Capsules Seven to Nine

7. Neurochemistry of neuronal transmission: Early development. Research which led to the detection of the molecular substrate of neuronal transmission began with Elliott’s discovery of “sympathin” release at “sympathetic” nerve endings, in 1904. It continued with Dale’s demonstration of acetylcholine (ACh) release at “parasympathetic” nerve endings, in 1914; and culminated in Otto Loewi’s recognition of the changes in adjacent cells to the ACh release in  1921. Research shifted from the periphery to the brain with the development of chromatography. With the employment of the new methodology in the late 1930s Quastel and his associates demonstrated the presence of the necessary enzymes for ACh synthesis in the cerebral cortex; Stedman and Stedman isolated ACh from brain homogenates, and Pugh and Quastel, and independently Blaschko and his associates detected the presence of the enzyme that was to become known as monoamine oxidase in the brain.

8. Drug regulation in the USA. Drug regulation in the United States began, in 1906, with the first Pure Food and Drug Act. An amendment to the Act, in 1912, authorized the government to prosecute any false therapeutic claims if fraudulent intent was involved. After the sulfanilamide crisis, in 1937, the Federal Food and Cosmetic Act, which obliged manufacturers to report their findings on safety to the FDA before marketing their products, was enacted, in 1938. In 1951, the Humphrey – Durham amendment separated prescription and non-prescription (over–the– counter) drugs. In, 1952, the Delaney Committee recommended the completion of “adequate safety studies” before the release of any substance for clinical use. In 1962, after the thalidomide crisis, the Kefauver-Harris Drug Amendment stipulated that both the effectiveness and the safety of new drugs must be determined before their introduction into clinical use; that the distribution and the use of investigational drugs must be controlled; that drugs must be produced with sound manufacturing practices; and that prescription drug advertising must be FDA approved.  

9. Pharmacologically induced fever. Pharmacologically induced fever with the administration of sodium nucleinate in the treatment of cerebral syphilis was reported by Lundvell, in 1907. Prior to the use of sodium nucleinate, Wagner-Jauregg used typhoid vaccine to induce fever in the treatment of general paralysis (paresis) of the insane. Fever therapy with malarial blood was first used in cerebral syphilis by Wagner Jauregg in 1917. For his contributions to the treatment of GPI with malarial blood Wagner-Jauregg was awarded the Nobel Prize in 1927.