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Old drugs--new uses.

In 1949 Henri Laborit, a French surgeon, used the antihistamine promethazine to treat surgical shock in the belief that inhibition of the autonomic nervous system would prevent adverse cardiovascular responses to hypotension [1]. He found that it had some beneficial action and combined it with other drugs, in a so-called ‘lytic cocktail’, to prevent its adverse effects. The manufacturers of promethazine, Rhone–Poulenc, became interested and examined a range of phenothiazines that Paul Charpentier had synthesized as potential antihistamines [2]. A chlorinated derivative of promazine showed great promise in animal experiments, but when he tried it in patients undergoing surgery Laborit noticed that they became relaxed and unperturbed by the prospect of the operation. This serendipitous observation led him to persuade the psychiatrists at the Val de Grace military hospital in Paris to use it. The director of neuropsychiatry, Joseph Hamon, gave it to a patient with acute mania, who became calm.