MK 0777 is a selective GABAA α2/3 receptor partial agonist, for potential use in the treatment of Schizophrenia, Anxiety Disorder, and Generalized Anxiety Disorder. MK-0777 is functionally selective for the α2 and α3 subunits, with virtually no activity for the α1 and α5 subunits. Therefore, MK-0777 cause less sedation, interact less with alcohol, and exhibit less abuse potential and physical dependence than benzodiazepines. Unfortunately, in clinical trials, MK-0777 has little benefit for cognitive impairments in people with schizophrenia and anxiety disorder.

Meclinertant (SR-48692) is the first non-peptide antagonist of neurotensin receptors. It is potent and selective vs the high-affinity binding sites and with a small activity on the levocabastine-sensitive binding sites. It is active on several species including man without partial agonist properties. In vivo, it is active by oral route with a long duration of action and it is able to cross the blood-brain barrier. Meclinertant may be considered a powerful tool for investigating the role of neurotensin in physiological and pathological processes. Meclinertant has been developing for the treatment of anorexia nervosa; colorectal cancer; irritable bowel syndrome; pain; pancreatic cancer; prostate cancer; schizophrenia; small cell lung cancer however its development was discontinued.

Eclanamine is a nontricyclic antidepressant agent. Down-regulation of beta-adrenergic receptors in the cerebral cortex may be involved in mediating the eclanamine pharmacological effect.

Ecopipam (SCH-39166) is a selective D1 dopamine receptor antagonist both in vitro and in vivo. Additionally, it exhibits saturable, high-affinity binding to D5 receptors. Ecopipam was studied clinically for a variety of indications, including schizophrenia, drug abuse, and obesity, but in each case undesirable effects were observed. Currently, ecopipam is in clinical trials for the treatment of Lesch-Nyhan and Gilles de la Tourette's syndromes.

Cytochlor is a radio-sensitizing pyrimidine nucleoside with potential antineoplastic activity. Cytochlor is metabolized first to a phosphate derivative, CldCMP, by the enzyme deoxycytidine kinase and then to the active uracyl derivative, CldUMP, by the enzyme dCMP deaminase. CldUMP, the active metabolite, incorporates into DNA and, upon exposure to radiation, induces the formation of uracil radicals and double-strand DNA breaks. Cytochlor has been used in trials studying the treatment of Head and Neck Cancer and Brain and Central Nervous System Tumors.

Eltanolone (pregnanolone) is an endogenous neuro active steroid that is biosynthesized from progesterone. It is a positive allosteric modulator of the GABAA receptor, as well as a negative allosteric modulator of the glycine receptor. There is strong evidence that it is involved in the pathophysiology of premenstrual syndrome, catamenial epilepsy, major depression, and stress-sensitive brain disorders and is known to have sedative, anxiolytic, anesthetic, and anticonvulsant effects. It was investigated for clinical use as a general (intravenous) anesthetic. It produced unwanted side effects such as convulsions on occasion, and for that reason was not marketed. Pregnanolone possesses neuroprotective and neurotrophic properties thus has been through a number of clinical trials including for treatment of traumatic brain injury (TBI), Alzheimer disease, cognitive impairment and fragile X-associated tremor/ataxia syndrome.

Halopemide is a new psychotropic agent, a structural analog of the neuroleptics of the butyrophenone type but with different pharmacological and clinical properties. Preliminary clinical findings indicate that halopemide lacks the ability to induce parkinsonism and may be an effective drug in the treatment of psychosis characterized by autism, emotional withdrawal or apathy. However, the results from of the double-blind study showed no significant difference between the placebo phase and halopemide phase. Halopemide is phospholipase D2 inhibitor: PLD1 and PLD2. Halopemide may be used as a screen to identify inhibitors of human PLD2 using an in vitro biochemical assay. It is also inhibitory at benzodiazepine binding sites.

IPSAPIRONE, an azapirone derivative structurally unrelated to the benzodiazepines, is a selective 5-HT1A serotonin receptor agonist. It has antidepressant and anxiolytic effects. IPSAPIRONE was studied in several clinical trials for depression and generalized anxiety disorder.

Apan (PPI-1019) is the lead compound of a series of β-amyloid-derived peptides designed by Praecis Pharmaceuticals in the US to interact with β-amyloid peptide, facilitating its clearance. Apan is derived from the D-enantiomeric Cholyl-LVFFA-NH2. Apan is developed by Praecis Pharmaceuticals to treat Alzheimer's Disease. Apan inhibits the aggregation of beta-amyloid and its associated nerve cell toxicity. In addition, Apan reaches the brain in quantities that are sufficient to block the aggregation of beta-amyloid molecules and alter the course of the disease. PPI-1019 completed phase I and II clinical trials and was found to be safe, well tolerated and amenable to cross bbb. After peptide administration, levels of Aβ1-40 in the CSF increased, which might be discussed as a sign for Aβ clearance out of the brain. PI-1019 had been in phase I/II clinical trials by Praecis Pharmaceuticals (acquired by GlaxoSmithKline in 2007) for the treatment of Alzheimer's disease(AD). However, this study had been discontinued.

Isamoltan (CGP 361A) is a β-adrenoceptor and serotonin 1B receptor antagonist. Isamoltane has reported activity as an anxiolytic in man. Isamoltan had been in phase III clinical trials for the treatment of anxiety. However, this research has been discontinued.