This substance was destined to become a real symbol of psychiatry. No matter how many names doctors and patients came up with for it. Bringing salvation to tens of thousands of patients, he managed to be a tool of punitive psychiatry. His mention of the Internet and jokes has become commonplace for a long time. The hero of our today's story in the joint column "neuromolecules" of the portal "Neuronews" with the Institute of Bioorganic Chemistry of the Russian Academy of Sciences - haloperidol.
As we remember, the discovery of chlorpromazine has revolutionized psychiatry. But it was not him who was destined to become the most famous and effective neuroleptic.
The "other" analgesic
The pioneering father of haloperidol, Paul Janssen, is a special figure in the world of pharmaceuticals in the mid-20th century and probably the most famous Belgian in science. This legendary chemist and talented entrepreneur organized his laboratory in a hangar in 1953, which he rented from his father. His team consisted of only five people, the eldest of whom was 27 years old. Paul himself had only a bachelor's degree by then, but his scientific flair and high efficiency had made his business. During his first three years of work, his laboratory synthesized and tested 800 different compounds, eight of which eventually found their application in medicine! Unsurpassed result.
By the time haloperidol opened, Janssen had already led a group of 50 employees. Obtaining and bringing to market a few years earlier the powerful opioid analgesic dextromoramide brought him a well-deserved reputation and extensive scientific ties. A conversation with Professor Arnold Beckett led Janssen to the idea of creating a new powerful analgesic through a chemical modification of meperidine (better known as demerol), an opioid that is about 10 times weaker than morphine in its analgesic properties. The serial build-up of the lateral chain of the meperidine molecule led to the synthesis of a whole series of butyrophenones. The 44th of them was synthesized on February 11, 1958, by chemist Bert Germanz. This variant was called R 1625 and almost immediately went to be tested on mice.
To make the process as cheap as possible, Janssen evaluated the entire spectrum of the substance in two simple tests. In the first test, the diameter of the pupil was measured in mice that received the dose of the drug. This gave an idea of the cholinergic activity of the compound. Then, the mouse was placed on a plate heated up to 55°C, and it was considered how often it licked the legs, evaluating the analgesic and neuroleptic effects of the substance. After administration of R1625 in a dose of 10 mg/kg, the diameter of the mouse pupil did not change in any way. But when she was put on a hot plate, she just didn't care. Scientists - the people are patient, but even their perseverance was enough only for 3 hours of waiting. During this time the calm mouse did not give any signs of displeasure, but a normal animal in such a situation licked its feet every 30 seconds!
Despite the intriguing results, the first human test of the substance is difficult to call successful. Five weeks after the synthesis of R1625, a dose of 2 mg was administered to several alcoholics suffering from the most severe form of white fever. Strange as it may seem, the doctor was unable to notice any effect other than a brief decrease in pressure. However, the trials continued and all subsequent applications of the drug ended in complete success. The new substance calmed the violent, dispelled hallucinations and suppressed psychomotor agitation. A year later, it got its usual name - haloperidol - and the beginning of its triumphal procession through the psychotherapeutic clinics of the world.
to be continued in the next part