35 Deniker’s hectic tour encompassed all of the major mental institutions in North America, and he was warmly received. His articulate presentations describing chlorpromazine-treated schizophrenic patients inspired and convinced many influential psychiatrists (2). By the end of 1953, SKF had supplied over 600 physicians with chlorpromazine, by far the largest group of investigators ever to test an investigational drug from SKF. But the dataset included only 104 psychiatric patients, whereas more than 1,000 patients had clearly established chlorpromazine’s efficacy as an antiemetic drug (2). On March 4, 1954, SKF submitted chlorpromazine to the Food and Drug Administration (FDA) for approval. The application contained 22 major clinical studies, of which 9 were antiemetic trials. The psychiatric data came from 6 investigators, including Lehmann in Montreal and Winkelman in Philadelphia (11, 13). On March 26, 1954, the FDA approved Thorazine® (SKF’s brand of chlorpromazine) for nausea and vomiting and in neuropsychiatry (2).
In 1931, Indian researchers isolated five alkaloids from the Rauwolfia root (1, 3). In 1952, chemists at the Swiss drug company Ciba successfully synthesized reserpine (Serpasil®), the alkaloid that accounts for about half of the pharmacologic activity of the Rauwolfia root, for use in hypertension (2, 3, 5). The Indian reports of hypertension and psychoses efficacy were published in English and available in the US. But American psychiatrists remained unaware of reserpine until Kline’s chance reading in The New York Times (1). After testing tablets of the whole Rauwolfia root and reserpine on himself, Kline treated over 700 psychiatric patients at Rockland State Hospital
The third pivotal event of 1953 was triggered by an article in the Sunday edition of The New York Times. On March 15, 1953, Nathan Kline, an American psychiatrist, was reading The New York Times when a report from India caught his eye. R. A. Hakim had been awarded a gold medal at a medical conference in Bombay for his presentation of a paper on the cure of schizophrenia (14). There was no drug in Western medicine that cured schizophrenia, so Kline was intrigued. Hakim’s potion consisted of a half-dozen herbs, but the main ingredient was Rauwolfia serpentina, a shrub with red blossoms that grows wild in many parts of India (1, 3, 14, 15). For hundreds of years, Rauwolfia had been a common household remedy for insect and snake bites, insomnia, intestinal diseases, and to facilitate childbirth (1, 14, 16). It had also been used for fevers, to induce sleep in children, and as a cure for insanity (15, 16). In the 1930s and 1940s, several Indian investigators reported that Rauwolfia serpentina was an effective treatment for hypertension (1, 3). Tablets made from the dried Rauwolfia root were in “such unprecedented popularity” that nearly every patient with high blood pressure in India had used it (16).
In the Public Domain
Reserpine
An advertisement from the early 1960s for Thorazine®, Smith, Kline & French (SKF) Laboratories’ brand of chlorpromazine
Reprinted from The Pharmacologist • September 2016