by Tom Ray

The completion of the human genome has revealed the tremendous complexity of the chemical signaling pathways in our bodies. There appear to be over three hundred different kinds of receptors expressed in the brain.

To understand how variations in the activities of these chemical signaling pathways can combine to produce mental states and mental disorders, we need to develop an empirical understanding of the influence of these systems on mental states. This understanding must include interactions between different chemical signaling systems, as well as the role of individual systems. The cloning and development of receptor binding and functional assays for a large number of receptors is opening a new "post-genome" era of pharmacology, which permits us to look at the global effects of drugs on the brain and body.

The National Institute of Mental Health set up a Psychoactive Drug Screening Program (PDSP) using this new post-genome approach. PDSP is the "supercomputer" of pharmacology. It is a facility, still under development, that allows us to screen drugs against the entire human "receptome" (all receptors in the human body).

It is a facility like a supercomputer, that is so massive and expensive, that in this case, only one can exist. Therefore NIMH has set up one such facility, and makes its screening services available to researchers, like the supercomputers at the National Center for Supercomputing Applications (NCSA).

A few years ago, it was a very difficult task to screen a drug against a single receptor, to deterine if the drug binds to the receptor, and if so, what it does there (blocks, activates or de-activates). In the past, pharmacologists were like the blind men and the elephant only able to look at one or a few parts of the chemical system. Now for the first time it is becoming possible to look at the whole system.