reduced nausea and vomiting. The drug was approved by FDA for the treatment of schizophrenia and control of severe nausea and vomiting (either alone or in combination with amitriptyline hydrochloride). Perphenazine is extensively hepatic to metabolites via sulfoxidation, hydroxylation, dealkylation, and glucuronidation; primarily metabolized by CYP2D6 to N-dealkylated perphenazine, perphenazine sulfoxide, and 7-hydroxyperphenazine (active metabolite with 70% of the activity of perphenazine) and excreted in the urine and feces.

Chlorpromazine is a psychotropic agent indicated for the treatment of schizophrenia. It also exerts sedative and antiemetic activity. Chlorpromazine has actions at all levels of the central nervous system-primarily at subcortical levels-as well as on multiple organ systems. Chlorpromazine has strong antiadrenergic and weaker peripheral anticholinergic activity; ganglionic blocking action is relatively slight. It also possesses slight antihistaminic and antiserotonin activity. Chlorpromazine acts as an antagonist (blocking agent) on different postsysnaptic receptors -on dopaminergic-receptors (subtypes D1, D2, D3 and D4 - different antipsychotic properties on productive and unproductive symptoms), on serotonergic-receptors (5-HT1 and 5-HT2, with anxiolytic, antidepressive and antiaggressive properties as well as an attenuation of extrapypramidal side-effects, but also leading to weight gain, fall in blood pressure, sedation and ejaculation difficulties), on histaminergic-receptors (H1-receptors, sedation, antiemesis, vertigo, fall in blood pressure and weight gain), alpha1/alpha2-receptors (antisympathomimetic properties, lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction, but may also attenuate pseudoparkinsonism - controversial) and finally on muscarinic (cholinergic) M1/M2-receptors (causing anticholinergic symptoms like dry mouth, blurred vision, obstipation, difficulty/inability to urinate, sinus tachycardia, ECG-changes and loss of memory, but the anticholinergic action may attenuate extrapyramidal side-effects). Additionally, Chlorpromazine is a weak presynaptic inhibitor of Dopamine reuptake, which may lead to (mild) antidepressive and antiparkinsonian effects. Chlorpromazine has being marketed under the trade names Thorazine and Largactil among others. Chlorpromazine is used for treating certain mental or mood disorders (eg, schizophrenia), the manic phase of manic-depressive disorder, anxiety and restlessness before surgery, the blood disease porphyria, severe behavioral and conduct disorders in children, nausea and vomiting, and severe hiccups.

Apomorphine (brand names: Apokyn, Ixense, Spontane, Uprima) is indicated for the acute, intermittent treatment of hypomobility, “off” episodes (“end-of-dose wearing off” and unpredictable “on/off” episodes) in patients with advanced Parkinson’s disease. Apomorphine has been studied as an adjunct to other medications. It is a non-ergoline dopamine agonist with high in vitro binding affinity for the dopamine D4 receptor, and moderate affinity for the dopamine D2, D3, and D5, and adrenergic α1D, α2B, α2C receptors. The precise mechanism of action as a treatment for Parkinson’s disease is unknown, although it is believed to be due to stimulation of post-synaptic dopamine D2-type receptors within the caudate-putamen in the brain.

TIC10 (TIC10 isomer or ONC201 isomer) is a potent, orally active, and stable small molecule and is an efficacious antitumor therapeutic agent that acts on tumor cells and their microenvironment to enhance the concentrations of the endogenous tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). The isomeric structure of TIC10/ONC201 is critical to its activity: anti-cancer activity is associated with the angular structure and not the linear TIC10 isomer. TIC10 transcriptionally induces a sustained up-regulation TRAIL in tumors and normal cells in a p53-independent manner. TIC10 inactivates kinases Akt and extracellular signal-regulated kinase (ERK), leading to the translocation of Foxo3a into the nucleus, where it binds to the TRAIL promoter to up-regulate gene transcription. TIC10 crosses the blood-brain barrier. TIC10 treatment caused tumor regression in the HCT116 p53−/− xenograft, RKO human colon cancer xenograft–bearing mice and human triple-negative breast cancer xenografts and significantly prolonged the survival of Eμ-myc transgenic mice, which spontaneously develop metastatic lymphoma from weeks 9 to 12 of age by 4 weeks.

Sunepitron (CP-93,393) is an anxiolytic drug with highly selective serotonin 5-hydroxytryptamine 1A autoreceptor agonist, alpha2-adrenergic antagonist, and dopamine D2 agonist properties. Sunepitron hydrochloride had been in Phase III clinical trials by Pfizer for the treatment of anxiety disorder and depression. However, this research has been discontinued.

Nepicastat (SYN-117) is a potent and selective inhibitor of dopamine-β-hydroxylase. This compound in Phase 2 of clinical trial for the treatment cocaine addiction and posttraumatic stress disorder.