Capsules from One to Three

1 Pharmacotherapy in Psychiatry in the 19th Century. Historical events which led to effective pharmacological treatments in psychiatry began with Sertürner’s isolation of morphine from opium, in 1806. It continued with the discovery of lithium by Arfvedson, in 1817 and bromine by Balard, in 1825; the synthesis of chloral hydrate by Liebig, in 1832 and malonylurea (barbituric acid) by von Baeyer, in 1863; the isolation of hyoscine (scopolamine) from hyosciamine, in 1880; and the preparation of paraldehyde by Cervello, in 1882. It culminated with the synthesis of the phenothiazine ring by Bernthsen, in 1883, the propylamine (amphetamine) structure by Edeleano, in 1887, and the tricyclic iminodibenzyl structure by Thiele and Holzinger, in 1899. By the end of the 19th century, morphine combined with hyoscine was extensively used for the control of excitement, agitation and aggression; chloral hydrate and paraldehyde for calming and inducing sleep, and potassium bromide for relieving restlessness, anxiety and tension. The judicious use of these drugs provided the necessary means for day and night time sedation. It also allowed the replacement of physical restraint by pharmacological means.

2. Organic Chemistry and the Birth of the Pharmaceutical Industry. Development of organic chemistry began in 1858, with Friedrich August Kukulé’s demonstration that carbon is tetravalent and can link with itself to form long chains. It continued, in 1860, with Berthelot’s publication of his text on Organic Chemistry; and culminated in 1865 with Kekulé’s recognition that a chain of six carbon atoms can be closed into a “benzene” ring. Organic chemistry provided the necessary (scientific) means for J.R. Geigy and Alexander Clavel to found dye companies, in 1859, which were to become GEIGY and CIBA pharmaceuticals respectively; and for Jean Gaspar Dolfus and Friedrich Bayer to found companies, in 1862, which were to become Sandoz and Bayer pharmaceuticals, respectively.     

3. Neuropharmacology: Structural Basis and Conceptual Framework. Recognition of the structural basis and development of the conceptual framework in which neuropharmacology operates began, in the 1870s, with Golgi’s discovery of the silver nitrate method for staining nerve cells. Visualization of the finer structures of the brain, allowed Golgi to detect “multi-polar cells” in the cerebral cortex. This opened the path for Ramon y Cajal  to recognize that the “neuron” is the functional unit of the nervous system, in the 1880s, and for Sherrington to demonstrate, in the 1890s,  that the “synapse” is the functional site of transmission of nerve impulses from one neuron to another.