WAY 208466 dihydrochloride is a high affinity, selective SR-6 (5-HT6) receptor agonist. WAY-208466 produced both antidepressant-like and anxiolytic-like effects. Direct infusion of WAY-208466 into the dorsal raphe nucleus, locus coeruleus, basal forebrain (horizontal limb of the diagonal band of Broca) or laterodorsal tegmental nucleus specifically decreased REM sleep without significantly altering wakefulness or slow wave sleep.

LY-300168 (GYKI-53655) is a negative allosteric AMPA modulator. It is used as a tool compound to study role of AMPA receptor in CNS functioning. Administration of LY-300168 demonstrated anxyolitic effects. GYKI-53655 produced a dose-dependent prolongation of survival time in the MgCl2 induced global ischaemia model.

SL651498 was identified as a drug development candidate from a research program designed to discover subtype-selective GABA(A) receptor agonists for the treatment of generalized anxiety disorder and muscle spasms. SL651498 displayed high affinity for GABA(A) receptors containing alpha(1) and alpha(2 subunits, and weaker affinity for alpha5-containing GABA(A) receptors, it behaved as a full agonist at recombinant t GABA(A) receptors containing alpha(2) and alpha(3) subunits, and as a partial agonist at recombinant GABA(A) receptors expressing alpha(1) and alpha(5) subunits. It was shown, that SL651498 represented a promising alternative to agents currently used for the treatment of anxiety disorders and muscle spasms without the major side effects seen with classical benzodiazepines).

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.

JNJ-31020028 was shown to have high affinity for both human and rodent Y2 receptors. The antagonistic property of JNJ-31020028 for the Y2 receptor was demonstrated via inhibition of PYY-stimulated calcium response in KAN-Ts cells expressing a chimeric G protein. After subcutaneous administration, the Y2 antagonist was found to penetrate into the brain and dose dependently occupy Y2 receptor binding sites, demonstrating that the compound engaged its target in the CNS. JNJ-31020028 (15 mg/kg, s.c.) did reverse the anxiogenic effects of withdrawal from a single bolus dose of alcohol on the elevated plus-maze, confirming the anxiolytic-like properties of Neuropeptide Y2 antagonism. JNJ-31020028 has antidepressant like effects in the olfactory bulbectomized model.

ATC-0065 is an oral antagonist of melanin concentrating hormone receptor 1. In preclinical testing ATC-0065 demonstrated anxiolytic and antidepressant activity.

ATC-0175 is a potent antagonist with a high affinity for MCH1R and additional affinities for 5-HT1A and 5-HT2B receptors. The receptor binding and the functional assay (MCH-induced increase in [Ca2+]i) indicated that ATC0175 is a noncompetitive antagonist at MCH1Rs. ATC-0175 exhibited anxiolytic effects in numerous animal models of anxiety including the elevated plus-maze test, social interaction test, stress-induced hyperthermia and maternal separation-induced vocalization. ATC-0175 also exhibited antidepressant effects in the forced swimming test. ATC-0175 increased swimming performance without altering climbing behavior, as observed with selective serotonin reuptake inhibitors. ATC0175 has adequate ADME profile (reasonable oral bioavailability and brain penetration) and potent oral activity in animal models. In contrast, ATC-0175 did not affect spontaneous locomotor activity, hexobarbital-induced sleeping time and did not impair rotarod performance. Thus, ATC-0175 may be devoid of unwanted central nervous system side effects, which are sometimes observed with current medications. ATC-0175 has the potential to be effective in the treatment of patients with depression and/or anxiety disorders.

A-841720, a novel, potent and non-competitive mGluR1 antagonist in models of pain and of motor and cognitive function, is being under development by Merz Pharmaceuticals GmbH. It is a selective non-competitive mGlu1 receptor antagonist (IC50: 10 nM); showing 34-fold selectivity over mGluR5 and no significant activity at other mGluR receptors, neurotransmitter receptors, ion channels, and transporters. A-841720 demonstrated full efficacy in various in vivo animal pain models.

Rosavin is a glycoside found in the plant Rhodiola rosea. It is a component of rosavin capsules from Ameriden which are marketd to reduce stress and anxiety.

PD 176252 is a competitive antagonist of neuromedin-B preferring (BB1) and gastrin-releasing peptide preferring (BB2) receptors. PD176252 inhibited tumor growtn in preclinical model of lung cancer, and exhibited synergy with EGFR inhibitor in the model of head and neck cancer. PD176252 demonstrated anxiolytic properties in preclinical models.