SB-699551 is the first selective serotonin 5A receptor antagonist. SB-699551 showed an anxiolytic-like property in animal model. It demostrated efficacy against schizophrenia-like cognitive deficits and negative symptoms in rats. Blockade of 5-HT5A receptor with SB-699551 appear to be able to impair the consolidation of memory in rodents. In addition, 5-HT-induced spinal antinociception in the capsaicin and acetic acid tests was blocked by SB-699551.

PNU-177864 is a selective antagonist of D3 receptor. Compound was considered as a drug candidate for the chronic treatment of schizophrenia, but severe myopathy was found in skeletal muscles of rats during the initial safety evaluation of PNU-177864. Myopathy was associated with phospholipidosis in numerous tissues.

N-(4-(2-Methoxyphenoxy)-phenyl-N-(2,2,2-trifluoroethylsulfonyl)-pyrid-3-ylmethylamine (LY487379) is a selective positive allosteric modulator at metabotropic glutamate subtype 2 receptors (mGluR2). The compound exerts antipsychotic and anxiolytic actions.

Propylnorapomorphine is a potent and selective D2 receptor agonist. Propylnorapomorphine is used as a tool compound to label dopamine receptors in rodent brain, and elicits dopaminergic behavioural effects. It stimulates motor activity, induces stereotypic behaviour and sexual stimulation. Propylnorapomorphine was investigated in clinical trial against Parkinson's disease and schizophrenia

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.

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.

A-582941 was found to exhibit high-affinity binding and agonism at alpha-7 nicotinic acetylcholine receptor (α7-nAChR), with acceptable pharmacokinetic properties and excellent distribution to the central nervous system. In vitro and in vivo studies indicated that A-582941 activates signaling pathways known to be involved in cognitive function such as ERK1/2 and CREB phosphorylation. A-582941 enhanced cognitive performance in behavioral assays including the monkey delayed matching-to-sample, rat social recognition, and mouse inhibitory avoidance models that capture domains of working memory, short-term recognition memory, and long-term memory consolidation, respectively. AbbVie is developing α7-nAChR agonists including A-582941 as neuroprotective agents for the treatment of cognitive disorders such as Alzheimer's disease and schizophrenia. Development is at the preclinical stage.

Idazoxan is an alpha2 receptor antagonist which also shows activity at imidazoline I1 and I2 receptors and modulates the release of dopamine. Idazoxan was in phase II development in the US. Later the development of idazoxan for schizophrenia was discontinued. It was also in clinical trials for cognition disorders in United Kingdom, and was also discontinued. Idazoxan is used in scientific research as a tool for the study of alpha 2-adrenoceptors. Idazoxan`s diastereoisomers possess different relative selectivity for alpha2- pre- and postsynaptic receptors: (+)-idazoxan was 7-8 times more potent than (-)-idazoxan in inhibiting p-[3H]aminoclonidine binding, and 40 times more active in antagonizing clonidine at presynaptic level, indicating a better selectivity for alpha2-presynaptic sites. The pre- and postsynaptic alpha2-adrenoceptors have a different affinity for the two enantiomers of idazoxan. Although the stereoisomers are closely related structurally, (+)-idazoxan possesses a stronger affinity for presynaptic sites. This stereoselectivity was less evident for postsynaptic sites. In rats and dogs, both enantiomers antagonized the sympathoinhibitory effects of clonidine. In rats, (+)- idazoxan was 4-7 times more potent than (-)- idazoxan and 3-8 times more than (-)- idazoxan in dogs. A same order of potency was observed against the sedative effects of clonidine and azepexole in chicks, (+)- idazoxan being 8 times more potent than (-)- idazoxan. Although (+)- idazoxan was more potent than (-) idazoxan, binding studies revealed (-)- idazoxan to be more selective than (+)- idazoxan at central sites. It is concluded that (+)- idazoxan antagonizes both alpha-1 and alpha-2 adrenoceptors and (-)- idazoxan is selective for alpha-2 adrenoceptors. In the pithed rat, only (-)- idazoxan possesses both alpha-1 and alpha-2 agonistic effects.

Idazoxan is an alpha2 receptor antagonist which also shows activity at imidazoline I1 and I2 receptors and modulates the release of dopamine. Idazoxan was in phase II development in the US. Later the development of idazoxan for schizophrenia was discontinued. It was also in clinical trials for cognition disorders in United Kingdom, and was also discontinued. Idazoxan is used in scientific research as a tool for the study of alpha 2-adrenoceptors. Idazoxan`s diastereoisomers possess different relative selectivity for alpha2- pre- and postsynaptic receptors: ( )-idazoxan was 7-8 times more potent than (-)-idazoxan in inhibiting p-[3H]aminoclonidine binding, and 40 times more active in antagonizing clonidine at presynaptic level, indicating a better selectivity for alpha2-presynaptic sites. The pre- and postsynaptic alpha2-adrenoceptors have a different affinity for the two enantiomers of idazoxan. Although the stereoisomers are closely related structurally, ( )-idazoxan possesses a stronger affinity for presynaptic sites. This stereoselectivity was less evident for postsynaptic sites. In rats and dogs, both enantiomers antagonized the sympathoinhibitory effects of clonidine. In rats, ( )- idazoxan was 4-7 times more potent than (-)- idazoxan and 3-8 times more than (-)- idazoxan in dogs. A same order of potency was observed against the sedative effects of clonidine and azepexole in chicks, ( )- idazoxan being 8 times more potent than (-)- idazoxan. Although ( )- idazoxan was more potent than (-) idazoxan, binding studies revealed (-)- idazoxan to be more selective than ( )- idazoxan at central sites. It is concluded that ( )- idazoxan antagonizes both alpha-1 and alpha-2 adrenoceptors and (-)- idazoxan is selective for alpha-2 adrenoceptors. ( )- idazoxan is equipotent for antagonizing postsynaptic alpha-I and alpha-2 adrenoceptors. It is also a potent alpha-2 antagonist at presynaptic and central sites and is 4-8 times more potent than (-)- idazoxan but less selective.

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.