Guinea pig anaphylaxis

The results obtained in the guinea-pig anaphylaxis test after oral oxatomide administration are presented in Fig. 1. A dose-dependent increase in the number of animals protected from the acute anaphylactic shock was observed and the histamine-induced paw oedema was similarly reduced by increasing doses of oxatomide. As previously found with cinnarizine, protection from anaphylactic shock was a more sensitive measure of the activity of oxatomide than was the reduction of paw oedema. In comparison with cinnarizine, however, oxatomide was considerably more potent. The calculated ED5o s, 2 h after oral administration, were 0. 16(0. 081 - 0. 31) mg/kg for protection from anaphylactic shock and 0. 30(0. 18 - 0. 50) mg/kg for inhibition of histamine oedema. 

Figure 1. Individual survival time and histamine oedema after oral oxatomide administration (t 2 hr) in the guinea pig anaphylaxis test...

In Table VI a and b the results of 56 oxatomide analogues (36 benzimidazolones and 20 benzimidazoles) are summarized. All compounds were tested at a standard dose of 10 mg/kg. In particular those compounds are active which showed the highest activity in guinea-pig anaphylaxis and histamine oedema, e. g. the benzimidazolones 8, 9, 10, 13, 14, 23, 24 and 25 and the benzimidazoles 48, 61 and 62. However, no linear correlation was found. 

Oxatomide has been selected from a new chemical series of benzimidazolones and benzimidazoles on the basis of its activity on hypersensitivity and histamine-induced reactions in three species, the guinea-pig, the rat and the dog. In a well-known model, the guinea-pig anaphylaxis, oxatomide was at least as effective on the anaphylactic shock as on the histamine oedema induced in the same animals. In the rat, the new compound was an orally active inhibitor of PCA-reactions. Compound 48/80-induced lethal shock was prevented at doses of the same order as those required to inhibit histamine skin reactions. In the dog inhibition of allergic reactions, induced by Ascaris allergens in the skin of hypersensitive dogs, inhibition of histamine skin reactions and reduction of circulating histamine released by Cremophor EL were obtained by virtually the same oral doses. 

The induction of antibody formation in animals is not predictive of a potential for antibody formation in humans. Humans may develop serum antibodies against humanised proteins, and frequently the therapeutic response persists in their presence. The occurrence of severe anaphylactic responses to recombinant proteins is rare in humans. In this regard, the results of guinea pig anaphylaxis tests, which are generally positive for protein products, are not predictive for reactions in humans therefore, such studies are considered of little value for the routine evaluation of these types of products. 

Ishii, A., Nakagawa, T., Nambia, F., Motoishi, M. and Miyarioto, T. (1990). Inhibition of endc enous leukotriene-mediated lung anaphylaxis in guinea-pigs by a novel receptor ant gonist ONO-1078. Int. Arch. Allergy Immunol. 22, 404-407. 

Payne, A.N., Garland, L.G., Lees, I.W. and Salmon, J.A. (1988). Selective inhibition of arachidonate 5-lipoxygenase by novel acetohydroxamic acids effects on bronchial anaphylaxis in anaesthetised guinea-pigs. Br. J. Pharmacol. 94, 540-546. 

In the 1930s an unknown material was hypothesized that was proposed to cause a slow and sustained contraction of smooth muscle. It was named the slow reacting substance (SRS). By 1940 a similar substance was reported to be found in guinea pig lungs and was called the slow reacting substance of anaphylaxis (SRS-A). Over the next 40 years, while no one could isolate, characterize, or synthesize this mate-... 

Amino-substituted naphthoquinones and heterocyclic variants have been disclosed in the patent literature as 5-LO inhibitors. Compounds represented by (80) (X = C, N) from Lilly inhibited SRS-A release from sensitized guinea-pig lung tissue [218]. Similar compounds such as (81) (R = carboxylic ester, acyl, or aryl) and related naphthalene derivatives, from American Cyanamid, gave good inhibition in guinea-pig ISN (at 10 //g/ml) and in passive cutaneous anaphylaxis in mice (25-60 /zM i.p.) [219,220]. 

Li et al. (1994) examined the effects of chloroform administered in drinking water to guinea pigs with cedar pollen-induced allergic conjunctivitis, prepared by passive cutaneous anaphylaxis. Groups of 5 male... 

Devey, M.E., Anderson, K.J., and Coombs, R.R.A. 1976. The modified anaphylaxis hypothesis for cot death. Anaphylactic sensitisation in guinea pigs fed cow s milk. Clin Exp Immunol 26 542-548. 

In mucosal sheets from porcine ileum, the delta opioid agonist DPDPE inhibits saxitoxin-sensitive elevations in neurogenic ion transport evoked by histamine [142], tryptase-like enzymes [143], serotonin [144], kallidin [145], and type I hypersensitivity [142]. These effects of DPDPE are inhibited by naltrindole. In contrast, elevations in neurogenic ion transport occurring secondary to an immediate hypersensivity reaction in the guinea pig ileal mucosa are augmented by DPDPE, indicating that the neuromodulatory actions of opioids on active mucosal transport evoked by inflammation or anaphylaxis may depend on the species examined [146],... 

Verdier F, Chazal I, Descotes J. Anaphylaxis models in the guinea-pig. Toxicology 1994 93 55-61. 

Typical protocols for dermal sensitization, active systemic anaphylaxis, and passive cutaneous anaphylaxis tests are given in the article Animals in Drug Development, in this encyclopedia. In a typical gel-diffusion test, solutions of test compound, egg albumin (positive control), or vehicle (usually saline) are mixed with complete Freund s adjuvant. These mixtures are injected into animals (usually guinea pigs) of the... 

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