A Brief History of Great Discoveries in Pharmacology: In Celebration of the Centennial Anniversary of the Founding of the American Society of Pharmacology and Experimental Therapeutics

Rubin, Ronald P.

doi:10.1124/pr.107.70102

Cited by 75 publications

(50 citation statements)

References 179 publications

(103 reference statements)

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“…In that same year, George Widmer Thorn and P H Forsham were the first to use cortisone acetate in Addison's disesase, where the treatment had to be supplemented with sodium chloride or deoxycortone acetate to achieve a satisfactory electrolyte balance (59). In November 1950, Merck made cortisone available to physicians in the US (60). Since then patients with adrenal insufficiency have been treated with glucocorticoid, and since the introduction of fludrocortisone in the 1950s, replacement therapy has remained virtually unchanged (10).…”

Section: Evolution Of Glucocorticoid Replacement Therapymentioning

confidence: 99%

Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy

Debono

Ross²,

Newell‐Price

2009

European Journal of Endocrinology

113

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Patients with adrenal insufficiency need lifelong glucocorticoid replacement, but many suffer from poor quality of life, and overall there is increased mortality. Moreover, it appears that use of glucocorticoids at the higher end of the replacement dose range is associated with increased risk for cardiovascular and metabolic bone disease. These data highlight some of the inadequacies of current regimes.The cortisol production rate is estimated to be equivalent to 5.7-7.4 mg/m 2 per day, and a major difficulty for replacement regimes is the inability to match the distinct circadian rhythm of circulating cortisol levels, which are low at the time of sleep onset, rise between 0200 and 0400 h, peaking just after waking and then fall during the day. Another issue is that current dose equivalents of glucocorticoids used for replacement are based on anti-inflammatory potency, and few data exist as to doses needed for equivalent cardiovascular and bone effects. Weight-adjusted, thrice-daily dosing using hydrocortisone (HC) reduces glucocorticoid overexposure and represents the most refined regime for current oral therapy, but does not replicate the normal cortisol rhythm. Recently, proof-of-concept studies have shown that more physiological circadian glucocorticoid therapy using HC infusions and newly developed oral formulations of HC have the potential for better biochemical control in patients with adrenal insufficiency. Whether such physiological replacement will have an impact on the complications seen in patients with adrenal insufficiency will need to be analysed in future clinical trials.

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Section: Evolution Of Glucocorticoid Replacement Therapymentioning

confidence: 99%

Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy

Debono

Ross²,

Newell‐Price

2009

European Journal of Endocrinology

113

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“…Nevertheless, this observation confirmed the principle value of the screen and provoked even more interest and greater efforts. As a next step, Ehrlich started to examine organic arsenic derivatives [32,33,34,35]. In 1905, his coworker Alfred Bertheim (1879-1914) deciphered the chemical structure of Atoxyl as an amino derivative of phenyl arsenic acid.…”

Section: From Drug Screening To the Development Of Targeted Drugsmentioning

confidence: 99%

“…This knowledge opened the door for modifying drug properties by artificially changing its chemical structure. Subsequently, a number of derivatives were synthesized with the aim of enhancing their therapeutic efficacy and of lowering their toxicity [9,32,33,34]. Finally, by adding substitutes to the amino group of Atoxyl, compound No.…”

Section: From Drug Screening To the Development Of Targeted Drugsmentioning

confidence: 99%

Paul Ehrlich (1854-1915) and His Contributions to the Foundation and Birth of Translational Medicine

Valent

Groner²,

Schumacher³

et al. 2016

J Innate Immun

273

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Translational research and precision medicine are based on a profound knowledge of cellular and molecular mechanisms contributing to various physiologic processes and pathologic reactions in diverse organs. Whereas specific molecular interactions and mechanisms have been identified during the past 5 decades, the underlying principles were defined much earlier and originate from to the seminal observations made by outstanding researchers between 1850 and 1915. One of the most outstanding exponents of these scientists is Paul Ehrlich. His work resulted not only in the foundation and birth of modern hematology and immunology, but also led to the development of chemotherapy and specific targeted treatment concepts. In 2015, the Medical University of Vienna organized a memorial meeting, with the aim of honoring Paul Ehrlich's contributions to science, and to commemorate the 100th anniversary of his death. The authors of the current review served as faculty members and dedicate this paper to Paul Ehrlich and his remarkable contributions to medicine.

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“…Together with the contributions of his disciple Oswald Schmiedeberg , these achievements formed the basis for advances in pharmacological research [2] .…”

mentioning

confidence: 99%

“…In order to obtain safer drugs, the structure of toxic drugs was modified or new chemical compounds were synthesized. This systematic approach was of key importance in obtaining drugs that were introduced in the early twentieth century [2] .…”

mentioning

confidence: 99%

The Contributions of Paul Ehrlich to Pharmacology: A Tribute on the Occasion of the Centenary of His Nobel Prize

2008

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On the centenary of Paul Ehrlich’s Nobel Prize, this German researcher deserves to be remembered as a pioneer in a large number of scientific disciplines. As a result of his enthusiasm and scientific abilities, dedication, and contacts with other scientists of his time, he was able to make countless contributions in fields as diverse as histology, haematology, immunology, oncology, microbiology and pharmacology, among others. Although the Swedish award was meant to recognize the standardization of the manufacture of antidiphtheria serum, it was the discovery of arsphenamine (Salvarsan) for the treatment of syphilis which won him wider international acclaim. From a pharmacological perspective, Ehrlich’s outstanding contributions include dissemination of the ‘magic bullet’ concept for the synthesis of antibacterials, introduction of concepts such as chemoreceptor and chemotherapy, and linking the chemical structure of compounds to their pharmacological activity. These achievements took place within the framework he established for the transition from experimental pharmacology to therapeutic pharmacology. He introduced a modern research system based on the synthesis of multiple chemical structures for pharmacological screening in animal models of disease states. These contributions were undoubtedly decisive in propitiating the wider development of antibiotics decades later. For these reasons, it is fitting to mark the 100th anniversary of the Nobel Prize awarded to this great scientist by commemorating the importance of his contributions to the advance of pharmacology.

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A Brief History of Great Discoveries in Pharmacology: In Celebration of the Centennial Anniversary of the Founding of the American Society of Pharmacology and Experimental Therapeutics

Cited by 75 publications

References 179 publications

Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy

Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy

Paul Ehrlich (1854-1915) and His Contributions to the Foundation and Birth of Translational Medicine

The Contributions of Paul Ehrlich to Pharmacology: A Tribute on the Occasion of the Centenary of His Nobel Prize

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