Volinanserin (MDL-100,907) is a highly selective 5-HT2A receptor antagonist. It is widely used in scientific research to investigate the function of the 5-HT2A receptor. Volinanserin is also being trialed as a potential antipsychotic, antidepressant and treatment for insomnia. Volinanserin (M-100907) was in phase III trials for chronic schizophrenia. In August 1999, development was discontinued for acute schizophrenia (schizoaffective disorder) on the basis of poor results. M-100907 is also active in animal models involving blockade of NMDA glutamatergic channel receptors, an effect known to resemble some behavioral symptoms of schizophrenia in man. M-100907 is also claimed in other patents for the treatment of thromboembolic disorders, for the treatment of various developmental neurological disorders such as autism and attention deficit hyperactivity disorder.

Rosonabant (E-6776) is a CB1-receptor antagonist that has appetite suppressant activity and was under development for the treatment of obesity. This preclinical anti-obesity drug shows activity that is similar to romonabant, a drug that was withdrawn from the European market due to severe side effects such as nausea, depression and suicidal ideations. Drug development of rosonabant has subsequently been halted.

Minaxolone, a water-soluble steroid anesthetic that was studied in 1970s/1980s. It is a positive allosteric modulator of the GABAA receptor. This compound was withdrawn before registration due to reported toxicity in rats.

Metenkephalin (Met-enkephalin) is an endogenous opioid peptide that acts as an agonist at μ-opioid receptors (μORs) and δ-opioid receptors (δORs). Met-enkephalin exhibits neuromodulatory, antinociceptive/analgesic, antidepressant, and gastrointestinal motility modulating activities. Like other endogenous opioids, met-enkephalin modulates expression of opioid receptors and plays a role in reward/reinforcement signaling. Met-enkephalin is also involved in exercise-induced reversal of neuropathic pain and in animals undergoing the forced swim test, decreases immobility time. Met-enkephalin inhibits gastrointestinal muscle contractility, inhibiting motility and gastric emptying. Additionally, analogs of this peptide display anticancer and antiepileptic/anticonvulsant activities.

Moxazocine is a benzomorphan derivative patented by Bristol-Myers Co. as potent opioid analgesic. Moxazocine acts as a partial agonist or mixed agonist/antagonist of the opioid receptors and binds preferentially to the κ-opioid receptor. In clinical studies, Moxazocine demonstrated superior efficacy compared morphine, but was never marketed.

Lirequinil is a benzoquinolizinone derivative. It is a partial agonist to the benzodiazepine (BDZ) receptor. Lirequinil slightly lowered the rhythmic slow-wave activity frequency during waking mobility. Lirequinil acts more selectively than nitrazepam to promote the drowsy EEG pattern, and the partial agonistic properties may minimize the residual effects during waking mobility similar to the short-acting agent zopiclone. Lirequinil was well tolerated at all doses, causing no clinically relevant changes in vital signs or laboratory parameters. At doses of 10 and 30 mg there were signs of unsteady gait, indicating a central nervous system depressant effect. Lirequinil had been in phase II for the treatment of sleep disorders.

Dilopetine is a racemic mixture of (+)-E-6006 citrate (E-6101) and (-)-E6006 citrate (E-6102) enantiomers being developed as a potential antidepressant. Initial experiments indicate that dilopetine exhibits an antidepressant profile in tests with mice and rats. Dilopetine has been observed to normalize the increased substance P levels in the periaqueductal gray of rats during stressor exposure (Hamon, personal communication), suggesting that the drug may function by inhibiting substance P release. Treatment with dilopetine reduced the vocalizing of isolated guinea pig pups in a dose-dependent fashion.

Hexopyrronium is an antihistaminic agent. Its gastric antisecretory action was studied in human. Information about the current use of this drug is not available.

Conorphone (TR5109) is an opioid of mixed agonist-antagonist analgesic class. In animal models, conorphone demonstrated an analgesic activity in the same range as morphine, and lack of addiction liability. Conoprphone was evaluated in a clinical trial for postoperative pain in the oral surgery model and in patients with postepisiotomy pain. The 40 mg dose of conorphone resulted in a significant incidence of side effects such as drowsiness, dizziness, nausea, and vomiting.

Clovoxamine is an antidepressant and anxiolytic drug, acting as a serotonin and norepinephrine reuptake inhibitor. The drug was investigated in the double-blind clinical trials for the treatment of anxiety neurosis, where it was compared with diazepam, and found to have comparable efficacy but higher drop out rate.