Laborit

Promethazine employed as a preanesthetic calming drug by Laborit. 

Laborit replaces promethazine with chlorpromazine for pre-surgical anesthesia. 

The efforts made by the French surgeon Laborit to find a safer anesthetic technique and to prevent surgical shock. 

Of special interest is the contribution made by Henri Laborit, who had worked as an army surgeon during the Second World War and who, under the influence of his war experiences, devoted himself in subsequent years primarily to the problem of shock. 

Laborit obtained 4560 RP in June 1951 and soon recognized the advantages of the new substance it lessened the anxiety felt by patients prior to surgery, diminished surgical stress and made it possible to simplify the mixture of medicaments used by Laborit the so-called lytic cocktails. Furthermore, the compound had a low toxicity and consequently could be used in a broader dosage rather than, for example, curare. 

Under the effect of chlorpromazine, as 4560 RP was later to be named, patients did not lose consciousness but merely became sleepy and uninterested in everything going on around them and being done to them (Laborit et ti/.. 1952). Laborit and co-workers postulated that this strange central action suggested the use of chlorpromazine in psychiatry, e.g. in sleep therapy, where... 

Chlorpromazine s (CPZ) efficacy was discovered primarily by chance in exploratory clinical trials after it had been initially synthesized as an antihistamine. Its discovery, however, was not entirely fortuitous, because it was chosen for human investigation since it was mildly sedating. The concept of an antipsychotic, however, was unknown. CPZ s sedative properties then led the French anesthesiologist and surgeon Henri Laborit to use it in a lytic cocktail to reduce autonomic response with surgical stress (1). He also persuaded many clinicians to try it for the treatment of a wide variety of other disorders. In this context, he encouraged John Delay and Pierre Deniker (1952), who then administered CPZ to schizophrenic patients. The rest is history ( 2, 3). 

Like many of his contemporaries, Claude Rifat was drawn to experimentation with psychoactive drugs, but he soon learned that he could accomplish the effects he sought without them. Through his contact with the French psychobiologist Henri Laborit, he was inspired to elaborate models of these transformations that involve the natural neuromodulator serotonin, just as I will do in chapter 7. Claude Rifat s life has led him back to the east, but now it is the extreme orient that he calls home. There he has felt freer to pursue his self-observation based scientific inquiries and develop his personal, social, and ecological ideals. 

Laborit in the early 1950s is credited with the observation that chlorpromazine had a "calming effect in disturbed schizophrenic patients and since that time psychopharmacologists have sought to explain the mechanism of action of neuroleptic drugs. Carlsson and Linquist in 1963 demonstrated a link between the therapeutic effects of the phenothiazine neuroleptics and an inhibition of dopamine receptor function. This led to... 

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