Imiloxan is a highly selective alpha2B adrenoceptor antagonist and was developed for depression in the 1980s. In Phase 1 clinical trials imiloxan dosing led to hypersensitivity reactions; the molecule's development was discontinued.

Hydroxytamoxifen (Afimoxifene) is an active metabolite of tamoxifen exerting estrogen receptor modulatory function. In addition, hydroxytamoxifen binds to regulates transcriptional activity of the estrogen-related receptor gamma. ASCEND Therapeutics, Inc. was developing TamoGel (4-hydroxytamoxifen gel) for a variety of estrogen-dependent conditions, including breast cancer, cyclic breast pain and gynecomastia.

Thiorphan is the first potent synthetic inhibitor of enkephalinase. Thiorphan displays antinociceptive activity after systemic administration. Thiorphan also inhibits to a lesser extent the widely distributed angiotensin-converting enzyme, a carboxydipeptidase implicated in blood pressure regulation. Thiorphan failed to potentiate allergen-induced airway responses in asthma. Thiorphan significantly reduced the castor oil-induced diarrhea in rats when administered intravenously but not when administered intracerebroventricularly. Racecadotril, via its active metabolite thiorphan, was consistently effective in animal models and patients with various forms of acute diarrhea by inhibiting pathologic (but not basal) secretion from the gut without changing gastro-intestinal transit time or motility.

Swainsonine is an indolizidine alkaloid found in Australian Swainsona canescens, North American plants of the genera Astragalus and Oxytropis and also in the fungus Rhizoctonia leguminocola. It is competitive inhibitor of Golgi alpha-mannosidase II and lysosomal alpha-mannosidases. This compound has been reported to be a potent antiproliferative and immunomodulatory agent. However, no evidence of anti-tumor activity of swainsonine was seen in phase II clinical trial, in patients with locally advanced or metastatic renal cell carcinoma. Adverse events such as fatigue, nausea and diarrhea were common but generally mild. Swainsonine is locoweed toxin. Locoweed poisoning is seen throughout the world and annually costs the livestock industry millions of dollars. Swainsonine inhibits lysosomal alpha-mannosidase and Golgi mannosidase II. Poisoned animals are lethargic, anorexic, emaciated, and have neurologic signs that range from subtle apprehension to seizures.

Enzastaurin is a serine/threonine kinase inhibitor that showed antiangiogenic, antiproliferative, and proapoptotic properties in vitro and antitumor activity in vivo in a xenograft Waldenström macroglobulinemia (WM) model. Enzastaurin (LY317615) is a potent PKCβ selective inhibitor. Enzastaurin suppresses angiogenesis and was advanced for clinical development based upon this antiangiogenic activity. Enzastaurin suppresses tumor growth through multiple mechanisms: direct suppression of tumor cell proliferation and the induction of tumor cell death coupled to the indirect effect of suppressing tumor-induced angiogenesis. Enzastaurin is an orally administered drug that was intended for the treatment of solid and haematological cancers. Enzastaurin had shown encouraging preclinical results for the prevention of angiogenesis, inhibition of proliferation and induction of apoptosis as well as showing limited cytotoxicity within phase I clinical trials. However, during its assessment in phase II and III clinical trials the efficacy of enzastaurin was poor both in combination with other drugs and as a single agent. Eli Lilly discontinued development of enzastaurin after top-line data from the double-blind, international Phase III PRELUDE trial in 758 DLBCL patients showed that enzastaurin missed the primary endpoint of improving DFS vs. placebo.

Etazolate (EHT-0202) is a selective, positive GABAA receptor modulator has completed phase II clinical trials in patients with Alzheimer's disease. It is also a selective phosphodiesterase-4 inhibitor that is specific for cAMP. Etazolate showed anxiolytic and antidepressant activity and could be useful in managing post-traumatic stress disorder.

Lysergide (LSD) is a semi-synthetic hallucinogen and is one of the most potent drugs known. Recreational use became popular between the 1960s to 1980s, but is now less common. LSD was first synthesized by Albert Hoffman while working for Sandoz Laboratories in Basel in 1938. Some years later, during a re-evaluation of the compound, he accidentally ingested a small amount and described the first ‘trip’. During the 1950s and 1960s, Sandoz evaluated the drug for therapeutic purposes and marketed it under the name Delysid®. It was used for research into the chemical origins of mental illness. Recreational use started in the 1960s and is associated with the ‘psychedelic period’. LSD possesses a complex pharmacological profile that includes direct activation of serotonin, dopamine and norepinephrine receptors. In addition, one of its chief sites of action is that of compound-specific (“allosteric”) alterations in secondary messengers associated with 5HT2A and 5HT2C receptor activation and changes in gene expression. The hallucinogenic effects of LSD are likely due to agonism at 5HT2A and 5HT2C receptors. LSD is also an agonist at the majority of known serotonin receptors, including 5HT1A, 5HT1B, 5HT1D, 5HT5A, 5HT6 and 5HT7 receptors. During the 1960s, LSD was investigated for a variety of psychiatric indications, including the following: as an aid in treatment of schizophrenia; as a means of creating a "model psychosis"; as a direct antidepressant; and as an adjunct to psychotherapy. LSD is listed in Schedule I of the United Nations 1971 Convention on Psychotropic Substances.

Lysergide (LSD) is a semi-synthetic hallucinogen and is one of the most potent drugs known. Recreational use became popular between the 1960s to 1980s, but is now less common. LSD was first synthesized by Albert Hoffman while working for Sandoz Laboratories in Basel in 1938. Some years later, during a re-evaluation of the compound, he accidentally ingested a small amount and described the first ‘trip’. During the 1950s and 1960s, Sandoz evaluated the drug for therapeutic purposes and marketed it under the name Delysid®. It was used for research into the chemical origins of mental illness. Recreational use started in the 1960s and is associated with the ‘psychedelic period’. LSD possesses a complex pharmacological profile that includes direct activation of serotonin, dopamine and norepinephrine receptors. In addition, one of its chief sites of action is that of compound-specific (“allosteric”) alterations in secondary messengers associated with 5HT2A and 5HT2C receptor activation and changes in gene expression. The hallucinogenic effects of LSD are likely due to agonism at 5HT2A and 5HT2C receptors. LSD is also an agonist at the majority of known serotonin receptors, including 5HT1A, 5HT1B, 5HT1D, 5HT5A, 5HT6 and 5HT7 receptors. During the 1960s, LSD was investigated for a variety of psychiatric indications, including the following: as an aid in treatment of schizophrenia; as a means of creating a "model psychosis"; as a direct antidepressant; and as an adjunct to psychotherapy. LSD is listed in Schedule I of the United Nations 1971 Convention on Psychotropic Substances.

PHA-543613 was discovered by Pfizer and has been under development primarily as a potential treatment of schizophrenia. PHA-543613 acts as an agonist to the Neuronal acetylcholine receptor protein alpha-7 subunit. A single human trial was conducted in healthy human volunteers, but the compound has been studied extensively in rat models for schizophrenia as well as Parkinson's disease and Alzheimer's disease.

PHA-543613 was discovered by Pfizer and has been under development primarily as a potential treatment of schizophrenia. PHA-543613 acts as an agonist to the Neuronal acetylcholine receptor protein alpha-7 subunit. A single human trial was conducted in healthy human volunteers, but the compound has been studied extensively in rat models for schizophrenia as well as Parkinson's disease and Alzheimer's disease.