Rat passive cutaneous anaphylaxis

KAWABATA, T.T. BABCOCK, L.S. (1993) Measurement of murine ovalbumin-specific IgE by a rat basophil leukemia cell serotonin release assay. Comparison to the rat passive cutaneous anaphylaxis assay. Journal of Immunological Methods, 162, 9-15. 

The antiallergy activity of the pyrimido[4,5-b]quinolines was determined using the 48-hour IgE-mediated rat passive cutaneous anaphylaxis (PCA) procedure (6,2), which is widely used as a screen to identify agents with a pharmacological profile similar to intal. The compounds were administered to groups of 5 to 7 rats either intravenously in saline at pH 7.2-8.0 or orally in an aqueous solution near physiological pH (fi). Since these compounds did not demonstrate antagonism toward the anaphylactic mediators, histamine and serotonin, their activity is an indication of inhibition of mediator release. 

Table I. Relative Potencies against Rat Passive Cutaneous Anaphylaxis (PCA) of 3-(IH-Tetrazo1-5-yl)-chromones i 3-( -Oxo-4H-l-benzopyran-3)-acrylic Acids (4), and DSCG...

Comments on the Studies in Rats. Passive cutaneous anaphylaxis in rats has been used extensively in the study of cromo-glycate-like compounds. Upon intravenous administration these compounds can abolish the vascular permeability changes, which follow mediator release from sensitized mast cells. This activity appears at doses which do not inhibit the effects of exogenous mediators. The oral activity of this type of compounds is generally nil and this holds also for doxanthrazole, which was inactive in the standard conditions of our test. 

Chloro-oxazolo[4,5-/i]quinoline-2-carboxylic acid methyl ester was the most active compound in tests for inhibitors of antigen-induced release of histamine in vitro from rat peritoneal mast cells (IC50 of 0.3 p,M) and as inhibitors of IgE-mediated passive cutaneous anaphylaxis in the rat (ED50 (intraperitoneal) of 0.1 mg/kg in dose 0.5 mg/kg as an inhibitor of the test)—10 times and 60 times more potent, respectively, than the disodium salt of cromoglycic acid (85JMC1255). 

The synthetic P-o-glucopyranoside 30 was converted to the cyanoglucoside rho-diocyanoside A (38a), which was isolated from the underground part of Rhodiola quadrifida (Pall.) Fisch. et Mey. (Crassulaceae) and found to show antiallergic activity in a passive cutaneous anaphylaxis test in rat. Acetylation of 30 gave an acetate (98% yield) which was subjected to ozonolysis to afford the aldehyde 39. The Horner-Emmons reaction of 39 using diethyl (l-cyanoethyl)phosphonate furnished (Z)-40a (32% yield from 30) and ( )-40b (10% yield from 30). The physical... 

Passive cutaneous anaphylaxis inhibition. Acetone extract of the dried rhizome, administered intragastrically to rats at a dose of 200 mg/kg, was active vs IgE-sensitized animals . 

In addition to these chemotherapeutic indications, some pharmacodynamic uses are indicated. 4-Amino-3-o-chlorobenzyltriazole-5-carboxamide and related compounds are claimed as useful anticonvulsants (84JAP118775). 5-Butoxycarbonyl-2-(Af-3-piperidinopropyl)-4-p-toluidinotriazole (89) is claimed as a potent vasodilator (83GEP3134842). lH-Triazolo[4,5-b]quinol-4-one (99) is claimed to inhibit passive cutaneous anaphylaxis in rats and to be of interest in treating human asthma [80EUP(A)2562]. 

Inagaki, N., Miura, T., Daikoku, M., Nagai, H. and Koda, A. (1989). Inhibitory effects of jS-adrenergic stimulants on increased vascular permeability caused by passive cutaneous anaphylaxis, allergic mediators, and mediator releasers in rats. Pharmacology 39, 19-27. 

Structure activity relationships for a series of chromone-2-carboxylic acids, of which FPL 52791 (21) showed efficacy in passive cutaneous anaphylaxis (PCA) (rat) both by intravenous and oral administration, have been published. Substitution in ring A shows that 6,8-di-t-butyl (12 x DSCG)>6,8-di-Et>6,8-di-Me monosubstitution.7 Clinical studies of 21 are in progress. Similarly, in a series of chromones with a tetrazolyl moiety at the 2 or 3 position, (22) was the most potent in the PCA (rat), both orally and i.v. (—11.6 x DSCG). The following structure activity relationships were noted (a) the 3-tetrazolyl... 

Rats dosed twice with inhibiting doses of either DSCG or lodoxamide tromethamine show tachyphylaxis to an inhibition of the subsequent passive cutaneous anaphylaxis assay (10.11,13 16,17). Atropine (25 mg/kg) or QNB (0.01 mg/kg) given ip 20 min prior to the first iv dose of DSCG or lodoxamide, partially blocked this multiple dose tachyphylaxis (13,16,17,27). Atropine or QNB by themselves at these concentrations had no inhibitory effect on the PCA reaction, but markedlv reduced (or almost totally eliminated) the tachyphylaxis (Fig. 3,4) to DSCG and to a lesser... 

The sensitizing capacity of the serum from allergic subjects has been known since the classical transfer experiments of Prausnitz-Ktlstner. Passive cutaneous anaphylaxis in the rat is essentially identical to the reaction of Prausnitz-KUstner. A skin area of normal rats is sensitized to an allergen by the local injection of serum containing specific IgE-antibodies and appropriate... 

There are other compounds in the literature which seem to have a potentially useful blend of bronchodilator and antiallergy action. Compound IX, having a cromolyn-type structure, is effective in the passive cutaneous anaphylaxis test in rats as well as in the histamine aerosol test in guinea pigs (22). It has less cardiovascular effects than theophylline but causes some CNS stimulation. Compound X is a recent compound which in animals appears to be more potent than theophylline in its bronchodilator/antiallergic actions and also appears to have greater broncho-selectivity (23, 24). 

A study of primary IgE antibody production is performed by immunizing the mice with alum precipitated HEA. Two doses of antigen are used 1 //g and 100 g. The titre of IgE antibody is evaluated by heterologous passive cutaneous anaphylaxis in rat skin . High responders injected with the high... 

It also inhibits rat reaginic passive cutaneous anaphylaxis... 

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