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Tuesday, 28.03.2017

Resume - Leonard Cook, PhD

Dr. Leonard Cook attended Rutgers University for a B.A. and Yale University School of Medicine, Dept. of Pharmacology for a Ph.D. in pharmacology. While at Yale his research project involved the study of the spinal and central effects of narcotic analgesics.

He subsequently joined Smith Kline & French Laboratories and had a dominant role in the development of their Department of Pharmacology. At SK&F Labs he initiated a research project designed to identify agents which selectively inhibit gastric secretion. He also initiated a non-barbiturate sedative program. An unexpected discovery in the sedative research was a drug potentiator (enzyme inhibitor, SKF 525A), which had a significant impact on the development of the field of drug metabolism. An important input in the ensuing research was a sample of R.P. 4560 (chlorpromazine) that he acquired from Rhone-Poulenc-Paris for comparison, which was reported at that time to be simply another drug potentiator. His work clearly demonstrated that chlorpromazine was primarily a unique CNS agent, especially on the basis of its effects in his newly developed test procedures in the non-barbiturate sedative program.

The data on the behavioral pharmacological actions of chlorpromazine supported the unusual anecdotal reports then coming from France regarding its therapeutic effects in psychotic patients. The extensive pharmacology he carried out with these new psychopharmacological tests prompted a meeting of the Rhone-Poulenc scientists and their management with himself and SKF management. This led to the fruitful collaboration agreement and the development of chlorpromazine (Thorazine) for the U.S. market.

Dr. Cook directed the evaluation of the full pharmacological profile of Thorazine, elaborating its antiemetic, psychotherapeutic and hypothermic properties. He participated in the setting up of early clinical trials to establish the utility of these properties, e.g., hypothermia for cardiac surgery, and the therapeutic effect in psychiatric disorders. He directed the development of an extensive and sophisticated research program in psychopharmacology which was acknowledged internationally. Among compounds developed were Compazine, Stelazine, Parnate, the antiemetic Vontrol, as well as several other agents which underwent various degrees of development. Many of the laboratory test procedures he developed became standard approaches used internationally. This work had a significant impact on the strategy of research in psychopharmacology carried out in many academic and industrial laboratories.

His original work in antipsychotic research led him to expand into other facets of CNS pharmacology such as antidepressants (Parnate, MAO inhibitor), antianxiety agents and research designed to identify agents useful in senility and mental retardation. This latter area now is defined as drugs to enhance cognition and mental performance. Research efforts in the CNS area also included analgetic compounds and elucidation of their antinociceptive and behavioral properties. These research activities represented a broad approach which included behavioral, neurobiochemical and neurophysiological techniques.

His role at SK&F Labs included an active participation in the Drug Licensing efforts. He helped to establish criteria to select agents for further consideration, and defined the equally important issue of how much internal laboratory evaluation effort could be spent on such acquisition products without unduly affecting evaluation of internally generated compounds.

He was given broader departmental responsibilities as Associate Director of Pharmacology (about 80-100 people) and was responsible for analgetic, cardiovascular, antitussive, anti-inflammatory, bronchopulmonary, gastrointestinal pharmacology, in addition to the psychotherapeutic area.

In 1969, Dr. J. J. Burns of Hoffmann-La Roche offered him a position at Roche with the objective of assuming Directorship of Pharmacology upon retirement of Dr. L. O. Randall. Dr. Cook joined Roche in November 1969.

He initially focussed on and shaped the cardiovascular area to include more relevant screening approaches. This involved strengthening their antihypertensive, anti-angina and antiarrthymia areas, and establishing a colony of spontaneous hypertensive rats to enhance the availability of test models for studying antihypertensive compounds.

In the CNS area he directed the setting up of animal models for measuring different types of analgetics and for identifying the primary psychotherapeutic properties of antidepressants, antipsychotics and anxiolytics. Efforts also were directed to measure side effects of these compounds such as extrapyramidal system effects (E.P.S., tardive dyskinesia), amnesia, alcohol potentiation and addiction/drug dependency liabilities. He also initiated a program designed to measure compounds useful in learning and memory deficits.

