Pregnanediol is a chief steroid metabolite of progesterone that is biologically inactive and occurs as pregnanediol glucuronate in the urine. Pregnanediol has two hydroxyl groups, at 3-alpha and 20-alpha. A test can be done to measure the amount of pregnanediol in urine. The urine test offers an indirect way to measure progesterone levels in the body. It is a standard in the colorimetric determination of urinary pregnanediol in clinical laboratories.

Amicus Therapeutics was investigating afegostat (isofagomine; Plicera; HGT-3410; AT-2101), an orally available pharmacological chaperone molecule, which binds to glucocerebrosidase (Gba) and stimulates proper folding and trafficking of the enzyme, for the potential treatment of Parkinsons disease(PD) and Gaucher disease. Afegostat specifically and reversibly binds GCase in the ER with highaffinity; this stabilizes the active form of the enzyme in the ER and increases trafficking of GCase to lysosomes. In 2006, Orphan Drug designations were granted in the U.S. and E.U. in 2006 and 2007, respectively. However, this research has been discontinued.

Levomequitazine is the L-enantiomer of mequitazine. The antihistaminergic activity mainly resides in the S-enantiomer, L-mequitazine, whereas the anticholinergic activity mainly resides in the D-enantiomer. It was shown, that L-enantiomer of mequitazine is less potent antagonist of human M3 muscarinic acetylcholine receptors than D-enantiomer. In vitro binding studies have shown that the affinity of L-mequitazine for H1 receptors is approximately ten times higher and to muscarinic receptors ten times lower, compared to d-mequitazine. Memory impairment was observed after administration of L-mequitazine 10 mg alone on delayed recall. This could be due to indirect effects of H1 receptor blockade. L-mequitazine 10 mg produced mild driving impairment, whereas L-mequitazine 2.5 and 5.0 mg show no effects on driving. Levomequitazine had been in phase III clinical trials by Pierre Fabre for the treatment of perennial allergic rhinitis and seasonal allergic rhinitis.

Nicotredole (Tryptamide), similarly to ibuprofen and piroxicam, shows anti-inflammatory and analgesic properties. Tryptamide reversed pyrogen-induced hyperthermia in rats, elicited analgesic effects in rats, but not in mice, prolonged the time of hexobarbital sleep in rats and inhibited locomotor activity in rats and mice. Tryptamide has not elicited side effects on the circulatory system of rats and cats.

Bardoxolone methyl, the C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) known as CDDO-Me or RTA 402, is one of the derivatives of synthetic triterpenoids. Bardoxolone methyl directly blocks IKKbeta activity and thereby the NF-kappaB pathway by interacting with Cys-179 in the IKKbeta activation loop. Binding of bardoxolone methyl to Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1) disrupts its critical cysteine residues, leading to the release of the nuclear factor erythroid 2-related factor 2 (Nrf2), which hinders its ubiquitination and finally leads to its stabilization and nuclear translocation. In the nucleus, Nrf2 activates the transcription of phase 2 response genes, leading to a coordinated antioxidant and anti-inflammatory response. In addition, it acts as an antagonist of the peroxisome proliferator-activated receptor gamma. Through Keap1/Nrf2 and nuclear factor-κB pathways, this agent can modulate the activities of a number of important proteins that regulate inflammation, redox balance, cell proliferation and programmed cell death. This agent is generally well tolerated, but it may increase adverse cardiovascular events. Presently, it is being further tested for the treatment of patients with chronic kidney disease, cancer, and pulmonary arterial hypertension.

Belaperidone (LU111995) is a recently identified antipsychotic agent with high 5-hydroxytryptamine2 and dopamine D4 receptor affinities as well as D4 versus D2 receptor selectivity. The drug did not produce catalepsy. LU111995 prolongs the Q-T interval to a limited degree and is not arrhythmogenic over the physiological range of cycle lengths. Belaperidone had been in phase II clinical trials for the treatment of schizophrenia. However, the study about this drug candidate was discontinued.

Fenmetozole is an alpha-2 adrenergic receptor antagonist which was developed for the treatment of schizophrenic and/or depressed patients, however never reached the market. It was also shown that the drug may reduce symptoms of minimal brain dysfunction in children and antagonize the effect of barbiturates and ethanol.

Ciladopa, is a troponylpiperazine derivative and dopamine agonist that has been shown to influence dopaminergic mechanisms in animals. Preclinical pharmacological studies have suggested that it has antiparkinsonian activity similar to that of bromocriptine but without many of the troublesome side effects. Unfortunately in some clinical trials no significant differences was found among the treatment groups and placebo.

Eticyclidine (N-ethyl-1-phenylcyclohexylamine) is a phencyclidine derivative exerting nearly the same pharmacological profile as the parent compound. In rodents, it induces stereotypy, ataxia, interoceptive effect and hypothermia.

Enadoline (CI-977) is a potent and selective agonist at the kappa-opioid receptor. Enadoline is a potent antinociceptive agent. Clinical use of enadoline was associated with dose-limiting neuropsychiatric adverse events. Enadoline may yet find some application against ischaemic stroke and severe head injury, presumably in comatose patients.