List of drugs by year of discovery

See also: List of drugs

The following is a table of drugs organized by their year of discovery.

Naturally occurring chemicals in plants, including alkaloids, have been used since pre-history. In the modern era, plant-based drugs have been isolated, purified and synthesised anew. Synthesis of drugs has led to novel drugs, including those that have not existed before in nature, particularly drugs based on known drugs which have been modified by chemical or biological processes.

Antiquity

Prehistory

Archaeological evidence indicates that the use of medicinal plants dates back to the Paleolithic age.[citation needed]

4th millennium BCE

In ancient Egypt, herbs are mentioned in Egyptian medical papyri, depicted in tomb illustrations, or on rare occasions found in medical jars containing trace amounts of herbs.[1] Medical recipes from 4000 BCE were for liquid preparations rather than solids.[2] In the 4th millennium BCE, Soma (drink) and Haoma are named, but is not clear what ingredients were used to prepare them.[citation needed]

3rd millennium BCE

Discovery Name of drug Active ingredients
2,700 BCE Cannabis sativa Cannabinoids, (e.g. tetrahydrocannabinol, a cannabinoid agonist, and cannabidiol, an analgesic and anticonvulsant).[3]
2,700 BCE Mandragora officinarum Atropine and scopolamine (antimuscarinics), scopine, cuscohygrine, apoatropine, Belladonnines and non-alkaloid constituents including sitosterol and scopoletin.[citation needed]
2,700 BCE Rhubarb Anthraquinones, (e.g. emodin)[4] which are cathartic and laxative. Stilbenoids (e.g. rhaponticin), which may lower blood glucose levels.[5] Flavanol glucosides (e.g. (−)-catechin-7-O-glucoside) which may be cytoprotective.[6]

2nd millennium BCE

Written around 1600 BCE, the Edwin Smith Papyrus describes the use of many herbal drugs. The Ebers Papyrus – one of the most important medical papyri of ancient Egypt – was written around 1550 BCE, and covers more than 700 drugs, mainly of plant origin.[7] The first references to pills were found on papyri in ancient Egypt, and contained bread dough, honey, or grease. Medicinal ingredients such as plant powders or spices were mixed in and formed by hand to make little balls, or pills.[2] The papyri also describe how to prepare herbal teas, poultices, ointments, eye drops, suppositories, enemas, laxatives, etc. Aloe vera was used in the 2nd millennium BCE.[8]

1st millennium BCE

In Greece, Theophrastus of Eresos wrote Historia Plantarum in the 4th century BCE.[9] Seeds likely used for herbalism have been found in archaeological sites of Bronze Age China dating from the Shang dynasty[10] (c. 1600 BCE–c. 1046 BCE). Over a hundred of the 224 drugs mentioned in the Huangdi Neijing – an early Chinese medical text – are herbs.[11] Herbs also commonly featured in the medicine of ancient India, where the principal treatment for diseases was diet.[12]

A sample of raw opium

Opioids are among the world's oldest known drugs.[13][14] Use of the opium poppy for medical, recreational, and religious purposes can be traced to the 4th century BCE, when Hippocrates wrote about it for its analgesic properties, stating, "Divinum opus est sedare dolores." ("Divine work is the easing of pain")[15]

Year of discovery Name of the drug Active ingredients
1st millennium BC Hyoscyamus niger Tropane alkaloids (e.g. hyoscyamine and scopolamine).[16]
600 B.C. Glycerol, produced Glycerol[citation needed]
300 B.C. Opium Phenanthrenes (e.g. morphine, codeine, and thebaine).[17] Morphine binds to and activates Mu opioid receptors and is analgesic. Opium also contains isoquinolines (e.g. papaverine and noscapine).

1st century CE

In ancient Greece, pills were known as katapotia ("something to be swallowed"). Pliny the Elder, who lived from 23–79 CE, first gave a name to what we now call pills, calling them pilula.[2] Pliny also wrote Naturalis Historia a collection of 38 books and the first pharmacopoea.

Pedanius Dioscorides wrote De Materia Medica (c. 40 – 90 CE); this book dominated the area of drug knowledge for some 1500 years until the 1600s.[18]

Jojoba was used in the 1st millennium CE.

2nd century CE

Aelius Galenus wrote more than 11 books about drugs, also use terra sigillata with kaolinite and goats blood to produce tablets.

Post-classical to Early modern

Drugs developed in the post-classical (circa 500 to 1450) or early modern eras (circa 1453 to 1789).

6th–11th century CE

In middle age ointments were a common dosage form.

