Department of Pharmacology decade by decade

1940s

• Department of Pharmacology founded with William Salter as the first chair.

• Discovery of first anticancer agent, nitrogen mustard, for treatment of lymphoma; demonstration of its effectiveness and the development of drug resistance by Alfred Gilman, Louis Goodman and Gustaf Lindskog.

1950s

• Discovery of first antiviral agent, IUdR, for the treatment of ocular herpes, a major cause of blindness, by William Prusoff.

• Arnold Welch becomes chair and develops first biochemically oriented pharmacology department in the country, steering the field away from a physiological approach.

1960s

• Work by Joseph Bertino on mechanism of action of antifolate chemotherapeutic agents which contributed to use of methotrexate, an anticancer agent still in wide use.

• Floyd Bloom and George Aghajanian pioneer electron-microscopic studies of the monoamine neurons in the central nervous system which underlie anxiety, depression and other psychiatric disorders.

• Nicholas Giarman and Daniel Freedman show that LSD alters the function of serotonin neurons, providing a connection between this neurotransmitter and psychosis.

• Robert Roth and Giarman discover that the central nervous system depressant gamma hydroxybutyrate is a naturally occurring endogenous brain metabolite that influences the function of dopamine neurons.

• Murdoch Ritchie recruited as chair, bringing with him two full professors, Paul Greengard and William Douglas.

1970s

• Alan Sartorelli elucidates the concept of bioreductive activation of prodrugs by oxygen-deficient (hypoxic) tumor cells.

• Sartorelli and Sara Rockwell demonstrate preferential kill of hypoxic tumor cells by mitomycin C, leading to clinical use of drug with ionizing irradiation in treatment of cancers of the head and neck.

• Ritchie provides seminal contributions to the understanding of the mechanism of action of local anesthetics.

• Greengard describes the function of the cyclic nucleotides, molecules regulating metabolism, which ultimately leads to his being awarded a Nobel Prize in Physiology or Medicine.

• Discovery and characterization of dopamine autoreceptors by Aghajanian, Benjamin Bunney and Roth lead to the development of dopamine autoreceptor-selective drugs for the treatment of psychiatric disorders.

• Douglas conducts pioneering work on the essential role of calcium in “stimulus-secretion coupling” in the release of hormones and neuromodulators.

1980s

• Discovery of Zerit (d4T) for the treatment of AIDS by Prusoff and Tai-Shun Lin.

• Aghajanian and Herbert Kleber show clonidine, an antihypertensive drug, is useful in treating opiate withdrawal.

• Discovery of cyclophilin, the receptor for the important immunosuppressive agent cyclosporine, by Robert Handschumacher.

• Studies by Roth on MPTP in monkeys lead to a primate model of Parkinson’s disease and the development of neural grafts, gene therapy and stem cells for treatment of this disease.

1990s

• Sartorelli’s laboratory discovers two anticancer compounds, Triapine and VNP40101M, currently in clinical trials.
Yung-Chi Cheng discovers one anticancer and five antiviral agents, currently in clinical trials.

• Robert Innis develops transmitter-specific SPECT and PET imaging probes to study integrity of brain dopamine systems in the central nervous systems of humans and monkeys.
Leonard Kaczmarek’s pioneering work on potassium channels reveals how a certain type of potassium channel underlies the fidelity of firing of auditory neurons.

• Bunney shows that dopamine cell depolarization blockade is a useful model for predicting the therapeutic efficacy of antipsychotic drugs.

• Eric Nestler conducts studies of molecular mechanism of drug addiction and dependence, identifying delta FosB as a molecular switch for addiction.

• Ronald Duman’s studies on synaptic plasticity and mood disorders provide insight for development of novel therapeutics. Roth develops primate model of cortical dopamine deficiency and enduring cognitive dysfunction useful in study of drugs for cognitive disorders.

• James Howe describes fundamental properties of single glutamate-gated ion channels (which underlie most excitatory transmission in the brain).

2000s

• Joseph Schlessinger becomes department chair and oversees significant expansion.

• Tamas Horvath and Roth demonstrate that coenzyme Q is neuroprotective in the monkey MPTP model of Parkinson’s disease.

• Marina Picciotto’s work using genetically altered mice helps in understanding the basis of nicotine addiction.

Sources: Robert Roth, Alan Sartorelli and William Sessa