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Everhardus. J. Ariens, Ph.D.

Adapted from the Dutch-language Wikipedia with the assistance and permission of Evert Ariens:

Everhardus Jacobus Ariens was a member of an important Dutch brick manufacturing family and a Dutch pharmacologist and professor at the Katholieke Universiteit Nijmegen (Radboud Universiteit Nijmegen today). He made important contributions to the understanding of the function of receptors and the mathematical description of ligand-receptor interactions (receptor theory). In addition, Ariens was the initiator for the collection of stereochemistry in drug development and has pioneered the development of enantiomerically pure drugs.

Everhardus Ariens was born on January 29, 1918 in Wijk bil Duurstede, the Netherlands, and grew up as the sixth of ten children. After a temporary stay in a boarding school, he went to the pre academic school (HBS) in Wageningen in 1935. Then he began studying chemistry at the University of Utrecht, from which he graduated in 1942, although his preference was actually biology. His studies were interrupted by the Second World War. After his refusal to sign a declaration of loyalty to the German Reich, he escaped from the territories occupied by Germany via Switzerland, France and England, and he found asylum with the U.S. Army. [1] He completed his unfinished study of medicine after the second world war, and received a degree in 1948 [2].

After the Second World War, he conducted research in the laboratory of Prof. UG Bijlsma in the area of adrenergic substances and received a double doctorate in the fields of chemistry and in medicine on the same day in 1950. In 1951, Ariens moved to Nijmegen, having been established at the local Catholic University in the Department of Pharmacology. From 1954 until his retirement, he worked as a professor.

Based on his dissertation, he developed a method for the quantification of pharmacological effects resulting from ligand-receptor interactions. To this end he introduced the concepts of affinity and intrinsic activity. [3] With the help of these terms he could describe the behaviour of agonists and antagonists and the dual agonist / antagonist behaviour of partial agonists. An important contribution made by Ariens was the establishment of quick and reproducible experiments on isolated organs rather than in living animals, which could quantitate the affinity and intrinsic activity of test substances.

The term antagonist was originally coined to describe different profiles of drug effects. The biochemical definition of a receptor antagonist was introduced by Ariens in the 1950s. The current accepted definition of receptor antagonist is based on the receptor occupancy model. It narrows the definition of antagonism to consider only those compounds with opposing activities at a single receptor. Agonists were thought to turn "on" a single cellular response by binding to the receptor, thus initiating a biochemical mechanism for change within a cell. Antagonists were thought to turn "off" that response by 'blocking' the receptor from the agonist. This definition also remains in use for physiological antagonists, substances that have opposing physiological actions, but act at different receptors. For example, histamine lowers arterial pressure through vasodilation at the histamine H1 receptor, while adrenaline raises arterial pressure through vasoconstriction mediated by β-adrenergic receptor activation.

E.J. Ariens was also active in the field of structure-activity relationships (SAR), a branch of medicinal chemistry. With the provocative statement that commonly used racemic drugs were 50% contaminated, [4] he triggered a debate among pharmacologists and medicinal chemists and alerted the drug approval agencies. Ariens work was therefore the key precursor for the targeted development of enantiomerically pure drugs. Another of his theories, surrounded his controversial view view that drug metabolism is wasteful, and he called for the development of metabolism-resistant drugs. He also continued in the tradition of Dutch pharmacologists and fought against quackery. [1]

Everhardus Ariens was awarded the Purkinje Medal in 1963 at the second International Congress of Pharmacology in Prague. He also received the Dr. Saal van Zwanenberg Prize (1972), the Poulsson Medal of the Norwegian Society of Pharmacology (1973), the Scheele Medal (1974), the Schmiedeberg-Medal (1980) and the Smissman Award of the American Chemical Society (1985). He was also awarded honorary doctorates by the universities Universidade Luterana do Brasil, Christian-Albrechts-University Kiel, University of Paris-Sud and Università degli Studi di Camerino. He posthumously received an honorary doctorate on March 22,2002 from the Ohio State University [2].

Professor Ariens was knighted by H.M. the Queen of the Netherlands to Ridder in de Orde van de Nederlandse Leeuw, and also received the following awards: Honorary citizen of the State of Texas; Member of the Royal Academy of Science of the Netherlands; Deutsche Akad. der Naturforscher Leopoldina; Acad. Royale de Médicine de Belgique; Kon. Acad. voor Geneeskunde; Kon. Acad. voor Geneeskunde. He was a corresponding member of German Pharmacological Society, an honorary member of Soc. Italiana di Scienze Farmaceutiche, Asoc. de Quimicos-Spanje, Dutch Pharmacological Society, Ac. of Pharmaceutical Sciences, South African Pharmacological Society, Kon. Ned. Chemische Ver. E.J. Professor Ariens passed away on March 3, 2002 in Nijmegen.

[1] H. Timmerman, DD Breimer: Everhardus Jacobus Ariens. Nederlandse Akademie van Wetenschappen Koninglijke, www.knaw.nl/publicaties/pdf/20061074_1.pdf

[2] P. N. Patil: Everhardus J. Ariens (1918-2002). A tribute. In: Trends in Pharmacological Sciences. Volume 23, 2002, p. 344-345.

[3] Ariens EJ, van Rossum JM, Simonis AM: Affinity, intrinsic activity and drug interactions. In: Pharmacol. Rev.. 9, No. 2, June 1957, p. 218-236. PMID 13,465,302th

[4] Ariens EJ: Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology. In: Eur J. Clin. Pharmacol .. 26, No. 6, 1984, p. 663-668. PMID 6092093

Books: E. J. Ariens: Molecular Pharmacology. Elsevier Science & Technology Books, San Diego, USA, 1967, ISBN 0120604019

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