Efficacy screening animal models

The primary goal during candidate screening is to rank a large number of compounds based on efficacy in animal models, biopharmaceutical properties (such as solubility and permeability in caco-2 cells), preliminary pharmacokinetic profile in animals, and potential for metabolic and toxicity liability. A non-good laboratory practice (GLP) Ames test may be performed to screen for potential mutagenicity. 

PHARMACOLOGICAL EFFECTS The antiseizure properties of valproic acid (DEPAKENE, others) were discovered serendipitously when it was employed as a vehicle for other compounds that were being screened for antiseizure activity. Its efficacy in animal models parallels its efficacy against absence as well as partial and generalized tonic-clonic seizures in humans. 

The committee considers the threat of a terrorist incident involving T-2 mycotoxin to be very low. In addition, its effects are not consistently fatal, nor are they so rapid that prehospital treatment is demanded. The committee therefore recommends that civilian medical personnel continue to rely on nonspecific treatment and supportive therapy. R D in this area should be limited to screening antivesicant treatments for their efficacy in animal models of mycotoxin poisoning. 

As the drug discovery process increased in intensity in the mid- to late 20th century, primarily as a result of the major screening and chemical synthetic efforts in the pharmaceutical industry in industrialized countries worldwide, but also as a result of the biotechnology revolution, the need for increased sophistication and efficacy in (1) how to discover new drugs, (2) how to reproducibly prepare bulk chemicals, (3) how to determine the activity and safety of new drug candidates in preclinical animal models prior to their... 

During the first half of the century, there was virtually an exclusive reliance on animal testing as the primary model for drug discovery and development. New chemical entities were administered to rodents in the primary screen assay, and the appropriate responses were monitored for indications of therapeutic potential. Compounds meeting the appropriate potency and efficacy criteria were promoted to more diverse and sophisticated animal models to characterize their pharmacological profile. The responses that were monitored included blood pressure (hypotensives), latency to respond to painful stimuli (analgesics), attenuation of seizure propensity (antiepileptics) and other responses that were intuitively and pharmacologically valid indicators of medicinal potential or toxicity. Some of these methods were semiautomated and quite sophisticated for their time, particularly for cardiovascular indications [1]. 

Animal models also provide a means for testing novel compounds and can be beneficial screening devices for new therapeutics and medications. Several studies have explored the efficacy of various compounds in enhancing ERP components and gating and in reversing schizophrenia-like deficits in a variety of models. 

Once the drugs are screened using appropriate methods, promising new compounds need to be tested in animal models for their safety, dose and efficacy. It is very important to remeniber that platelets of different species vary widely in their responses to agonists (91, also discussed in other chapters). For instance, majority of dogs have platelets that do not respond to AA with aggregation (50). However, when these AA refiactory platelets are... 

After the introduction of the first neuroleptic drugs, many animal models were developed to screen new compounds for potential antipsychotic activity. These models predict both antipsychotic efficacy and side effect liability in humans (104-106). Other animal models at-... 

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