As all McGill medical students in Montreal did in the 1950’s, Mary and Philip Seeman took classes at the notorious Verdun hospital to see what catatonic schizophrenia was. It was Bedlam revisited. The noise, the screams, the wooden floor stench of urine, the frightening fixed postures of patients standing by each wall, and the silence of some catatonic patients, were indelibly imprinted on the minds of medical students.

Several years later in the 1960’s at Manhattan State Hospital, with its three thousand patients, most of whom had schizophrenia, Dr. Mary Seeman took care of a ward of one hundred patients with schizophrenia. But this time, although the building was old, the ward was quiet, patients cooperated, there were no immobile catatonic patients, and the ward sub-contracted successful work projects from New York. What happened?

What happened was that a new set of medicines, called “neuroleptics”, had arrived from France through Montreal, and the drugs were astonishingly effective for psychotic signs and symptoms. Now as a graduate student at Rockefeller University, working with the late Nobelist Dr. George Palade, Dr. Philip Seeman was encouraged by Mary to search for the mechanism of neuroleptic (or antipsychotic) action. If such a mechanism could be found, it might open the door to better treatment of psychosis.

After a twelve-year search for various possible targets for antipsychotics, Dr. Philip Seeman, now at the University of Toronto in 1975, discovered the “antipsychotic dopamine receptor”.  The discovery was made after Dr. Seeman realised that the concentration of therapeutic haloperidol in the patient’s spinal fluid was around 2 nanomolar. After having radio-haloperidol synthesised, it was then possible to detect the antipsychotic receptor at 2 nanomolar haloperidol. Because five dopamine receptors are known (four of which were cloned in the Seeman lab), the receptor is commonly known as the dopamine D2 receptor.

The D2 receptor is the common target for all the many antipsychotic drugs that block D2, including the traditional chlorpromazine and haloperidol, and the newer so-called atypical antipsychotics, and possibly the yet-to-be-marketed glutamate-type drugs.

At the same time, the D2 receptor is the main target for antiparkinson drugs that stimulate D2 to alleviate the slow motion, tremor, and rigidity of Parkinson’s disease.

For more information, see The Scientist, Volume 24, Issue 14, June 2010.