Animal Models study

Amine boranes have been examined by a variety of spectroscopic methods (24—29). The boron-substituted alpha-amino acids have been utilized in animal model studies. These compounds along with their precursors and selected derivatives have been shown to possess antineoplastic, antiarthritic, and hypolipidemic activity (30—32). The boron amino acid analogues are also being evaluated for possible utility in boron neutron capture therapy (BNCT) (33). 

In-vitro models can provide preliminary insights into some pharmacodynamic aspects. For example, cultured Caco 2 cell lines (derived from a human colorectal carcinoma) may be used to simulate intestinal absorption behaviour, while cultured hepatic cell lines are available for metabolic studies. However, a comprehensive understanding of the pharmacokinetic effects vfill require the use of in-vivo animal studies, where the drug levels in various tissues can be measured after different dosages and time intervals. Radioactively labelled drugs (carbon-14) may be used to facilitate detection. Animal model studies of human biopharmaceutical products may be compromised by immune responses that would not be expected when actually treating human subjects. 

As alluded to already, a major problem inherent in neuropharmacologic research is the lack of phenotypic changes that are clearly associated with treatment response this difficulty is particularly evident for mood-stabilizing agents [9]. In the absence of suitable animal models, studies have attempted to overcome this experimental hurdle by employing paradigms that involve the identification of com-... 

Once again, clinical studies reveal a divergence between potency and qualitative effect. No in vitro or animal model studies have yet indicated any major difference between oxygen at the 4-position and its sulfur isostere, although there are changes in their experimentally measured ionization potentials (54). 

The structure activity relationship (SAR) and animal model studies of biaryl benzamide MTP inhibitors 3 and 4 have also been reported. Compound 3 has an IC50 of 0.5 nM against human MTP in an in vitro assay and showed normalization of plasma lipoprotein levels in Watanabe-heritable hyperlipidemic rabbits,... 

Diaminoindane 4 has an IC50 of 0.7 nM in the in vitro MTP inhibition assay, and has shown in vivo efficacy in various animal model studies [15]. No clinical trials of 4 have been reported. 

The aim of this chapter is to highlight recent advances in fractionation techniques for grape seed PAs, using as examples methods we are using for large-scale fractionation into monomers, oligomers, and polymers for assessment of bioactivity and bioavailability in animal model studies of Alzheimer s disease. Our methods represent modifications/combinations of previously described approaches. We first discuss the available methods and modifications and then present a case study for the fractionation of MegaNatural-AZ GSE. 

Braff DL, Geyer MA Sensorimotor gating and schizophrenia human and animal model studies. Arch Gen Psychiatry 47 181-188, 1990 Bramanti P, Bianchi L, Benedetto M, et al Study of the hypnic effect of amineptine evaluation by polygraphy and tests. Prog Neuropsychopharmacol Biol Psychiatry 9 157-165, 1985... 

In the hope of developing either a more effective agent or one with fewer adverse effects, medicinal chemists have synthesized a number of new compounds. Preclinical animal model studies are used to select potentially useful drugs, using a profile of pharmacological properties reflecting differential blockade of dopamine, as well as other neurotransmitter systems (e.g., 5-HT). This research has led to the development of several new classes, as noted earlier in this chapter. 

Alpha-1 Receptors. A primary location of these receptors is the smooth muscle located in various tissues throughout the body. Alpha-1 receptors are located on the smooth muscle located in the peripheral vasculature, intestinal wall, radial muscle of the iris, ureters, urinary sphincter, and spleen capsule. The response of each tissue when the alpha-1 receptor is stimulated varies depending on the tissue (see Table 18-2). Research also suggests that there might be three subtypes of alpha-1 receptors, identified as alpha-1 A, alpha-IB, and alpha-ID receptors.4 Much of this research, however, has focused on the characteristics of alpha-1 receptor subtypes in various animal models. Studies are currently underway to determine the exact location and functional significance of these alpha-1 receptor subtypes in humans. 

In recent years, a few fermented dairy products with naturally occurring antihypertensive peptides have been launched in both the Japanese and Finnish market. The Japanese sour milk product Calpis is made by inoculating skim milk with a starter containing L. helveticus and S. cerevisiae. The fermented drink is rich in the peptides Val-Pro-Pro and Ile-Pro-Pro, which have proven to lower blood pressure both in animal model studies and in clinical trials with hypertensive humans (Takano 2002). 

Although extensive in vitro testing is performed on each immunotoxin to assess its cytotoxicity and specificity, it is animal model studies that ultimately determine the serum half-life, serum stability, as well as the efficacy of an immunotoxin. A compilation of the in vitro and in vivo data enables a decision to be made on the potential of each immunotoxin to be an effective and safe therapeutic and to determine whether human clinical trials are warranted. 

Braff DL, Geyer MA. 1990. Sensorimotor gating and schizophrenia. Human and animal model studies. Arch Gen Psychiatry 47 181-188. 

The rapid development of carborane chemistry is mainly due to their practical applications. For instance, the potential utility of carborane polymers as gaskets, O-rings, and electrical connector inserts has been reported. Their functionality for solvent extraction of radionuchdes as well as the potential medicinal value of the isoelectronic and isostructural boron analogues of biologically important molecules has been the subject of many review articles. For example, a number of boron compounds have been found to possess anti-inflammatory and antiarthritic activity in animal model studies. Boron compounds have also been implicated in studies designed to probe the importance of the so-called anionic subsite of acetylcholine esterase and Ach receptors. But, by far the most interesting practical apphcations of carboranes are in areas of boron neutron capture therapy (BNCT) and supramolecular assembly. 

Several animal model studies have focused on the immime response to infection and also to vaccination. Most studies identify antibody titer, but some also show cytokine production or possible mechanisms of bacterial evasion. A focus on immime response studies will help to further define B. anthracis pathogenesis and provide insight into the design of future vaccines and therapeutics. Most countermeasure studies have been conducted on vaccines, as antibiotic studies have typically been performed in vitro. Primary concerns are the length of required treatment, effieient prophylaxis methods, and less complicated dosing regimens for vaccines. In a theoretical bioterrorist attack scenario, it will be essential to distribute effective treatment and prophylaxis to infected or potentially exposed persons in an expedient manner. 

---