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Antiallergic activity profile in vitro of RHC 2963 and related compounds.
Int J Immunopharmacol. 1983; 5(6):491-502.IJ

Abstract

RHC 2963 (7-methyl-pyrido (3',2':4,5)-thieno (3,2-d)-1,2,3 triazine-4(3H)-one and 20 related compounds have been investigated for their antiallergic activities in 3 in vitro models of anaphylaxis and for their effects on cyclic nucleotide phosphodiesterases (cNUC-PDE) from purified rat mast cells (RMC). Nine compounds were potent (I50 less than or equal to 80 microM) inhibitors of antigen-induced release of histamine (AIR) from RMC, 2 compounds inhibited anti-IgE-induced release of histamine from human basophils (I50 less than or equal to 60 microM) and one compound inhibited AIR from guinea pig lung slices (I50 = 55 microM). RHC 2963 was 18 times more potent than disodium cromoglycate (DSCG) as inhibitor of AIR from RMC and had an activity profile identical to that of DSCG in the following respects: loss of inhibitory activity with increasing preincubation time, tachyphylactic properties and inability to inhibit non-immunologic release of histamine induced by compound 48/80. Neither RHC 2963 nor DSCG had any effect on anti-IgE-induced release of histamine from human basophils or IgG1-mediated release of histamine from guinea pig lung. Twelve of the compounds in this chemical series were more potent than theophylline as inhibitors of cyclic AMP and/or cyclic GMP phosphodiesterase (PDE) from RMC. Paired regression analysis of the I50 values for inhibition of AIR and cNUC-PDE from RMC revealed no statistically significant correlation between the inhibition of AIR and inhibition of cAMP- or cGMP-PDE. We conclude: (1) RHC 2963 and some of the related compounds are potent inhibitors of immunologic release of histamine from RMC with a mechanism of action similar to that of DSCG, and (2) inhibition of cAMP- or cGMP-PDE by these compounds is not the biochemical mechanism by which they inhibit AIR from RMC.

Authors

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Pub Type(s)

Journal Article

Language

eng

PubMed ID

6198298

Citation

Khandwala, A, et al. "Antiallergic Activity Profile in Vitro of RHC 2963 and Related Compounds." International Journal of Immunopharmacology, vol. 5, no. 6, 1983, pp. 491-502.
Khandwala A, Van Inwegen R, Coutts S, et al. Antiallergic activity profile in vitro of RHC 2963 and related compounds. Int J Immunopharmacol. 1983;5(6):491-502.
Khandwala, A., Van Inwegen, R., Coutts, S., Dally-Meade, V., & Youssefyeh, R. D. (1983). Antiallergic activity profile in vitro of RHC 2963 and related compounds. International Journal of Immunopharmacology, 5(6), 491-502.
Khandwala A, et al. Antiallergic Activity Profile in Vitro of RHC 2963 and Related Compounds. Int J Immunopharmacol. 1983;5(6):491-502. PubMed PMID: 6198298.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antiallergic activity profile in vitro of RHC 2963 and related compounds. AU - Khandwala,A, AU - Van Inwegen,R, AU - Coutts,S, AU - Dally-Meade,V, AU - Youssefyeh,R D, PY - 1983/1/1/pubmed PY - 1983/1/1/medline PY - 1983/1/1/entrez SP - 491 EP - 502 JF - International journal of immunopharmacology JO - Int J Immunopharmacol VL - 5 IS - 6 N2 - RHC 2963 (7-methyl-pyrido (3',2':4,5)-thieno (3,2-d)-1,2,3 triazine-4(3H)-one and 20 related compounds have been investigated for their antiallergic activities in 3 in vitro models of anaphylaxis and for their effects on cyclic nucleotide phosphodiesterases (cNUC-PDE) from purified rat mast cells (RMC). Nine compounds were potent (I50 less than or equal to 80 microM) inhibitors of antigen-induced release of histamine (AIR) from RMC, 2 compounds inhibited anti-IgE-induced release of histamine from human basophils (I50 less than or equal to 60 microM) and one compound inhibited AIR from guinea pig lung slices (I50 = 55 microM). RHC 2963 was 18 times more potent than disodium cromoglycate (DSCG) as inhibitor of AIR from RMC and had an activity profile identical to that of DSCG in the following respects: loss of inhibitory activity with increasing preincubation time, tachyphylactic properties and inability to inhibit non-immunologic release of histamine induced by compound 48/80. Neither RHC 2963 nor DSCG had any effect on anti-IgE-induced release of histamine from human basophils or IgG1-mediated release of histamine from guinea pig lung. Twelve of the compounds in this chemical series were more potent than theophylline as inhibitors of cyclic AMP and/or cyclic GMP phosphodiesterase (PDE) from RMC. Paired regression analysis of the I50 values for inhibition of AIR and cNUC-PDE from RMC revealed no statistically significant correlation between the inhibition of AIR and inhibition of cAMP- or cGMP-PDE. We conclude: (1) RHC 2963 and some of the related compounds are potent inhibitors of immunologic release of histamine from RMC with a mechanism of action similar to that of DSCG, and (2) inhibition of cAMP- or cGMP-PDE by these compounds is not the biochemical mechanism by which they inhibit AIR from RMC. SN - 0192-0561 UR - https://www.unboundmedicine.com/medline/citation/6198298/Antiallergic_activity_profile_in_vitro_of_RHC_2963_and_related_compounds_ L2 - https://linkinghub.elsevier.com/retrieve/pii/0192-0561(83)90042-5 DB - PRIME DP - Unbound Medicine ER -