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Scientists consider receptors--which are specially tailored protein molecules--and the substances that bind to them to be the critical junction in the ongoing chemical processes that underlie thinking, feeling, dreaming and remembering. For an electrical signal to travel from neuron to neuron in the brain, it must cross a minuscule gap, the synapse, between them. A number of different chemical messengers known as neurotransmitters ferry the signal across the synapse and then lock on to receptors that lie on the membrane of the next nerve cell in line.
Some neurotransmitters induce other neurons to fire; others dampen neuron activity. In either case, once the chemical locks on to the receptor, it sets in motion a cascade of chemical events in the receiving cell. This ongoing dance of neurotransmitters and receptors is the intricate code that brain cells use to communicate with one another.
Many psychoactive drugs--including opiates, the Valium-type compounds and angel dust--mimic the action of neurotransmitters by binding to particular receptors and influencing the neuron's firing. Pharmacologists have acquired the tools to screen new drugs quickly, testing their affinity for particular receptors by cloning, or duplicating, the receptors and then designing molecules that bind to them. So refined are the new techniques that scientists now know of 14 different receptors for serotonin, the ubiquitous chemical messenger that plays a critical role in sleep, mood, depression and anxiety. They have also discerned five different receptor subtypes for dopamine, a neurotransmitter thought to be involved in schizophrenia. By formulating compounds that selectively bind to particular dopamine receptors, for example, drug designers can craft schizophrenia drugs that curb hallucinations without triggering disabling Parkinsonian symptoms.
The development of drugs for schizophrenia, one of the most perplexing and devastating of all mental illnesses, was an early success story. After several decades as a hopeless research backwater, the schizophrenia field was reborn in 1989, when the U.S. Food and Drug Administration approved a remarkable drug, clozapine (brand name: Clozaril). Made by the Swiss pharmaceutical firm Sandoz, Clozaril was aimed at patients who did not benefit from other drugs. While traditional antipsychotic drugs such as chlorpromazine (Thorazine) and haloperidol (Haldol) work by blocking dopamine receptors, Clozaril appears to bind to serotonin receptors as well. "It is what we call a dirty drug," says Mount Sinai's Davis. "It probably binds to a whole bunch of receptors. We used to think that was a bad thing. Now we think that's maybe a good thing." Perhaps because of its affinity for serotonin receptors, Clozaril is largely free of the Parkinsonian side effects (the "Thorazine shuffle" and so on) that plague the classic antipsychotic drugs. It was also the first drug to ameliorate symptoms of schizophrenia that are resistant to other drugs. But Clozaril has a major drawback: a life-threatening side effect called agranulocytosis, a drastic drop in white blood cells that requires patients to undergo expensive weekly blood monitoring.