Year of discovery Name of the drug Active ingredients
10th century Coffee Caffeine (adenosine receptor antagonist)[citation needed]

Beta carboline (GABAA receptor inverse agonist)[citation needed]

11th century CE

Avicenna separates Medicine and Pharmacy, in 1025 published his book The Canon of Medicine, an encyclopedia of medicine formed by five books. Drugs mentioned by Avicenna include agaric, scammony and euphorbium.[19] The latex of Euphorbia resinifera contains resiniferatoxin, an ultra potent capsaicin analog. Desensitization to resiniferatoxin is tested in clinical trials to treat neuropathic pain.[20]

Year of discovery Name of the drug Active ingredients
Before 1025 Agaric Muscimol (GABAA receptor agonist), muscarine (muscarinic receptor agonist), and ibotenic acid (NMDA receptor agonist)[citation needed]
Before 1025 Scammony Scammonin

(In general, a powerful purgative and anthelmintic)[citation needed]

Before 1025 Euphorbium Resiniferatoxin (capsaicin analog and possible analgesic)[citation needed]

16th century CE

Paracelsus expounded the concept of dose response in his Third Defense, where he stated that "Solely the dose determines that a thing is not a poison." This was used to defend his use of inorganic substances in medicine as outsiders frequently criticized Paracelsus' chemical agents as too toxic to be used as therapeutic agents. Paracelsus discovered that the alkaloids in opium are far more soluble in alcohol than water. Having experimented with various opium concoctions, Paracelsus came across a specific tincture of opium that was of considerable use in reducing pain. He called this preparation laudanum.[citation needed]

For over a thousand years South American indigenous peoples have chewed Erythroxylon coca leaves, which contain alkaloids such as cocaine. Coca leaf remains have been found with ancient Peruvian mummies.[21] There is also evidence coca leaves were used as an anesthetic.[22] In 1569, Spanish botanist Nicolás Monardes described the indigenous peoples' practice of chewing a mixture of tobacco and coca leaves to induce "great contentment".[citation needed]

1400s Nicotine (Tobacco)[citation needed]

Year of discovery Name of the drug
Before 1569 Erythroxylon coca leaves (containing cocaine)[citation needed]
16th century Laudanum[citation needed]

18th century CE

In 1778 John Mudge created the first inhaler devices.[citation needed] In 1747, James Lind, surgeon of HMS Salisbury, conducted the first clinical trial ever recorded, on it he studied how citrus fruit were capable of curing scurvy.[citation needed]

Modern

19th century CE

In the 1830s chemist Justus von Liebig began the synthesis of organic molecules, stating that "The production of all organic substances no longer belongs just to living organisms." In 1832 produced chloral hydrate, the first synthetic sleeping drug. In 1833 French chemist Anselme Payen was the first to discover an enzyme, diastase. In 1834, François Mothes and Joseph Dublanc created a method to produce a single-piece gelatin capsule that was sealed with a drop of gelatin solution. In 1853 Alexander Wood was the first physician that used hypodermic needle to dispense drugs via Injections. In 1858 Dr. M. Sales Giron invented the first pressurized inhaler.

Amphetamine was first synthesized in 1887 in Germany by Romanian chemist Lazăr Edeleanu who named it phenylisopropylamine;[23][24][25] its stimulant effects remained unknown until 1927, when it was independently resynthesized by Gordon Alles and reported to have sympathomimetic properties.[25] Shortly after amphetamine, methamphetamine was synthesized from ephedrine in 1893 by Japanese chemist Nagai Nagayoshi.[26] Three decades later, in 1919, methamphetamine hydrochloride was synthesized by pharmacologist Akira Ogata via reduction of ephedrine using red phosphorus and iodine.[27]

Year of discovery Name of the drug Synthesis mechanism Year that was Patented Governmental approval Patented expired
Synthesis discoverer Year
1803–1805[28] Morphine Gates synthesis[29] 1952
1820 Quinine (isolation) Woodward and Doering 1944
1830s Santonin
1832 Chloral hydrate Justus von Liebig 1832
1833 Diastase
1853 Acetylsalicylic acid (Aspirin) 1899
1875 Phenylhydrazine Hermann Emil Fischer 1875 1875
1877 Paracetamol Harmon Northrop Morse 1877 1950 2007
1877 Mannitol Julije Domac 1877 1950
1880 Phenazone, "the mother of modern Antipyretics" Ludwig Knorr 1880 1880
1885 Ephedrine Nagai Nagayoshi 1885 1885
1890 Benzocaine August Bischler 1895 1895
1895 Quinazoline August Bischler 1895 1895
1887 Amphetamine Lazăr Edeleanu 1887
1893 Methamphetamine Nagai Nagayoshi 1893

20th century CE

In 1901 Jōkichi Takamine isolated and synthesized the first hormone, Adrenaline. In 1907 Alfred Bertheim synthesized Arsphenamine, the first man-made antibiotic. In 1927 Erik Rotheim patented the first aerosol spray can. In 1933 Robert Pauli Scherer created a method to develop softgels.

