Bronchial effects of some prostaglandin E and F analogues.

Abstract

AbstractThe effects of some analogues of PGE1, PGE2 and PGF2α, rendered less accessible to the action of prostaglandin dehydrogenase by having methyl groups at carbons 15 and/or 16, or a phenyl group at carbon 17, on the tracheobronchial insufflation pressure in guinea pigs and on the tone of isolated human bronchi were investigated. Regardless of route of administration, i.v. injection or aerosol administration, PGE1,16,16‐dimethyl‐PGE1, PGE2, the methyl esters of 15(R)15‐methyl‐PGE2 and 15(S)15‐methyl‐PGE2, 16,16‐dimethyl‐PGE2 and its methyl ester, and 17‐phenyl PGE2 all produced a dose‐dependent inhibition of the histamine‐induced increase in insufflation pressure and a fall in systemic blood pressure in the anesthetized guinea pig. Although the duration of action of the PGE‐analogues was longer than that of the parent compounds, none of them was more potent with regard to the peak effect produced on insufflation pressure. Of the PGF2α analogues studied, 16,16‐dimethyl‐PGF2α was the most potent compound, in decreasing rank order followed by 15(S)15‐methyl‐PGF2α, 17‐phenyl‐PGF2α and PGF2α, in eliciting an increase in insufflation pressure on i.v. injection. On aerosol administration, only 16,16‐dimethyl‐PGF2α compound was more potent than PGF2α On isolated human bronchi, PGE1 and PGE2 were consistently relaxant, although in some expts. the relation to PGE2 was followed by constriction. The 16,16‐dimethyl analogues of PGE1 and PGE2 were consistently bronchoconstrictor whereas the effects of the other PGE–analogues were weak and inconsistent. In comparison with the bronchorelaxant β2‐adrenoceptor stimulating compounds, the PGEs and PGE‐analogues studied do not have any outstanding features and may even imply a risk in clinical practice.