Solomon Snyder, M.D., a professor of neuroscience, pharmacology, and psychiatry at the Johns Hopkins University School of Medicine in Baltimore, is well known and highly respected in the converging worlds of neuroscience, pharmacology, and psychiatry. In fact, Joseph Coyle, M.D., chair of psychiatry at Harvard University Medical School in Boston, contends that he "is the most creative scientist in psychiatry today" and that "his research has had a huge impact on drug development."

During the 1960s and 1970s, for instance, Snyder and his team identified the brain’s dopamine and opiate receptors and then went on to define the role of several endorphins as neurotransmitters. Since then they’ve made other provocative discoveries as well—for instance, that gases can serve as neurotransmitters, and that not just neurons, but glial cells in the brain, can crank out neurotransmitters.

Snyder described these more recent findings at APA’s annual meeting in Chicago in May, where he was a special guest lecturer and received APA’s first Marmor Award.

Back in the early 1920s a chemical was found that transmits messages between nerves. It was acetylcholine. For many years acetylcholine remained the only known neurotransmitter. Then came the identification of a second one—norepinephrine—followed by two more—dopamine and serotonin. And during the 1960s some amino acids, notably glutamate, also joined the ranks, as did a few years later several peptides (endorphins), thanks to the efforts of Snyder and his colleagues.

Then in 1987 some researchers reported that the gas nitric oxide plays a major role in blood-vessel relaxation. Snyder and his coworkers then wondered whether nitric oxide might also function in some capacity in the brain. And indeed it does, they reported in 1989—it works as a neurotransmitter. Both findings prompted Science magazine in 1992 to dub nitric oxide "molecule of the year."

As a gas, nitric oxide flunked the first rule of neurotransmitters—it cannot be stored in the little vesicles at the ends of nerves because it would leak out of them. So, every time a nerve wants to release nitric oxide, it has to make new nitric oxide. So how does it do it? One of Snyder’s coworkers found that glutamate, acting through one of its receptors, activates the formation of nitric oxide, and does so in a matter of seconds. One would need such speedy manufacture, Snyder explained, if a gas were going to transmit messages between nerves.

After this discovery, one of Snyder’s colleagues suggested that other gases might work as nerve transmitters in the brain. He proposed carbon monoxide as a candidate. "Carbon monoxide?," Snyder exclaimed. "Why, carbon monoxide can kill you." Nonetheless, they pursued this unlikely possibility, and lo and behold, they found that carbon monoxide not only resides in discrete neuronal populations in the brain, but also works as a neurotransmitter, at least in the peripheral nervous system.

Yet an even more bizarre neurotransmitter than nitric oxide and carbon monoxide made its debut on the scene. It was the amino acid D-serine, and Snyder and his colleagues found it not in brain neurons, but in brain glial cells. It appears to help glutamate function as a neurotransmitter in nerve cells.

Indeed, all the important drugs currently available in psychiatry act through one neurotransmitter or another, Snyder pointed out. For example, a major mechanism of the SSRI antidepressants is inhibition of neurotransmitter reuptake in nerve terminals. So the latest findings coming out of his lab, Snyder anticipates, may also lead to some valuable new drugs for psychiatry.

For instance, now that nitric oxide has been found to be a major determinant of blood pressure, drugs that act on it are already under development. Such drugs might likewise prove helpful in treating excessive male aggression or excessive male sexuality, since Snyder and his colleagues have found, in mice, that the normal function of nitric oxide in the brain—at least in males—seems to be to dampen aggression and sexual urges.

As for D-serine, it is made by a single enzyme, so drugs could easily be designed to act against this enzyme. Such drugs might then prove to counter Alzheimer’s, Parkinson’s, Huntington’s, or other neurodegenerative diseases, because D-serine helps glutamate function as a neurotransmitter and because there is some evidence that excessive glutamate stimulation in the brain may be a culprit in these disorders.

In fact, giving D-serine itself as a drug might benefit persons with schizophrenia because psychosis caused by PCP (angel dust) blocks nerve receptors for glutamate and because D-serine, as glutamate’s neurotransmitter partner, might get nerve receptors for glutamate activated again. A trial conducted in Taiwan suggested that D-serine administration improves cognition and reduces negative symptoms in patients with schizophrenia. Coyle and his colleagues are now trying to get approval from the Food and Drug Administration to conduct a similar clinical trial in the United States.

Meanwhile, Snyder and his team are continuing to "cook up a storm" in their lab, as Snyder put it. What titillating discovery will emerge next? Zinc as a neurotransmitter is a possibility, Snyder said. He and his colleagues have found that this metallic element is especially prevalent in the hippocampus of the brain, that it is concentrated in the same nerve synaptic vesicles as the neurotransmitter glutamate, and that excess zinc, like excess glutamate, can be toxic to brain neurons. So, "the thinking is that maybe zinc and glutamate are released together as co-neurotransmitters," Snyder said.