William Roberts studies about penicillin were continued by Alexander Fleming, who in 1928 concluded that penicillin had an antibiotic effect. In 1944 Howard Florey and Ernst Boris Chain mass-produced penicillin. In 1948 Raymond P. Ahlquist published his seminal work where he divided adrenoceptors into α- and β-adrenoceptor subtypes, this allowed a better understanding of drugs mechanisms of action.

In 1987, after Montreal Protocol, CFC inhalers were phased out and HFA inhalers replace them. In 1987 CRISPR technique was discovered by Yoshizumi Ishino that in the next century would be used for genome editing.

Year of discovery Name of the drug Year when the synthesis mechanism was developed Year that was Patented Governmental approval Patented expired
1901 Adrenaline Jōkichi Takamine, 1901 1901 1901 N/A (Natural Hormone)
1906 Oxytocin Discovered by Henry Hallett Dale, synthesized by Vincent du Vigneaud in 1952 1925 1926 N/A (Natural Hormone)
1907 Arsphenamine Alfred Bertheim, 1907 N/A N/A N/A
1908 Phenytoin Heinrich Biltz, 1908 N/A N/A N/A
1912 Vitamin C Tadeusz Reichstein, 1933 N/A N/A N/A
1912 Phenobarbital Fischer and Mering Synthesis, 1912 1912 1912 1932
1915 Thyroxine Isolated by Edward Calvin Kendall, 1915 1915 1915 N/A (Natural Hormone)
1918 Ergotamine Isolated by Arthur Stoll, Sandoz, 1918 1918 1918 1938
1920 Metamizole 1920 N/A N/A N/A
1921 Insulin Frederick Grant Banting, 1921 1921 1921 N/A (Natural Hormone)
1927 Levothyroxine Harington and Barger Synthesis, 1927 N/A 1927 (Synthetic hormone)
1928 Penicillin Alexander Fleming, 1928 1928 1928 Never patented
1932 Sulfanilamide Paul Josef Jakob Gelmo, 1908 N/A N/A 1938
1932 Prontosil Gerhard Domagk, Josef Klarer and Fritz Mietzsch 1932 N/A N/A 1938
1935 Cortisone Isolated by Philip Showalter Hench and Edward Calvin Kendall, 1935 1935 1935 N/A (Natural Hormone)
1935 Tetracaine 1935 1935 1935 1955
1935 Methylphenobarbital 1935 1935 1935 1955
1935 Dapsone 1935 1935 1935 1955
1940 Dicoumarol (warfarin) 1940, extracted from Melilotus 1940 1940 1960
1946 Isosorbide 1946 1946 1946 1966
1943 Lidocaine Nils Löfgren, 1943 1946 1949 1966
1938 Lysergic acid diethylamide (LSD) Albert Hofmann, Sandoz 1938 1938 1958
1951 Hydrocortisone 1951 1951 1951 1971
1951 Imipramine 1951 1951 1957 1971
1952 Acetazolamide 1952 1952 1952 1972
1954 Fludrocortisone acetate 1954 1954 1954 1974
1955 Prednisolone 1955 1955 1955 1975
1955 Prednisone 1955 1955 1955 1975
1955 Chlordiazepoxide Leo Sternbach, Hoffmann-La Roche, 1955 1955 1955 1975
1956 Methylprednisolone 1956 1956 1956 1976
1956 Triamcinolone 1956 1956 1956 1976
1957 Spironolactone 1957 1957 1957 1977
1957 Mepivacaine A. F. Ekenstam, 1957 1957 1957 1977
1957 Bupivacaine 1957 1957 1957 1977
1957 Chlorothiazide 1957 1957 1957 1977
1958 Dexamethasone 1958 1958 1958 1978
1958 Betamethasone 1958 1958 1958 1978
1958 Clozapine 1958 1958 1958 1978
1958 Triamcinolone acetonide (Nasacort) 1958 1958 1958 1978
1959 Hydrochlorothiazide 1959 1959 1959 1979
1959 Chlortalidone 1959 1959 1959 1979
1960 Fentanyl Paul Janssen, Janssen Pharmaceutica 1960 1960 1969 1980
1961 Mefenamic acid Claude Winde, Parke-Davis 1961 1961 1969 1981
1961 Ibuprofen Boots Group, 1961 1961 1969 1981
1961 Flurbiprofen Boots Group, 1961 1961 1969 1994
1962 Trimethoprim 1962 1982
1962 Furosemide Calvin L. Stevens, Parke-Davis 1962 1962 1982
1962 Ketamine Calvin L. Stevens, Parke-Davis 1962 1962 1982
1962 Piroxicam Pfizer 1962 1962 1992
1962 Meloxicam Pfizer 1962 1962 Not for use in humans
1962 Beclometasone David Jack, 1962 1962 1982
1963 Diazepam Leo Sternbach, 1963 1963 1963 1983
1963 Indometacin 1963 1963 1965 1983
1963 Flufenamic acid Parke-Davis, 1963 1963 1965 1983
1963 Ropivacaine 1963 1963 1963 1983
1964 Meclofenamic acid Parke-Davis, 1963 1963 1965 1983
1964 Propranolol James Black, 1964 1964
1964 Clonazepam Leo Sternbach, 1964 1964 1964 1984
1964 Triamterene 1964 1964 1964 1984
1964 Tetrahydrocannabinol (dronabinol) 1964 1964 1964 N/A
1966 Salbutamol (Albuterol) David Jack, Allen & Hanburys, 1966 1966 1986
1967 Amiloride 1964 1964 1964 1984
1968 Prilocaine 1968 1968 1968 N/A
1970 Ciclosporin B. Vithal Shetty, 1971 1982
1971 Metolazone B. Vithal Shetty, 1971 1971
1971 Cimetidine James Black, 1971 1971
1971 Mupirocin Isolated in 1971 1971
1971 Etidocaine Isolated in 1971 1971
1973 Diclofenac Synthesized by Alfred Sallmann and Rudolf Pfister in 1973 1973 1993
1973 Budesonide 1973 1973 1993
1974 Sufentanil Janssen Pharmaceutica, 1974 1994
1974 Carfentanil Janssen Pharmaceutica, 1974 1994
1976 Ipratropium bromide 1976 1976 1996
1976 Naproxen 1976 1976 1996
1977 Ranitidine John Bradshaw, Allen & Hanburys, 1977 1981
1977 Propofol John Bradshaw, Allen & Hanburys, 1977 1981
1977 Tramadol Grünenthal GmbH, 1977 1977 1997
1981 Verapamil 1981 1981 1997
1985 Salmeterol (Serevent) David Jack, Allen & Hanburys, 1985 1985 2005
1984 Sumatriptan David Jack, 1984 1984 2006
1987 Ondansetron David Jack, 1987 1990 2006
1989 Ketorolac 1989 1989 2009
1993 Fluticasone propionate David Jack, 1993 1993 2004
1993 Ketoprofen James W. Young, William J. Wechter and Nancy M. Gray in 1993 1993 2003
1993 Celecoxib 1993 1993 2003
1993 Rofecoxib 1993 1993 2003
1995 Parecoxib 1995 Not approved 2015
1996 Lopinavir 2000 -
1997 Mometasone furoate (Nasonex) 1997 1997 2017
1997 Eletriptan 1997 2002 2017
1998 Ropivacaine 1998 1998 1998 2008
1998 Leflunomide 1998 1998 2008

