Dysregulation of cholinergic neurotransmission through muscarinic receptors, particularly the M1 and M4 subtypes, has been implicated in the pathophysiology of schizophrenia. Muscarinic M4 receptor agonists and positive allosteric modulators (PAMs) have demonstrated the ability to modulate the disrupted neural circuits associated with this disorder.

Yichang Humanwell Pharmaceutical Co. Ltd. has discovered nociceptin receptor (OPRL1; KOR3; ORL1) agonists reported to be useful for the treatment of pain.

Researchers from Iama Therapeutics Srl and the Italian Institute of Technology have prepared and tested solute carrier family 12 member 2 (SLC12A2; NKCC1) inhibitors reported to be useful for the treatment of complex regional pain syndromes, Alzheimer’s disease, Down syndrome, glioma, Rett syndrome, temporal lobe epilepsy, traumatic brain injury and obsessive-compulsive disorder.

Muna Therapeutics ApS has synthesized triggering receptor expressed on myeloid cells 2 (TREM2) agonists reported to be useful for the treatment of Alzheimer’s disease, inflammatory bowel disease, metabolic syndrome, multiple sclerosis, obesity, Parkinson’s disease, rheumatoid arthritis and stroke, among others.