Serazapine (CGS15040) is an anxiolytic agent. It is structurally novel 5-HT2 receptor antagonist. Preliminary preclinical findings indicated an anticonflict effect in a behavioral suppression test, and two preliminary investigations in volunteers also suggested anxiolytic potential. In the first of these studies serazapine resembled diazepam, a reference anxiolytic drug, electroencephalographically. Additionally, in a test of psychogenic stress in volunteers it reduced cardiac output.

Triflubazam is a 1,5-benzodiazepine derivative. The hypnotic activity of the 1,5-benzodiazepines is limited, and that this is particularly so in the case of triflubazam. Subjects reported impaired sleep with triflubazam (40 mg), and a sense of less wakefulness the morning. The effect of triflubazam may have persisted beyond the night of ingestion. No effect of triflubazam was observed on total sleep time, stage shifts in the first 6 h or latency to the first rapid eye movement period of sleep. Triflubazam has psychopharmacological properties in animals suggestive of antianxiety activity of a longer duration than that of diazepam. The metabolism of triflubazam by man is characterized by extensive N-demethylation, aromatic hydroxylation, aromatic O-methylation and dihydrodiol formation.

Suriclone is a dithiinopyrrole derivative patented by Rhone-Poulenc S. A. as a sedative and anxiolytic drug. The mechanism of action by which suriclone produces it's sedative and anxiolytic effects is by modulating GABAA receptors, although suriclone is more subtype-selective than most benzodiazepines. In clinical trials, Suriclone shows a significant anxiolytic effect. The most common adverse reaction was dizziness.

Metaclazepam is a benzodiazepine derivative. It exerts anxiolytic properties.

Lorglumide (CR1409) is the first nonpeptidic, selective and potent inhibitor of the cholecystokinin-A and cholecystokinin-B receptors. Lorglumide prevented dose-dependently the emptying of the gallbladder in both experimental models; proglumide exhibited a comparable activity at much higher doses. Lorglumide was associated with significantly inhibited cell growth of human pancreatic cancer cell line Mia PaCa-2 in vitro. Lorglumide also induced G0/G1 cell cycle arrest and apoptosis. The change of invasion ability appeared to be mediated by MMP-2 expression, which was upregulated by CCK-8S and downregulated by lorglumide. Lorglumide had been in preclinical phase for the treatment of biliary dyskinesia, pancreatitis and cancer. However, this development was discontinued.

Proflazepam is benzodiazepine derivative patented by Hoffmann-La Roche, F., und Co., A.-G. as anticonvulsant and muscle relaxant. In preclinical studies, Proflazepam shows activity in pentetrazole test and in the rotating rod test.

Cloroperone (AHR 6134) is a derivative of butyrophenone with anxiolytic properties. In animals, cloroperone causes slight CNS depression in mice, prevents the lethal effects of d-amphetamine under crowded conditions in mice, suppresses emesis in dogs. The drug was investigated in the clinic for the treatment of psychotic patients. It was shown to be effective anxiolytic at low dosages without sedation, listlessness, drowsiness or neurologic reactions. Cloroperone is a selective binder to 5-HT2 receptors (Ki 4.5 nM).

Meclonazepam (Ro11-3128 or 3-methylclonazepam) is a benzodiazepine derivative. It exerts anxiolytic activity. Meclonazepam demonstrated anti-schistosomal action, it causes spastic paralysis, calcium influx and tegumental disruption in the parasites. Contracturant effect of meclonazepam is not a result of its binding to the worm benzodiazepine binding sites.

Orvepitant is a novel generation brain penetrant, selective and potent, small molecule NK-1 receptor antagonist. Orvepitant’s (GW823296) mode of action and developability characteristics made it a suitable development candidate for the treatment of common anxiety disorders, posttraumatic stress disorder and major depressive disorder. It’s in phase II clinical trials as an effective inhibitor of itch-associated response.

Pagoclone is an anxiolytic agent from the cyclopyrrolone family, related to better-known drugs such as the sleeping medication zopiclone. It binds with the roughly equivalent high affinity (0.7–9.1 nM) to the benzodiazepine binding site of human GABAA receptors containing either a α1, α2, α3 or α5 subunit. It is a partial agonist at α1-, α2- and α5-containing GABAA receptors and a full agonist at receptors containing a α3 subunit. Pagoclone produces anxiolytic effects with little sedative or amnestic actions at low doses.