Activity on Animals

Notably, a series of organogold(III) DAMP compounds (DAMP = 2-[[(dimethy-lamino)methyl]phenyl]) (Fig. 11) exhibited encouraging anticancer activity in vitro [69,70]. Moreover, these studies also demonstrated that the organometallic compounds possess moderate pharmacological activity on animal models. 

The inhalation toxicity of NF on animals has been studied extensively (37—40). These studies provide the basis of emergency exposure limits (EEL) that have been proposed for NE. The NAS—NRC Committee on Toxicology recommends that the EEL for NE be 10 min at 2250 ppm, 30 min at 750 ppm, and 60 min at 375 ppm. Gaseous NE is considered to be innocuous to the skin and a minor irritant to the eyes and mucous membranes. NE does give a weakly positive metabotically activated Ames test but only at concentrations greater than 2% or 10 times the 10 minute EEL. 

FIGURE 25.9 Fatty add synthase in animals contains all the functional groups and enzyme activities on a single multifunctional subunit. The active enzyme Is a head-to-tall dimer of Identical subunits. (Adapted from Wakit, S. J., Stoops,... 

Pentylenetetrazol (188) is a drug with profound stimulatory activity on the central nervous system. As such, the agent was at one time used in shock therapy for treatment of mental disease. Although it has since been supplanted by safer methods, the agents still occupy an important role in various experimental animal models in pharmacology. Addition of hydrazine to the imino ether (186) obtained from caprolactam affords 187. Treat-... 

Figure 7.7 Dopamine-induced rotation in the rat in which one (left) nigrostriatal dopamine pathway from the substantia nigra (SN) to the caudate putamen (CP) has been lesioned by a prior injection (14 days) of 6-hydroxydopamine. Amphetamine, an indirectly acting amine, releases DA and so can only act on the right side. Since the animal moves away from the dominating active side it induces ipsilateral rotation (i.e. towards the lesioned side). By contrast, the development of postS5maptic supersensitivity to DA on the lesioned side ensures that apomorphine, a directly acting agonist, is actually more active on that side and so the animal turns away from it (contralateral rotation)...

A series of novel l-substituted-4-phenyl-l,2,3-triazolo(4,3-a)quinazolin-5(4H)-ones 1 were synthesized by the cyclization of 2-hydrazino-3-phenyl-quinazolin-4(3H) 2 with various one carbon donors. The starting material 2-hydrazino-3-phenylquinazolin-4(3H)-one 2, was synthesized from aniline 7 by a novel innovative route. When tested for their in vivo Hi-antihistaminic activity on conscious guinea pigs all the test compounds protected the animals from histamine-induced bronchospasm significantly, whereas the compound l-methyl-4-phenyl-l,2,3-triazolo(4,3-a)quinazolin-5(4H)-one lb (percentage protection 70.7%) was found to be equipotent with the reference standard chlorpheniramine maleate (percentage protection 71%). These compounds show negligible sedation (5%) when compared to the reference standard (26%). Hence they could serve as prototype molecules for future development [1,4,5]. 

Benzo(c)phenanthrene (BcP) is exceptionally weak or inactive as a carcinogen in experimental animals (51). On the other hand, the bay region anti diol epoxide of BcP (14) exhibits high tumor initiating activity on mouse skin (65). 

Bazedoxifene s primary indication is the treatment and prevention of postmenopausal osteoporosis (Miller et al. 2002). In animal models bazedoxifene displays estrogenhke agonistic activity on bone loss and significantly reduces total cholesterol levels with doses as low as 0.1 mg/kg (Miller et al. 2002). Also in these models, there is no evidence of an estrogenic stimulatory effect on the endometrial epithelial cell (Miller et al. 2001). 

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