21st century CE

21st century begins with the first complete sequences of individual human genomes by Human Genome Project, on 12 February 2001, this allowed a switch in drug development and research from the traditional way of drug discovery that was isolating molecules from plants or animals or create new molecules and see if they could be useful in treatment of illness in humans, to pharmacogenomics, that is the study and knowledge of how genes respond to drugs. Another field beneficed by Human Genome Project is pharmacogenetics, that is the study of inherited genetic differences in drug metabolic pathways which can affect individual responses to drugs, both in terms of therapeutic effect as well as adverse effects.[30]

Humane genome study also allowed to identify which genes are responsible of illness, and to develop drugs for rare diseases and also treatment of illness through gene therapy. In 2015 a simplified form of CRISPR edition was used in humans with Cas9, and also was used an even more simple method, Cas12a that prevent genetic damage from viruses. These advances are improving personalized medicine and allowing precision medicine.

Year of discovery Name of the drug Year when the synthesis mechanism was developed Year that was Patented Governmental approval Patented expiry Drug type *
2000 Bevacizumab 2004 2024 MA
2001 Valdecoxib 2016 N/A SM
2001 Etoricoxib 2016 N/A SM
2003 Alirocumab 2015 2035 MA
2006 Linagliptin 2011[31] 2031 SM
2007 Apixaban 2012 2032 SM
2007 Alectinib 2014 2014 SM
2007 Sofosbuvir 2007, Raymond F. Schinazi.[32][33] N/A N/A N/A SM
2007 Bevirimat SM
2012 Ivacaftor 2012 2032 SM
2013 Vilanterol 2013 2033 SM
2014 Evolocumab 2015 2035 MA
2014 Umeclidinium bromide (Incruese Ellipta) 2014 2034 SM
2014 Tisagenlecleucel 2017 2037 ACT

* MA = Monoclonal antibody

SM = Small molecule

ACT = Adoptive cell transfer

See also

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