Furfenorex (unde brand name Frugalan), was used against obesity as an appetite suppressant. One of its metabolite was metamphetamine, which lead to the abuse to the drug. That is why this drug is no longer marketed

Indole-3-carbinol (I3C), a common phytochemical in cruciferous vegetables, and its condensation product, 3,3'-diindolylmethane (DIM) exert several biological activities on cellular and molecular levels, which contribute to their well-recognized chemoprevention potential. ndole-3-carbinol is used for prevention of breast cancer, colon cancer, and other types of cancer. The National Institutes of Health (NIH) has reviewed indole-3-carbinol as a possible cancer preventive agent and is now sponsoring clinical research for breast cancer prevention. Indole-3-carbinol is also used for fibromyalgia, tumors inside the voice box (laryngeal papillomatosis) caused by a virus, tumors inside the respiratory tract (respiratory papillomatosis) caused by a virus, abnormal cell growth in the cervix (cervical dysplasia), and systemic lupus erythematosus (SLE). Indole-3-carbinol scavenges free radicals and induces various hepatic cytochrome P450 monooxygenases. Specifically, this agent induces the hepatic monooxygenase cytochrome P4501A1 (CYP1A1), resulting in increased 2-hydroxylation of estrogens and increased production of the chemoprotective estrogen 2-hydroxyestrone. Accumulating evidence indicates that the antitumor activity of indole-3- carbinol is attributable to its ability to interfere with multiple oncogenic signaling pathways governing cell cycle progression, survival, invasion, and other aggressive phenotypes of cancer cells. Reported signaling targets of indole-3- carbinol in various cancer cell lines include EGFR/Src, Akt/NF-B, stress responses, elastase, and Rho kinase. Moreover, indole-3-carbinol functions as a negative regulator of estrogen action in hormonesensitive cancer cells through the inhibition of estrogen receptor (ER)-alpha signaling and/or induction of cytochrome P-450-mediated estrogen metabolism, suggesting its clinical use in hormone-sensitive cancers.

Oxfenicine is a CPT-1b-specific inhibitor. It must be transaminated to its active form, 4-hydroxyphenyl-glyoxylate, which is competitive with carnitine, preventing the formation of acylcarnitine. Because CPT-1b shows the highest sensitivity to 4-hydroxyphenyl-glyoxylate, inhibition of fatty acid oxidation by oxfenicine takes place selectively in those tissues that express this CPT isoform. It may be effective for treating noninsulin-dependent diabetes mellitus which is characterized by elevated fatty acid levels and obesity. In 1980 it was also tested in preclinical models of angina pectoris and ischemia.

Idalopirdine (Lu AE58054) is a Serotonin 6 receptor (5-HT6) antagonist. Idalopirdine exrets good oral bioavailability and robust efficacy in a rat model of cognitive impairment in schizophrenia. In rats idalopirdine potentiates the effects of acetylcholinesterase inhibitor donepezil on two pharmacodynamic biomarkers associated with cognition, i.e. neuronal oscillations and extracellular ACh levels in the hippocampus. Such potentiation could contribute to the procognitive effects of idalopirdine observed in donepezil-treated Alzheimer's disease patients. The compound is being developed by Lundbeck as an adjunctive therapy with acetylcholinesterase inhibitor donepezil, and is in phase III development for the treatment of Alzheimer's disease in multiple countries worldwide. A phase II trial for the treatment of cognitive impairment associated with schizophrenia was conducted; however no recent reports of development for idalopirdine have been identified.

Etiocholanedione is a natural metabolite of dehydroepiandrosterone with potent antiobesity activity. Etiocholanedione has been identified as a metabolite of an altered androgen metabolism that eventually leads hepatocellular carcinoma to impaired hormone responsiveness in human. Etiocholanedione has been identified as a metabolite of 17alpha-hydroxyprogesterone in some patients affected by congenital adrenal hyperplasia, although it doesn't appear to account for the masculinization observed in congenital hyperplasia.

MK-5046 is an orally active, potent, selective agonist of the orphan G protein-coupled receptor bombesin receptor subtype-3 (BRS-3). In pharmacological testing using diet-induced obese mice, MK-5046 caused mechanism-based, dose-dependent reductions in food intake and body weight.

Sazetidine-A (6-[5-(azetidin-2-ylmethoxy)pyridin-3-yl]hex-5-yn-1-ol or AMOP-H-OH) is a "silent desensitizer" of neuronal nicotinic acetylcholine receptors (nAChRs), meaning that it desensitizes the receptor without first activating it. Later it was shown that Sazetidine-A is an agonist of native and recombinant alpha4beta2 nAChRs but shows differential efficacy on alpha4beta2 nAChRs subtypes. In animal models it is able to regulate the gain in body weight, alcohol and nicotine dependence. Sazetidine-A exerts analgesic, antidepressant and anxiolytic properties.

PF-514273 is a drug developed by Pfizer, which acts as an extremely selective antagonist for the CB1 receptor, with approximately 10,000x selectivity over the closely related CB2 receptor. Pfizer was developing PF 514273 in phase I clinical studies for the treatment of obesity in the US. However, these studies were discontinued.

BMS-193885 is a potent and selective neuropeptide Y(1) receptor antagonist. BMS-193885 has 3.3 nM affinity at the neuropeptide Y(1) receptor, acting competitively at the neuropeptide Y binding site. BMS-193885 increased the K(d) of [(125)I]PeptideYY from 0.35 nM to 0.65 nM without changing the B(max) (0.16 pmol/mg of protein) in SK-N-MC cells that endogenously express the neuropeptide Y(1) receptor. It is also found to be a full antagonist with an apparent K(b) of 4.5 nM measured by reversal of forskolin (FK)-stimulated inhibition of cAMP production by neuropeptide Y. Pharmacological profiling showed that BMS-193885 has no appreciable affinity at the other neuropeptide Y receptors, and is also 200-fold less potent at the alpha(2) adrenergic receptor. BMS-193885 reduces food intake and body weight via inhibition of the central neuropeptide Y(1) receptor. BMS-193885 has good systemic bioavailability and brain penetration, but lacks oral bioavailability. BMS-193885, a potent and selective neuropeptide Y(1) receptor antagonist might be an efficacious treatment for obesity in humans.

GW-803430 is centrally active and selective antagonist of melanin-concentrating hormone receptor (MCHR) 1. GlaxoSmithKline was developing orally active, potent and selective GW-803430 for the treatment of obesity. GW803430 produces robust antiobesity and antidepressant-like effects in rodents.