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.

Bifeprunox, code name DU-127,090 is an atypical antipsychotic agent, which combines minimal D2 receptor agonism with 5-HT receptor agonism. Bifeprunox was in phase III of clinical trials for the treatment of schizophrenia, Bipolar Depression and in phase I for Parkinson's disease, but these studies were discontinued because efficacy data did not support pursuing the existing development strategy of stabilization of non-acute patients with schizophrenia.

Pozanicline is an alpha4-beta2 neuronal nicotinic receptor partial agonist. It had been in phase II clinical trials for the treatment of attention hyperactivity disorder and Alzheimer’s disease. It was tested for the treatment of schizophrenia too. All these studies were discontinued. Modulation of hippocampal learning and memory using Pozanicline in animal model was effective as novel therapeutic strategies for nicotine addiction. However future clinical trial was terminated.

Aplindore (DAB-452) is a small molecule that displays potent dopamine D2 receptor partial agonist activity in in vitro and in vivo assays and is predicted to have antipsychotic efficacy without motor side effects. Aplindore had been in phase II clinical trials for the treatment of Parkinson's disease and restless legs syndrome. Aplindore was generally well tolerated and there were no withdrawals due to adverse events and no serious adverse events.

Pipequaline (PK-8165, 2-phenyl-4[2-(4-piperidinyl) ethyl]quinoline) is a benzodiazepine receptor partial agonist.

Alvameline is a partial agonist of the M1 mAChR that also displays M2/M3 antagonist effects. It readily crosses the blood-brain barrier. It has an effect profile that makes it of interest to test its ability to counteract bladder overactivity in humans. Behaviorally, alvameline has been shown to significantly improve Morris water maze (MWM) performance in both young and ageimpaired rats. It failed to improve cognition in patients with mild to moderate Alzheimer's disease.

Eltoprazine, a 5-HT1A/B receptor partial agonist, was created by Duphar in the 1980s (as DU-28853) and was subsequently developed by Solvay to treat pathological aggression. This drug is in clinical development for the treatment of Parkinson's disease levodopa-induced dyskinesia (PD-LID), Alzheimer's aggression and adult attention deficit hyperactivity disorder (adult ADHD). In addition, was shown, that the drug could be useful for normalizing prefrontal cognitive abilities, reducing aggression and impulsivity, and improving cognitive function in schizophrenia.

FLESINOXAN, a phenylpiperazine derivative, is a selective agonist for 5-HT1A receptors. It is an antidepressant agent which clinical development was stopped.

Droloxifene, a derivative of the triphenylethylene drug tamoxifen, is a novel selective estrogen receptor modulator (SERM). Droloxifene also exhibits more rapid pharmacokinetics, reaching peak concentrations and being eliminated much more rapidly than tamoxifen. Its higher affinity to the estrogen receptor, higher anti-estrogenic to estrogenic ratio, more effective inhibition of cell growth and division in estrogen receptor-positive cell lines, and lower toxicity give it theoretical advantages over tamoxifen in the treatment of human breast cancer. Short-term toxicity was generally mild, and similar to that seen with other antiestrogens. Droloxifene appears active and tolerable. It may have a particular role in situations in which rapid pharmacokinetics, or an increased antiestrogenic to estrogenic ratio, are required. Droloxifene may also be a potentially useful agent for the treatment of postmenopausal osteoporosis because it can prevent estrogen deficiency-induced bone loss without causing uterine hypertrophy. Droloxifene may have an effect on bone and breast tissue because it induces apoptosis. Droloxifene has an anti-implantation effect in rats, and the effect appears to be not completely due to its anti-estrogenic activity.

Tiospirone (TSP) is an atypical antipsychotic drug. Tiaspirone appeared to be a promising antipsychotic agent as it didn`t cause extrapyramidal syndromes. It has 5HT-2 antagonistic properties as well as affinity for D2, 5HT-1a, 5HT-6 and sigma receptors. Tiospirone was in phase III clinical trials for the treatment of attention hyperactivity disorder with Mead Johnson in the USA but its development appears to have been discontinued.