A newly discovered neuroreceptor, unlike any known family of receptors, appears to be active in the physiological pathways underlying the development of depression. Preclinical studies with novel compounds indicate the potential new medications act directly on the recently found receptor to produce an antidepressant effect. The preliminary findings could lead to the development of new, unique medications for the treatment of depression.

The discovery of the receptor, the gene that codes for it, and the development of potential medications to modulate the receptor’s activity were announced last month in conjunction with the 30th Annual Society for Neuroscience meeting in New Orleans. Scientists with Synaptic Pharmaceuticals Corporation described the receptor, isolated earlier this year, as a "G protein-coupled receptor (GPCR)."

According to Synaptic researchers, GPCRs are a "superfamily" of receptors found in cell membranes, which are active in chemical signaling between cells. Within the superfamily of GPCRs are the serotonin, adrenergic, neuropeptide Y, and galanin families of receptors.

According to Kathleen P. Mullinix, Ph.D., president of Synaptic, the potential antidepressant medications the company is developing are receptor based rather than transporter based as is the case with all currently approved antidepressant medications.

Marie O’Connor, R.Ph., Ph.D., a clinical consulting pharmacologist in private practice, told Psychiatric News that this discovery could give the new drug candidates greater specificity and, therefore, potentially fewer side effects.

Mullinix said that Synaptic has completed testing of the new compounds in both cellular and animal models of depression. The company hopes to begin stage 3 clinical trials in early 2002. "A new neuroreceptor," said Mullinix, "that potentially plays a role in depression is exactly the kind of drug target we are seeking."

Mullinix noted that antidepressants now on the market do not appear to be active on the newly discovered target receptor. In addition, Synaptic’s antidepressant drug candidates do not appear to be active on the target transporter molecules of known antidepressant medications.

"This could imply," commented O’Connor, "that Synaptic’s molecules are working through a completely different biological pathway for depression.

"This is an exciting discovery," O’Connor concluded, "but it is a long way from producing a new medication with proven efficacy and a good safety profile."