Lipoic acid (LA), also known as α-lipoic acid and alpha lipoic acid (ALA) and thioctic acid, is an organosulfur compound derived from caprylic acid. ALA is made in animals normally, and is essential for aerobic metabolism. It is also manufactured and is available as a dietary supplement in some countries where it is marketed as an antioxidant, and is available as a pharmaceutical drug in other countries.
Cytochrome P450 3A4 is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from the body.
Iprindole, sold under the brand names Prondol, Galatur, and Tertran, is an atypical tricyclic antidepressant (TCA) that has been used in the United Kingdom and Ireland for the treatment of depression but appears to no longer be marketed. It was developed by Wyeth and was marketed in 1967. The drug has been described by some as the first "second-generation" antidepressant to be introduced. However, it was very little-used compared to other TCAs, with the number of prescriptions dispensed only in the thousands.
Flunoxaprofen, also known as Priaxim, is a chiral nonsteroidal anti-inflammatory drug (NSAID). It is closely related to naproxen, which is also an NSAID. Flunoxaprofen has been shown to significantly improve the symptoms of osteoarthritis and rheumatoid arthritis. The clinical use of flunoxaprofen has ceased due to concerns of potential hepatotoxicity.
Benoxaprofen, also known as Benoxaphen, is a chemical compound with the formula C16H12ClNO3. It is a nonsteroidal anti-inflammatory drug (NSAID) and was marketed under the brand name Oraflex in the United States and as Opren in Europe by Eli Lilly and Company. Lilly suspended sales of Oraflex in 1982 after reports from the British government and the U.S. Food and Drug Administration (FDA) of adverse effects and deaths linked to the drug.
Picenadol (LY-97435) is a 4-phenylpiperidine derivative that is an opioid analgesic drug developed by Eli Lilly in the 1970s.
Solute carrier family 22 member 8, or organic anion transporter 3 (OAT3), is a protein that in humans is encoded by the SLC22A8 gene.
Zacopride is a potent antagonist at the 5-HT3 receptor and an agonist at the 5-HT4 receptor. It has anxiolytic and nootropic effects in animal models, with the (R)-(+)-enantiomer being the more active form. It also has antiemetic and pro-respiratory effects, both reducing sleep apnea and reversing opioid-induced respiratory depression in animal studies. Early animal trials have also revealed that administration of zacopride can reduce preference for and consumption of ethanol.
TPA-023 (MK-0777) is an anxiolytic drug with a novel chemical structure, which is used in scientific research. It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic. It is a subtype-selective, mixed agonist-antagonist at GABAA receptors, which acts as a partial agonist at the α2 and α3 subtypes, but as a silent antagonist at α1 and α5 subtypes. It has primarily anxiolytic and anticonvulsant effects in animal tests, but with no sedative effects even at 50 times the effective anxiolytic dose.
Oxaprotiline, also known as hydroxymaprotiline, is a norepinephrine reuptake inhibitor of the tetracyclic antidepressant (TeCA) family that is related to maprotiline. Though investigated as an antidepressant, it was never marketed.
Tametraline (CP-24,441) is the parent of a series of chemical compounds investigated at Pfizer that eventually led to the development of sertraline (CP-51,974-1).
6-Br-APB is a synthetic compound that acts as a selective D1 agonist, with the (R)-enantiomer being a potent full agonist, while the (S) enantiomer retains its D1 selectivity but is a weak partial agonist. (R)-6-Br-APB and similar D1-selective full agonists like SKF-81,297 and SKF-82,958 produce characteristic anorectic effects, stereotyped behaviour and self-administration in animals, with a similar but not identical profile to that of dopaminergic stimulants such as amphetamine.
The eudysmic ratio represents the difference in pharmacologic activity between the two enantiomers of a drug. In most cases where a chiral compound is biologically active, one enantiomer is more active than the other. The eudysmic ratio is the ratio of activity between the two. A eudysmic ratio significantly differing from 1 means that they are statistically different in activity.
d-Deprenyl, also known as or dextro-N-propargyl-N-methylamphetamine, is an MAO-B inhibitor that metabolizes into d-amphetamine and d-methamphetamine and is therefore also a norepinephrine-dopamine releasing agent. It is the opposite enantiomer of l-deprenyl (selegiline).
Almoxatone (MD-780,236) is a selective and reversible inhibitor of MAO-B. It was patented as an antidepressant and antiparkinsonian agent but was never marketed.
(+)-Naloxone (dextro-naloxone) is a drug which is the "unnatural" enantiomer of the opioid antagonist drug (−)-naloxone. Unlike "normal" naloxone, (+)-naloxone has no significant affinity for opioid receptors, but instead has been discovered to act as a selective antagonist of Toll-like receptor 4. This receptor is involved in immune system responses, and activation of TLR4 induces glial activation and release of inflammatory mediators such as TNF-α and Interleukin-1.
Clorotepine, also known as octoclothepin or octoclothepine, is an antipsychotic of the tricyclic group which was derived from perathiepin in 1965 and marketed in the Czech Republic by Spofa in or around 1971 for the treatment of schizophrenic psychosis.
Ritalinic acid is a substituted phenethylamine and an inactive major metabolite of the psychostimulant drugs methylphenidate and ethylphenidate. When administered orally, methylphenidate is extensively metabolized in the liver by hydrolysis of the ester group yielding ritalinic acid. The hydrolysis was found to be catalyzed by carboxylesterase 1 (CES1).
Acetothiolutamide is a selective androgen receptor modulator (SARM) derived from the nonsteroidal antiandrogen bicalutamide that was described in 2002 and was one of the first SARMs to be discovered and developed. It is a high-affinity, selective ligand of the androgen receptor (AR), where it acts as a full agonist in vitro, and has in vitro potency comparable to that of testosterone. However, in vivo, acetothiolutamide displayed overall negligible androgenic effects, though significant anabolic effects were observed at high doses. In addition, notable antiandrogen effects were observed in castrated male rats treated with testosterone propionate. The discrepancy between the in vitro and in vivo actions of acetothiolutamide was determined to be related to rapid plasma clearance and extensive hepatic metabolism into a variety of metabolites with differing pharmacological activity, including AR partial agonism and antagonism. In accordance with its poor metabolic stability, acetothiolutamide is not orally bioavailable, and shows activity only via injected routes such as subcutaneous and intravenous.
Burapitant (SSR-240,600) is a drug developed by Sanofi-Aventis which was one of the first compounds developed that acts as a potent and selective antagonist for the NK1 receptor. While burapitant itself did not proceed beyond early clinical trials and was never developed for clinical use in humans, promising animal results from this and related compounds have led to a number of novel drugs from this class that have now been introduced into medical use.
