Histamine and homologous compounds

Theoretical Study of the Proton Affinities of Some Substituted Derivatives of Histamine and Homologous Compounds. Structure-Activity Relationships... 

Theoretical study of the proton affinities of some substituted derivatives of histamine and homologous compounds. Structure-activity relationships... 

PDE IV inhibitors, as well as some combined PDE IIl/IV inhibitors, are currently under development for the treatment of asthma (Christensen and Torphy, 1994 Nicholson and Shahid, 1994). The basis for this development includes bronchodilatory activity directly related to inhibition of PDE IV, and/or PDE III, in airway smooth muscle, as well as the antiinflammatory activity of these compounds. PDE IV is the major cAMP PDE isozyme present in inflammatory cell types and inhibition of PDE IV has been linked to elevation of cAMP and inhibition of histamine or leukotriene release from mast cells, inhibition of oxygen free radical release from eosinophils or neutrophils, inhibition of adhesion, migration, or activation of eosinophils, and inhibition of TNF-a release from human monocytes (see Nicholson and Shahid, 1994, or Christensen and Torphy, 1994, for some reviews). There are now known to be at least four sub-types of PDE IV that are encoded by different cDNAs (Bolger et al., 1993 Davis et al, 1989 Livi et al., 1990). Although sequence homology of 75-90% is evident among subtypes, key differences, as well as cellular distribution, are apparent. Currently there are no selective inhibitors of the PDE IV subtypes. 

The concentration of surfactant required to inhibit DNA synthesis was always lower than that required to release histamine from most cells which was lower in turn than the concentration required for fibroblast lysis, measured by release of Cr. In many studies of homologous series of surfactants, compounds with a Cl2 carbon chain appear to be optimally active. The same trend is shown here in the sodium caprylate-sodium palmitate series. Similar reports of the efficacy of the laurate ion in inducing skin irritancy have appeared, but Ferguson and Prottey do not claim that their test systems are indicators of irritancy. The molecular basis for the activity of the C12 hydrocarbon-chain surfactants is of considerable interest, however. Table 10.19 from a review of the molecular basis... 

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