Perzinfotel (EAA-090) is a novel squaric acid amide derivative that has been identified as a potential treatment for ischemic brain damage resulting from stroke. EAA-090 is a competitive inhibitor at the NMDA-selective subtype of the glutamate receptor. The compound demonstrates potent inhibitory activity in both in vitro and in vivo models of NMDA-induced excitotoxicity and provides neuroprotective efficacy in several animal models of stroke. EAA-090 is unique among competitive NMDA antagonists in displaying a clear separation between predicted efficacious dose and doses that induce PCP-like psychotomimetic side effects in both animals and humans. This unique profile makes EAA-090 an exciting candidate for assessing the neuroprotective potential of the competitive NMDA mechanism.

Denbufylline is a selective xanthine derivative that inhibits PDE IV and has bronchodilatory properties. Shown to exhibit negative inotropic effects by acting on verapamil-sensitive sites of Ca2+ channels in guinea pig ventricle papillary muscle independently of its PDE inhibitory activity. Denbufylline, a selective type 4 phosphodiesterase (PDE-4) inhibitor, is a potent activator of the hypothalamo-pituitary-adrenal (HPA) axis when given orally or intraperitoneally (i.p.) to adult male rats. Denbufylline was being developed as an agent for the therapy of dementia.

Clorotepine (aka octoclothepin or octoclothepine) is an antipsychotic from the tricyclic group derived from perathiepin. It was originally developed in 1965 and marketed in the Czech Republic by Spofa in or around 1971 for the treatment of schizophrenic psychosis. Clorotepine has a high affinity for the dopamine (D1, D2, D3, D4), receptors the serotonin 5-HT (2A, 2B, 2C, 6, 7) receptors, the alpha-adrenergic receptors (1A, 1B, 1D), and the histamine H1 receptors. In most instances, it acts as an antagonist (or inverse agonist). Clorotepine will also block the reuptake of norepinephrine by inhibiting the norepinephrine transporter.

Omigapil (CGP 3466 or TCH346) is a structurally related analog of R-(-)-deprenyl that exhibits virtually no monoamine oxidase type B inhibiting activity but is neuroprotective in the picomolar concentration range. It binds to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and at subnanomolar concentrations prevent the S-nitrosylation of GAPDH, inhibit GAPDH-Siah binding and prevent the nuclear translocation of GAPDH. Omigapil demonstrated promising potential in the treatment of Parkinson's disease and motoneuron disease in animal models, however, it did not show efficacy in clinical trials. Omigapil is in development for the treatment of congenital muscular dystrophy.

Enilospirone (CERM-3726) is essentially a central stimulant. At low doses (100 mg) it may improve performance and at higher doses it may lead to disturbance of sleep continuity. These effects may not involve DA mechanisms, though changes such as those in REM sleep with chronic ingestion could involve the noradrenergic pathway. The property of the drug, even at low doses, to oppose the deterioration in performance associated with tests of prolonged duration is likely to be due to a mild alerting effect.

Pardoprunox is a partial D2/3 dopamine receptor agonist and full 5-HT1A serotonin receptor agonist. Partial D(2/3) dopamine (DA) receptor agonists provide a novel approach to the treatment of the motor symptoms of Parkinson's disease that may avoid common dopaminergic side effects, including dyskinesia and psychosis. Pardoprunox passed phase III clinical trial for the treatment of Parkinson's disease.

FLUBANILATE is a CNS stimulant.

Eticlopride {2S(−)-3-chloro-5-ethyl-N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-hydroxy-2-methoxybenzamide} is an antagonist at dopamine D2 and D3 receptors. It is widely used for in vivo, in vitro, and ex vivo examination of D2/D3 receptors densities and function. Eticlopride exerts antipsychotic activity in animals.

Pruvanserin (EMD 281014, LY-2422347) is a selective serotonin 5-HT2A receptor antagonist. Pruvanserin was originated by Merck KGaA. Eli Lilly had been developing pruvanserin, under a global licence from Merck KGaA, for the treatment of primary insomnia and major depressive disorder. Phase II trials were completed in the US, Hungary and Spain. However, development appears to have been discontinued.

MK-0686 is a bradykinin B1 receptor antagonist patented by American multinational pharmaceutical company Merck & Co for the treatment of neuropathic pain and inflammation. MK-0686 demonstrates significantly reduced susceptibility to human P-gp mediated efflux and shows good potential for human CNS penetration based on brain levels in CF-1 mice and monkeys. Additionally, MK-0686 also exhibited good CNS bradykinin B1 receptor occupancy in the transgenic rat expressing the human B1 receptor and showed oral efficacy in reducing CFA-induced hyperalgesia in a humanized mouse. Unfortunately, in phase II clinical trials MK-0686 failed to demonstrate efficacy in phase II clinical trials.