Amisulpride, a benzamide derivative, shows a unique therapeutic profile being atypical antipsychotic. At low doses, it enhances dopaminergic neurotransmission by preferentially blocking presynaptic dopamine D2/D3 autoreceptors. At higher doses, amisupride antagonises postsynaptic dopamine D2 and D3 receptors, preferentially in the limbic system rather than the striatum, thereby reducing dopaminergic transmission. In addition its antagonism at serotonin 5-HT7 receptors likely underlies the antidepressant actions. Amisulpride is approved for clinical use in treating schizophrenia in a number of European countries and also for treating dysthymia, a mild form of depression, in Italy.

Cenicriviroc (also referred to as TBR-652 and TAK-652) is an orally active, potent inhibitor of ligand binding to C-C chemokine receptor type 2 (CCR2) and C-C chemokine receptor type 5 (CCR5). Cenicriviroc does not inhibit ligand binding to CCR1 (an alternative target of CCR5 ligands). The mean half-life in healthy volunteers is 35 to 40 hours, which allows daily dosing of the drug. Due to its CCR5 blocking activity, Cenicriviroc has initially been tested as a drug against CCR5-tropic HIV infection. In a double-blind placebo-controlled trial involving 54 HIV infected participants, Cenicriviroc monotherapy at different doses (25, 50, 75, 100, or 150 mg) led to a dose-dependent reduction in HIV-1 RNA levels and concomitant increases in circulating levels of the CCR2 ligand monocyte chemoattractant protein 1 (MCP-1, or CCL2), suggesting potent CCR2 and CCR5 inhibition in vivo. According to clinical trials, Cenicriviroc is a very safe drug with a wide therapeutic range and fairly low pharmacokinetic variability. In animal models of liver diseases, Cenicriviroc potently inhibits macrophage accumulation in the liver and ameliorates fibrosis. In a phase 2b clinical trial on 289 patients with NASH and fibrosis, Cenicriviroc consistently demonstrated liver fibrosis improvement after 1 year of therapy and had an excellent safety profile.

MK-0812 is a potent and selective CCR2 antagonist, which was developed by Merck. This drug has entered clinical trials for both rheumatoid arthritis and multiple sclerosis. However, the rheumatoid arthritis trial was terminated because of lack of favorable outcomes when MK-0812 failed to show any early clinical improvement. The outcome of the multiple sclerosis trial of MK-0812 also had negative outcomes.

INCB-8761 (PF-4136309) is an orally available human chemokine receptor 2 (CCR2) antagonist with potential immunomodulating and antineoplastic activities. Upon oral administration, CCR2 antagonist INCB-8761 specifically binds to CCR2 and prevents binding of the endothelium-derived chemokine ligand CLL2 (monocyte chemoattractant protein-1 or MCP1) to its receptor CCR2, which may result in inhibition of CCR2 activation and signal transduction. This may inhibit inflammatory processes as well as angiogenesis, tumor cell migration, and tumor cell proliferation. INCB-8761 is a potent CCR2 antagonist with high selectivity, weak hERG activity, high free fraction in protein binding, and an excellent in vitro and in vivo ADMET (ADME and toxicology) profile. INCB-8761 entered human clinical trials. It is in phase I/II clinical trials for pancreatic cancer.

TAK-779 is a selective antagonist of CCR5 receptor, which was initially developed by Takeda for the treatment of HIV infection. However, the development was terminated due to poor oral bioavailability. Also, TAK-779 demonstrated the ability to protect the brain against focal cerebral ischemia in mice.

UCB35625 is a potential inhibitor of chemokine/eosinophil interactions. UCB35625 is a trans-isomer of a compound J113863, which was originally identified by scientists at Banyu Pharmaceutical Company as a candidate small molecule chemokine receptor antagonist. UCB35625 initially identified as CCR1 and CCR3 antagonists also bind to CCR2 and CCR5 and act as full agonist, partial agonist or antagonist according to the nature of the receptor and the signaling pathway investigated. UCB35625 shows promise as a lead compound for the design of future therapeutics, which may be of use in the treatment of allergic inflammatory diseases such as asthma and also the blockade of viral entry by HIV strains that utilize CCR3.

J 113863 is a potent and high selective CKR-1 (CCR1) and CKR-3 (CCR3) chemokine receptor antagonist, which is also behaved as a full agonist of CCR2 and as a very partial agonist of CCR5. This compound was investigated for the treatment of multiple sclerosis and rheumatoid arthritis, but the status of these studies are not known.