Synaptic Pharmaceutical Scientists Use 'Biogenomics' to Find Elusive Receptors For Trace Amine Neurotransmitters
PARAMUS, N.J., July 18 /PRNewswire/ -- Scientists at Synaptic Pharmaceutical Corporation (Nasdaq: SNAP - news) have discovered a family of G protein-coupled receptors (GPCRs) for a group of natural (endogenous) chemical messengers known as trace amines, it was reported in the July 17 Proceedings of the National Academy of Sciences online Early Edition (http://www.pnas.org). Trace amines have long been known to be associated with various neurological disorders, such as depression and schizophrenia, however, receptors for trace amines could not be found, until now. The Company credits its ``biogenomics'' technology, which combines biology and genomics into a unified drug discovery approach, with the breakthrough. The discovery will also be published in the July 31 print version of Proceedings of the National Academy of Sciences.
A research team led by Beth Borowsky, Ph.D., found fifteen related receptors in three species of mammals, including four receptors that are expressed in humans. The authors of the paper reported that finding ``such a large family of highly related receptors'' was ``unexpected.'' In the human brain, three of the receptors were found to be concentrated in an area known to play a role in regulating mood. Also, the trace amine genes are located on a chromosome close to a susceptibility locus for schizophrenia. ``Thus, it will be important to delineate the role of receptors in the etiology and treatment of schizophrenia,'' the authors wrote.
Trace amines, which include tyramine, tryptamine and beta-phenylethylamine, are closely related chemically to the well-known neurotransmitters serotonin, dopamine and norepinephrine, the so-called biogenic amines. This close relationship and evidence that trace amine levels are abnormal in certain psychological disorders have led researchers to posit that trace amines are important biological signals.
``We've long suspected that trace amines are important neurotransmitters,'' said Borowsky, ``but without receptors we couldn't prove it. Now we have the tools to find out what biological role trace amines play.''
On July 9 at the Gordon Research Conference on Catecholamines at the Proctor Academy in Andover, New Hampshire, Theresa Branchek, Ph.D., vice president for research, reported the Company has synthesized several compounds that act specifically on trace amine receptors and will shortly begin evaluating them in animal models of depression and schizophrenia. ``We've expanded our drug discovery efforts to include this new class of G protein-coupled receptors,'' Branchek said. ``We think the similarities between trace amines and biogenic amines make trace amine receptors attractive targets for designing new drugs. These new treatments hold promise for a broad spectrum of neurologic and psychiatric diseases.''
The trace amine receptor discovery is an outgrowth of Synaptic's extensive effort to discover and characterize serotonin receptors. Of the fourteen known serotonin receptors, Synaptic researchers have discovered seven. The close relationship between serotonin and trace amine receptors contributed to the discovery. The receptors and transporters for serotonin, dopamine and norepinephrine are the target for a number of blockbuster drugs for the treatment of depression, psychosis, heart disease, migraine headache and histamine.
Kathleen P. Mullinix, Ph.D., chairman, president and chief executive officer said, ``Our discovery of trace amine receptors shows the power of integrating biology and genomics into a single, unified drug discovery approach. Synaptic's focused GPCR genomics effort led us to the receptors; biology told us what to do. We believe our approach, which we call 'biogenomics,' will be the key to unlocking the full potential of the GPCR information flowing from the human genome project.''
Synaptic Pharmaceutical Corporation is a drug discovery company focused on GPCR receptors. The Company is using its large portfolio of patented GPCR targets to design improved drugs and to map biological pathways that may offer new ways to treat diseases. As of July 18, the Company is collaborating with Grunenthal GmbH on discovering compounds for the alleviation of pain and with Kissei Pharmaceutical Co., Ltd. in a functional genomics collaboration to identify novel G protein-coupled receptors that can provide new drug discovery targets for Kissei. For more information on the Company, please visit our web site at synapticcorp.com. |
