History of Medicinal Practices

Early Medicinal Practices

• Ancient civilizations (Chinese, Hindus, Mayans, Mediterranean) used therapeutic plants and minerals.
• Emperor Shen Nung's pharmacopeia included antimalarial ch'ang shang and ephedrine-containing ma huang.
• Indigenous American Indians used chaulmoogra fruit.
• Pecacuanha root, containing emetine, treated dysentery and amebiasis in Brazil.
• South American Indians used coca leaves (cocaine) and mushrooms (methylated tryptamine) as hallucinogens.
• Early Greek apothecary shops offered opium, squill, Hyoscyamus, viper toxin, and metallic drugs like copper, zinc, iron sulfate, and cadmium oxide.

Medieval Period (13th-16th Centuries)

• Advancement in chemistry and physics moved from Greco-Roman to Arabian alchemists.
• Paracelsus emphasized antimony and its salts as cures-alls, based on the belief that chemicals could cure disease.

19th Century Medicinal Chemistry

• Increased understanding of chemistry expanded herbal pharmacopeia.
• Antoine Lavoisier and other chemists refined chemical analysis techniques.
• Adolph Kolbe's synthesis of acetic acid in 1845 and Pierre Berthelot's synthesis of methane in 1856 advanced organic chemistry.
• Pharmacognosy gave way to physiologic chemistry, focusing on active ingredients rather than the crude plant material.
• Friedrich Sertürner isolated morphine in 1803.
• Pierre-Joseph Pelletier isolated and purified caffeine, quinine, and colchicine in 1820, as well as emetine in 1816.
• William Withering found a treatment for edema.
• Albert Niemann isolated cocaine in 1860 and physostigmine in 1864.
• Pharmaceutical industry emerged at the end of the century due to the above discoveries.

20th Century and Pharmaceutical Industry

• Synthetic chemotherapeutic agents emerged to combat protozoal and spirochetal diseases.
• Prontosil (2,4-diaminoazobenzene4′-sulfonamide) cured dangerous bacterial infections.
• Discovery that bacteriostatic action of sulfonamides is antagonized by p-aminobenzoic acid exemplified structural analogies' role.
• Alexander Fleming's discovery of penicillin in 1929, further examined by Florey and Chain in 1941, provided a highly potent antibacterial agent.
• Advancements in antibiotics led to significant changes in medical practice.

Psychopharmacological Agents

• Long history of using CNS-active agents in psychiatry.
• Stimulants and depressants were used to modify mood and state.
• Chlorpromazine's synthesis (1950) revolutionized schizophrenia treatment. Debate on discovery, no Nobel Prize was awarded.
• Iproniazid's antidepressant effects, leading to MAO inhibitors (phenelzine, tranylcypromine).
• Development of tricyclic antidepressants, structural analogs of phenothiazines (imipramine).
• Selective serotonin reuptake inhibitors (SSRIs) emerged from the early work on R,S-zimelidine to R,S-fluoxetine (Prozac).
• Antianxiety agents, including benzodiazepines (e.g., chlordiazepoxide, diazepam), were discovered through random screening.

Endocrine Therapy and Steroids

• Epinephrine, the first pure hormone isolated from an endocrine gland, led to developments in sympathomimetic amines.
• Isolation and characterization of various hormones from glands.
• Edward Kendall isolated thyroxine and established cortisone activity.
• Discovery of insulin in 1921 by Banting and Best, purified and produced commercially by 1922.
• Genetic engineering allowed for the development of genetically engineered human insulin in the 1970s, such as Humulin.
• Development of inhaled insulin in 2006.
• Isolation and purification of several peptide hormones allowed for synthetic peptide production.
• Extensive advancement in steroid hormones, including birth control steroids using naturally occurring substances.
• Carl Djerassi synthesized norethindrone, a first orally active contraceptive.
• Synthesis and clinical use of progesterone and norethindrone for oral contraceptive.
• The pill revolutionized women's economic and social structure.
• Discovery of glucocorticoids and synthesis of the abortion pill (mifepristone).

Anesthetics and Analgesics

• Introduction of nitrous oxide, ether, and chloroform as anesthetics in the 1840s.
• Paracelsus popularized opium use in Europe (laudanum method of administration).
• Frederick Sertürner isolated morphine in 1805.
• Morphine and other opium alkaloids inspired synthetic analgesics (heroin, oxycodone).
• Methadone as a heroin/morphine maintenance treatment. Opiate addiction is a medical condition.
• Proposed that opiate effects were receptor-mediated, which was later demonstrated.
• Characterization of opioid receptors and radioreceptor binding assays.

Hypnotics and Anticonvulsants

• Alcoholic beverages and opium potions for sleep induction.
• Bromides, chloral hydrate, paraldehyde, urethane, and sulfenal as sedative-hypnotics.
• Synthesis of diethyl acetyl urea and 5,5-diethylbarbituric acid as hypnotics.
• Phenobarbital as a hypnotic and anticonvulsant, leading to hydantoins.
• Phenytoin (Dilantin) as a major anticonvulsant.

Local Anesthetics

• Cocaine, isolated from coca, is a significant natural local anesthetic.
• Koller's discovery of cocaine's eye anesthetic properties.
• Structural modifications of cocaine led to important local anesthetics (benzocaine, procaine, tetracaine, lidocaine)

Drugs Affecting Renal and Cardiovascular Function

• Digoxin (widely used cardiac glycoside) for myocardial ischemia, heart failure, and arrhythmias.
• William Withering discovered the benefit of foxglove (Digitalis purpurea) for fluid buildup.
• Purification and structure determination of digitoxin and other digitalis glycosides
• Development of cholesterol-lowering statins (compactin/mevastatin), leading to lovastatin and Pravachol.
• Michael Brown and Joseph Goldstein's Nobel Prize-winning work in cholesterol metabolism.

Anticancer Agents

• Sulfur mustard gas's use and its antitumor properties.
• 6-Mercaptopurine as an effective leukemia drug with a focus on nucleic acid interference to block tumor growth similar to sulfonamides.
• Cisplatin’s use against many cancers (testicular, ovarian, bladder, lung, and stomach).
• Discovery of Paclitaxel (Taxol) from yew tree bark that stabilizes cell structures, inhibiting division and multiplication.

Old Drugs as Targets for New Drugs

• Natural sources are still useful (e.g. Cannabis).
• Isolation and determination of tetrahydrocannabinol (THC) structure, leading to endocannabinoid receptor research and new cannabis-inspired drug classes.

Molecular Imaging

• Application of radiopharmaceuticals and contrast agents for non-invasive imaging (scintigraphy, radiography, ultrasonography, PET, SPECT, MRI).
• Use of cyclotrons and nuclear reactors as tools to develop new radiotracers.
• Methods for monitoring drug response in therapy effectiveness.

The Next Wave in Drug Discovery (Genomics)

• Imatinib (Gleevec) discovered through high throughput screening and medicinal chemistry, treating chronic myeloid leukemia.
• Emphasis on understanding patient genes for more effective therapies.
• Drug formulations focused on reaching specific targets.
• Vaccine development using proprietary plasmid DNA.

Combinatorial Chemistry and High-Throughput Screening

• Combinatorial chemistry and high-throughput screening methods reduce drug development time and cost.
• Automated and miniaturized synthesis of large drug libraries to efficiently screen for novel compounds.
• Systematic and repetitive creation of diverse molecules.
• Combining new technology with traditional methods.