Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of mepyramine, ketotifen and picumast (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarin dihydrochloride) on anaphylactic histamine release from lungs, heart, stomach, and intestine of guinea pigs in response to antigen was examined in vivo. When sensitized animals were pretreated intraperitoneally with a single dose of these compounds 60 min before i.v. antigen challenge (native ovalbumin 20 mg/kg), a dose related inhibition of immunological histamine release from the lung was established. After pretreatment of the animals with 3 mg/kg of mepyramine, 10 mg/kg of ketotifen, and 6 mg/kg of picumast dihydrochloride, the inhibitory effect on histamine release from the lung was so marked that both the acute and the protracted anaphylactic shock were completely suppressed. The corresponding histamine levels in blood plasma, regularly measured 1.5 min after antigen stimulation, had dropped to about 40%, 50%, and 35%, respectively (p less than 0.05), whereas lung histamine content increased by about 60%, 150%, and 90% compared with unpretreated, shocked controls. According to these findings the number of lung mast cells in protected animals was significantly increased. In addition, ketotifen significantly reduced histamine release from heart and intestine. In contrast the compound injected intravenously 1 min before antigen challenge had no effect on mast cell degranulation and on histamine liberation, thus only decreasing the acute anaphylactic bronchospasm. These data suggest that all three drugs were acting as H1-antagonists when administered immediately prior to the antigen-provoked anaphylactic reaction. The property of these drugs to inhibit mast cell degranulation and the reduction of mediator release, however, appears to depend on their prolonged action on these cells. Together with their histamine antagonism anaphylactic death is thus prevented.
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PMID:Inhibition of immunological histamine release from guinea pig lungs and other organs by mepyramine, ketotifen, and picumast in vivo. 248 12

Picumast dihydrochloride (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarin dihydrochloride) was compared with cromoglycate, ketotifen and mepyramine as an inhibitor of allergic and anaphylactoid reactions. 1. In guinea-pigs, pretreatment with picumast dihydrochloride given intravenously, orally or by inhalation prevented bronchospasm induced by antigen or histamine. The fraction of the bronchospasm remaining after mepyramine pretreatment was further reduced by picumast dihydrochloride. 2. Systemic administration of picumast dihydrochloride inhibited antigen-induced conjunctivitis, whereas mepyramine and ketotifen were inactive. 3. Intravenous and oral pretreatment with picumast dihydrochloride inhibited the antigen-induced mast cell degranulation in rat mesentery. The effective doses of cromoglycate given intravenously were twice as high as those of picumast dihydrochloride. Picumast dihydrochloride did not inhibit antigen-induced bronchoconstriction in rats. 4. The cutaneous reaction induced with Ascaris antigen in atopic monkeys was insensitive to the antihistaminic action of ketotifen, whereas it was inhibited by low doses of picumast dihydrochloride. Both compounds suppressed skin reactions induced by histamine. 5. Picumast dihydrochloride decreased IgE production in atopic high responder mice. It did not prevent autoimmune nephritis in NZB/W mice. 6. In rats, picumast dihydrochloride did not reduce cotton pellet granuloma, nor adjuvant arthritis. The inhibition of carrageenin oedema is presumably due to its anti-oedematous properties rather than to an antiproliferative activity. In conclusion, the inhibition of allergic and anaphylactoid reactions by picumast dihydrochloride can be attributed to a combined inhibition of liberation and action of histamine and other mediators.
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PMID:Antiallergic activity of picumast dihydrochloride in several animal species. 257 54

In a small range finding study a number of N-benzylpiperazino derivates of 3-nitro-4-hydroxycoumarin have been shown to combine potent H1-antihistamine activity with that of mast cell stabilization as demonstrated by their activity as antagonists of histamine on guinea pig ileum and by their inhibition of the release of histamine in rat passive peritoneal anaphylaxis (PPA). The most potent compound, 1-[2-hydroxy-3-[(4-hydroxy-3-nitrocoumarin-7-yl)oxy]propyl]-4- (4-chlorobenzyl)piperazine, 30, had a pA2 of 9.0 against histamine on guinea pig ileum and inhibited histamine release in the rat PPA test with a potency similar to that of disodium cromoglycate.
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PMID:N-benzylpiperazino derivatives of 3-nitro-4-hydroxycoumarin with H1 antihistamine and mast cell stabilizing properties. 620 60