(R)-SKF-83959 (MCL 202) is enantiomer of D1 receptor agonist SKF-83959. (R)-SKF-83959 is reported to be a functionally selective dopamine D1 and D5 receptors ligand with much lower affinity to dopamine D2 and D3 receptors. (R)-SKF-83959 like SKF-83959, produced dose related effects on overt behavior (eye blinking) and schedule-controlled performance in squirrel monkeys. (R)-SKF-83959 increases in eye blinking and decreases in rates of fixed-ratio responding. In contrast to the effects of its S-(-) enantiomer, was relatively devoid of behavioral activity up to doses that were approximately 10-fold greater than (R)-SKF-83959. Pretreatment with the selective D1- like receptor antagonist SCH 39166 dose-dependently antagonized increases in eye blinking produced by (R)-SKF-83959, confirming the involvement of D1 mechanisms in its effects.

J-113397 (ComB) is the first potent and selective small molecule ORL1 antagonist. Merck, in collaboration with Banyu, is developing J-113397 with potential use in the treatment of pain. Preclinical development is underway in Japan, however, no recent development has been reported. In addition to antinociceptive properties J-113397 exerts antiparkinsonian action in animal models.

Celastrol is a pentacyclic triterpenoid isolated from the root extracts of Tripterygium wilfordii, a perrennial creeping plant indigenous to large area in Southern China. Celastrol possess antioxidant and anti-inflammatory and anticancer action. In the mouse model of rheumatoid arthritis it reduced inflammatory swelling, suppressed humoral and skin response and reduced pathological progression of joint. Celastrol demonstrated efficacy in transgenic mouse model of amyotrophic lateral sclerosis. Anticancer activity of celastrol was shown in xenograft models of prostate cancer. Celastrol suppresses food intake, blocks reduction of energy expenditure, and leads to up to 45% weight loss in hyperleptinemic diet-induced obese (DIO) mice by increasing leptin sensitivity. Celastrol acts by interfering with the activity of Hsp90, IKK-beta and proteasome S26 subunit.

PNU-282987 is a potent and selective a7 nAChR agonist. This compound showed high affinity for the rat a7 nAChR (Ki = 26 nM) and activity at the a7–5-HT3 chimera (EC50 = 128 nM). In addition, PNU-282987 was found to be inactive at all tested monoamine, muscarine, glutamate, and GABA receptors at 1 uM concentration, except 5-HT3 receptors (Ki = 930 nM). The highly selective and potent a7 nAChR agonist PNU-282987 enhances GABAergic synaptic activity in the hippocampus in vitro, and reverses amphetamine induced auditory gating deficit in anesthetized rats. In addition, PNU-282987 improves the inherent gating deficit observed in a subset of rats and enhances amphetamine induced hippocampal activity. These results support the concept that a7 nAChR agonists represent a novel, potential pharmacotherapy in treatment of schizophrenia. It also has being shown that acute lung injury is reduced by PNU-282987 through changes in the macrophage profile.

AK-7 is a brain penetrant selective SIRT2 inhibitor. AK-7 exerts neuroprotective properties in vitro and in vivo models of neurodegenerative diseases (Huntington’s, Parkinson’s and Alzheimer’s disease).

JNJ-1661010 is a potent and selective is a potent and selective fatty acid amide hydrolase (FAAH) inhibitor. FAAH is a membrane bound serine hydrolase primarily responsible for the breakdown of the endogenous cannabinoid anandamide in the CNS. Increasing the amount of anandamide, which has analgesics properties, may be efficacious in the treatment of pain. According to the experimental data JNJ-1661010 may be useful clinically as broad-spectrum analgesics. Johnson & Johnson is developing JNJ-1661010 for the treatment of neuropathic pain. Preclinical development is being conducted in the US. In addition recent data demonstrated that JNJ-1661010 could be useful in the treatment of arthritis and parkinson's disease. JNJ-1661010 inhibits myometrial contractility, without un-specific relaxing effects on the smooth muscle.

Echinacoside is a caffeic acid glycoside which is constituted from a trisaccharide consisting of two glucose and one rhamnose moieties glycosidically linked to one caffeic acid and on hydroxytyrosol residue at the centrally situated rhamnose. Echinacoside is the basic component of the roots of E. angustifolia and E. pallida, ranging from 0.5 to 1.0%. Echinacoside is reported to possess the immunostimulatory and high antioxidant activities

N-Ethyl-3-piperidyl benzilate (JB-318) is an anticholinergic drug. It is a potent hallucinogenic agent. JB-318 is a psychotomimetic, it has an antitremor action in patients with Parkinson disease.

SCH-58261 is an antagonist of the Adenosine A2A receptor with a Kd of 2.3 nM. It was initially identified and developed by Schering-Plough as a potential treatment for neurological conditions such as Parkinson's Disease and Depression. However, the compound suffered from poor solubility and is not active when orally dosed. SCH-58261 became the scaffold for the development of Preladenant (SCH 412348), which did progress to Phase III clinical trials before being discontinued. There has also been an investigation of SCH-58261 as a treatment of hypotension in rat models.

LY404187 (or LY-404,187) is a selective, potent and centrally active positive allosteric modulator of AMPA receptors. LY404187 preferentially acts at recombinant human homomeric GluR2 and GluR4 versus GluR1 and GluR3 AMPA receptors. This drug, developed by Eli Lilly and Company, is a member of biarylpropylsulfonamides. LY404187 has been shown to enhance performance in animal models of cognitive function requiring different mnemonic processes and may be therapeutically beneficial for treating cognitive deficits in a variety of disorders, particularly those that are associated with reduced glutamatergic signaling such as schizophrenia. In addition, LY404187 has been demonstrated to be efficacious in animal models of behavioral despair that possess considerable predictive validity for antidepressant activity and Parkinson's disease.