His responsibilities at Roche included supervision of up to 120 scientists, with direct line responsibility over the research efforts in biochemical pharmacology, endocrinology, cardiovascular, bronchopulmonary, analgetic, anti-inflammatory, antistress, antiparkinson and CNS/psychopharmacological groups. He was appointed Director of Pharmacology in 1975. He served on the Research Steering Committee and Drug Acquisition Committee. He was particularly involved in facilitating working relationships between biologists and medicinal chemists. This was directed towards balancing chemical activities with pharmacological capacity for compound evaluations, and establishing groups for informal joint evaluation of data and planning future efforts.

Several compounds that went into various phases of development and eventually were marketed are results of productivity under his direction (e.g. Medazolam).

In February 1983, Dr. Cook accepted an offer to join Du Pont de Nemours as Manager of Central Nervous System Diseases Research. He has restructured the CNS effort by strengthening their pharmacological capacity with new approaches and personnel and by initiating new research programs such as Cognitive Performance Enhancers and Antipsychotics. He has participated with the Director of Pharmaceutical Research in introducing several new procedures to enhance the productivity of the overall pharmaceutical research capacity and effectiveness at Du Pont.

The research activities in his group at DuPont have produced ten compounds which have been recommended and accepted for development and clinical trials. These include two cognitive enhancers, ("AVIVA" linopirdine), for memory enhancement in Alzheimer's Disease, a novel non-addictive analgesic effective in moderate to severe pain, and two novel antipsychotics. Research in his group also included isolating and identifying extracts of brain that may contain ligands for sigma receptors related to hallucinations and bizarre thoughts. His more current efforts in the area of drug abuse has identified a unique and highly effective group of compounds to treat cocaine addiction.

Dr. Cook is internationally recognized as one of the foremost pioneers in behavioral pharmacology. He has established drug behavioral interactions that are presently taught as classical principles in this field. His more recent effort in leading the research in identifying a unique cognitive enhancer and establishing its pharmacological profile represents his continued active role in drug discovery. His development of a pharmacological strategy in evaluating, in vivo, the antipsychotic properties of sigma receptor antagonists is unique and far ahead of other researchers in this field.

Dr. Cook continues to actively participate in professional affairs, having served on Council, and as Vice-President and President of different scientific societies. He continues to be active in research efforts and receives requests to speak on these findings. Among the recognitions he has received from his peers is the election to the Presidency of the American College of Neuropsychopharmacology. He has delivered a major invited address at the Presidential Symposium of this organization (December 1989) on future challenges for drug discovery and development. In addition, at this meeting he was awarded the prestigious Paul Hoch award. He serves on the Scientific Advisory Board to the FDA for establishing guidelines for Medications for Drug Abuse. He serves as a consultant to the Director of the National Institute for Drug Abuse and as a member of the PMA Commission for Medications for Drug Abuse. He was elected to the Board of Directors of the most significant scientific society in the field of drug abuse, The College on Problems of Drug Dependence. Significantly, in all of the offices and appointments described in this paragraph, he is the first and as yet the only industrial scientist to be so selected. He has three full Professorships (Adjunct appointments) in Psychiatry or Pharmacology in various Schools of Medicine in Philadelphia and honorary appointments in several Schools of Medicine in China.

Dr. Cook has received several distinguished honors: In 2004, in Paris, at the meeting of the Collegium Internationale of Neuropsychopharmacology, for the 50th anniversary of Chlorpromazine special event, he and Dr. Arvid Carlson (Nobel Laureate) were invited to present the two special lectures on their early research on chlorpromazine and their contributions to its understanding.  In April 2006, at the meeting of the American Society of Pharmacology and Experimental Therapeutics, Dr. Cook was presented with the Peter Dews Lifetime Achievement Award for his overall career contributions to the field of Behavioral Pharmacology. In July 2006, Dr. Cook was selected by the Collegium Internationale of Neuropsychopharmacology for its special Pioneers Award, to recognize his early research in this field and the special contributions to establishing the foundations in neuropsychopharmacology.

 

Leonard Cook

May 21, 2015