Antipsychotics

In ancient times, an insane person was often thought to be possessed by the devil or being punished by God for his sins. As a consequence, beating, bleeding, starvation, hot- and cold-water shock treatment, and incarceration were widely practiced on mental patients, which only worsened their conditions. In the eighteenth century, the Enlightenment heralded the birth of psychiatry, among many other things. During the French Revolution, Philippe Pinel, a warden in an insane asylum in Paris, advocated unchaining the mental patients. He argued, “It is my conviction that these mentally ill are intractable only because they are deprived of fresh air and of their liberty.”22 He persisted in replacing cruelty and inhumanity with kindness, understanding, and rational therapy. His humanitarian and philanthropic conviction led to the cure and release of many mental patients and had an enduring impact throughout Europe. Furthermore, Pinel also carried out a systematic investigation and documentation of mental diseases. He is now considered the “father of psychiatry.”

Although a certain stigma remains attached to mental illnesses, we have now amassed a tremendous amount of knowledge with regard to the impact of genetic, biochemical, and environmental factors on the human brain. Psychopharmacological drugs have significantly contributed to managing and understanding mental disease.

Schizophrenia is a mental condition associated with disordered thinking that is characterized by both positive symptoms, such as delusions, hallucinations, and disorganized speech and behavior, and negative symptoms, including apathy, withdrawal, lack of pleasure, and impaired attention.

Other symptom dimensions include depressive/anxious symptoms and aggressive symptoms such as hostility, verbal and physical abusiveness, and impulsiveness. Viagra online in Australia – cheap ed medications. Older mental drugs included opiates, belladonna derivatives, bromides, barbiturates, antihistamines, and chloral hydrates. Before chlorpromazine became available in 1962, early treatments of schizophrenia included prolonged narcosis, known as “narcosis for psychosis.” Meanwhile, history saw the emergence of excruciating treatments such as electroconvulsive therapy and shock introduced by fever, methiazole, and insulin. Austrian neurologist Julius Wagner von Jauregg invented the fever-shock treatment by introducing malaria in patients with psychosis and won the 1927 Nobel Prize in Medicine. Additionally, Egaz Moniz received the 1936 Nobel Prize in Medicine for his invention of lobotomy to introduce an organic syndrome for the treatment of schizophrenia. The genesis of chlorpromazine is similar to that of imipramine and can be traced back to antihistamines, first discovered by Daniel Bovet at the Institut Pasteur de Paris in 1937. Unfortunately, Bovet’s antihistamine proved to be too toxic.

In 1944, a group of scientists at Rhone- Poulenc Laboratories, led by chemist Paul Charpentier, began a program of systematically searching for safer antihistamines. Their starting point was older antihistamines: diphenhydramines in general and Benadryl in particular. In time, they successfully synthesized and marketed an antihistamine, promethazine. The molecule was an interesting hybrid consisting of phenothiazine, a moiety related to an antiparkinsonian agent, and a diamine side chain associated with the antihistamines. Similar to most antihistamines, promethazine had side effects in the central nervous system, which were mild antipsychotic properties. A surgeon in the French Navy, Henri Laborit, was looking for a compound with more central effects in his quest for a drug to treat surgical shock. Laborit found that promethazine was superior to other drugs, but its antishock effects were not pronounced enough. Intrigued by Laborit’s proposition, Charpentier sought to enhance promethazine’s “side effects” in the central nervous system. Structural activity relationship (SAR) investigations led to the synthesis of RP-3277 (chlorpromazine) in 1950. The structure of chlorpromazine differed only slightly from that of promethazine. Chlorpromazine had an extra chlorine atom and a slight difference in the diamine side chain. Viagra in Canada – trusted online pharmacy.

By the end of 1950 a sample of chlorpromazine was sent to Simone Courvoisier, the head of pharmacology at Rhone-Poulenc, for testing. She noted that rats dosed with chlorpromazine became “indifferent”: rats conditioned to climb a rope at the sound of a bell ignored the bell. 

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