Preclinical research

There are multiple mechanisms known to underlie the neuronal cell damage associated with injury or disease that at least theoretically could be targeted for pharmaceutical intervention. Currently however, there is no clinically available therapeutic agent that can reliably protect the brain from progressive neurodegenerative processes for sustained periods. Due to the extensive amount of preclinical research that has been conducted in recent years, there is a basis for optimism, however, it appears likely that some of these approaches will result in clinically effective therapeutic modalities in the near future. A short overview of some of the investigational approaches to combat neurodegeneration appears below. 

Figure 11.1 shows different kinds of decisions important to preclinical research. Clearly, IT and simulation support are completely accepted at the lowest level of this diagram as ways of predicting molecular, cellular, organ, animal, or human properties, interactions, and responses (covered elsewhere in this volume). Therefore, scientists moving into leadership roles will very often be familiar with the strengths and weaknesses of such methods. 

Figure 11.1 The hierarchy of strategic and operational decisions in preclinical research.

Division of Preclinical Research National Institute on Drug Abuse Rockville, MD... 

This monograph is based upon papers and discussion from the technical review on phencyclidine which took place on May 7-9, 1985, at Rockville, Maryland. The review was sponsored by the Divisions of Preclinical Research, Clinical Research, and Epidemiology and Statistical Analysis of the National Institute on Drug Abuse. 

Doris H. Clouet, Ph.D. Neuroscience Research Branch Division of Preclinical Research... 

One of the driving forces to apply combinatorial chemistry in drug discovery is to accelerate lead discovery and preclinical research in order to find the next drug. It is important that these combinatorial library compounds are as pure as possible when performing lead discovery screening. At this stage,... 

Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd,... 

Analytical methods are important not only in the development and manufacture of commercial biopharmaceutical drugs, they also play a vital role in the whole drug development life cycle. Drug discovery and preclinical research require development and application of analytical methodologies to support identification, quantitation, and characterization of lead molecules. It is difficult to perform a comparative potency assay on lead molecules if one does not know how much of each is going into the assay or how pure the molecule is. Analytical methods are typically developed, qualified, and validated in step with the clinical... 

Drug Development Tests are performed on the lead compounds in test tubes (laboratory, in vitro) and on animals (in vivo) to check how they affect the biological systems. The tests, often called preclinical research activities. 

On the other hand, small start-up companies focused intensely and entirely on what they were created to do, with the incentive that early and even later employees would be well rewarded if the venture was successful. It was clear to me, in this case, that if the translation from basic and preclinical research to clinical trials were to occur, our best chance was to initiate a company. For the most part, big pharmaceutical houses have stayed clear of allosteric effectors as drugs. We had the enormous advantage that far more is known about hemoglobin as an allosteric protein than any other. 

The questions of whether psychological signs and symptoms of depression are also related to hypersecretion of CRH and vasopressin and how antidepressants work to remedy both the neuroendocrine and the behavioral aspect of this dysregulation have been the subject of intense preclinical research. 

Although somewhat outside the scope of this text, a non-pharmacological treatment that may become an important therapeutic tool in the future deserves to be mentioned within this outlook section. Initial clinical data indicate that depressive patients are significantly improved after TMS treatment and the procedure is very well tolerated (Berman et til., 2000 McNamara et ul.. 2001). Interestingly for preclinical research, repeated TMS in rats has also been shown to have an antidepressant-like effect (Sachdev et ul., 2002) in the forced swim test described later in this chapter. Whether or not there are psychopharmacological correlates of TMS is unknown at present. 

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