CGP-36742 (3-Aminopropyl-n-butyl-phosphinic acid) is one of the first GABAB receptor antagonists that can penetrate the blood-brain barrier after peripheral administration. Although its affinity for GABA B binding sites labeled with a tritiated agonist is modest, being in the low micromolar range, it displays significant pharmacological activity when administered either orally or parenterally. CGP 36742 was effective in the learned helplessness paradigm in rats, dose-dependently improving the escape failures induced by the inescapable shocks, suggesting that it may have an antidepressant profile. CGP36742 displays pronounced cognition enhancing effects in Rhesus monkeys in active and passive avoidance paradigms, in an eight-arm radial maze and a Morris water maze and in a social learning task. CGP36742 blocks the late inhibitory postsynaptic potential and the paired-pulse inhibition of population spikes recorded from CA1 pyramidal neurons of the hippocampus of rats in vitro and in vivo. CGP36742 significantly enhances the release of glutamate, aspartate, glycine and somatostatin in vivo. Chronic administration of CGP36742 causes an up-regulation of GABA(B) receptors in the frontal cortex of rats. The effects of CGP36742 on cognition were investigated in a double-blind, placebo-controlled study undertaken as the first assessment of the efficacy of CGP36742 in 110 patients age 59–85 years with Mild cognitive impairment. The results showed significant improvement in working memory, psychomotor speed and attention with SGS742 as compared with placebo. SGS742 appeared to be safe and well tolerated in this study.

Setastine (Loderix) is a potent antagonist of histamine H1-receptor mediated responses. Setastine inhibits anaphylactic shock in guinea-pigs sensitized by horse serum. No antiserotonin, anticholinergic and antiadrenergic effect of the compound can be detected. Setastine has a long lasting (up to 16 h) antihistamine effect with a good oral effectiveness. It shows no cardiovascular effects in cats. Setastine shows a much weaker CNS depressant activity than clemestine fumarate. In displacement studies (3H-mepyramine) setastine had significantly weaker affinity for the central nervous system (CNS) H1-receptors than clemastine fumarate. It is concluded that setastine is a non-sedative highly active H1-antagonist.

Nelivaptan is a selective, orally active, non-peptide vasopressin receptor antagonist selective for the V1B subtype. It showed promise in preclinical animal models and advanced to phase II clinical trials for the treatment of anxiety and depression; however, in 2008, Sanofi-Aventis announced that further development of this drug had been halted.

Fenadiazole is a sedative/hypnotic drug. It has a a unique oxadiazole-based structure. It used to be manufactured by the French pharmaceutical company Laboratoires Jacques Logeais.

Sagopilone (BAY86-5302; ZK 219477; ZK-EPO) is a synthetic epothilone, an analog of patupilone that was developed by Bayer HealthCare as an anticancer agent. Epothilones are 16-member ring macrolides have demonstrated potent antiproliferative activity in several different multidrug-resistant and paclitaxel-resistant tumor cell lines in vitro and in vivo. Sagopilone binds to tubulin and induces microtubule polymerization, which may result in the induction of G2/M arrest, and apoptosis. Sagopilone is not a substrate for the P-glycoprotein efflux pump and so may exhibit activity in multidrug-resistant tumors. This drug was studied in clinical trials phase II in patients with recurrent ovarian cancer, in metastatic melanoma patients, for the treatment of advanced stage breast cancer and in the treatment of Glioblastoma patients. However, the development of this drug was discontinued, because of its adverse effects, including peripheral neuropathy.

Alvespimycin (17-desmethoxy-17-N,N-dimethylaminoethylamino-geldanamycin) (17-DMAG; NSC 707545) is an inhibitor of the molecular chaperone heat shock protein HSP90. Alvespimycin is a derivative of antineoplastic benzoquinone antibiotic geldanamycin. Alvespimycin binds to HSP90, a chaperone protein that aids in the assembly, maturation and folding of proteins. Subsequently, the function of Hsp90 is inhibited, leading to the degradation and depletion of its client proteins such as kinases and transcription factors involved with cell cycle regulation and signal transduction. Alvespimycin was studied in clinical trials for the treatment of solid tumors and hematologic malignancies however its development was discontinued.

Pirenperone, a quinazoline derivative, is a selective antagonist at serotonin receptor 2A binding sites. The liposoluble compound pirenperone has been studied in a variety of behavioral tests including the sensitive d-lysergic acid diethylamide (LSD) cue discrimination assay, in which it served as a potent LSD-antagonist. Pirenperone also proved to be an effective antagonist of serotonin-mediated behavioral responses including the head twitch response thought to be mediated by serotonin receptors.

Org 25935 (SCH 900435) is a synthetic drug developed by Organon International, which acts as a selective inhibitor of the glycine transporter GlyT-1. In human trial for prevention of relapse in alcohol-dependent patients in Org 25935 demonstrated no benefit over placebo in preventing alcohol relapse. Org 25935 was tested as an adjunctive treatment to atypical antipsychotics in predominant persistent negative symptoms of schizophrenia, where it did not differ significantly from placebo in reducing negative symptoms or improving cognitive functioning. Clinical trials against panic disorder did not show any benefit compared to placebo.

Quilostigmine (also known as NXX-066) is an isoquinolinecarboxylate patented by Hoechst-Roussel Pharmaceuticals Inc as a memory enhancer. Quilostigmine acts as acetylcholinesterase inhibitor and studies as a potential drug for treating Alzheimer’s disease. Quilostigmine is well absorbed from the gastrointestinal tract, but the oral bioavailability poor to moderate in rats and dogs because of pre-systemic metabolism. In preclinical studies has demonstrated activity in animal models of memory function. In clinical trials, Quilostigmine was well tolerated in healthy subjects up to a single dose of 64 mg and multiple doses of 60 mg QD for seven days

Diclofensine is an antidepressant with equipotent inhibitive effects on the neuronal uptake of norepinephrine (NE), serotonin, and dopamine. It is devoid of monoamine-releasing or monoaminoxidase-inhibiting properties. Diclofensine was found to be an effective antidepressant in human trials, with relatively few side effects, but was ultimately dropped from clinical development.