Antiallergic effects of the adrenergic beta-stimulant trimetoquinol in rats and guinea pigs.

Abstract

Trimetoquinol (TMQ), like isoproterenol (Iso), inhibited not only the in vitro anaphylactic release of histamine from minced guinea pig lung tissue but also passive cutaneous anaphylaxis (PCA) in rats and guinea pigs and systemic anaphylaxis in guinea pigs. In these inhibitory effects, TMQ was more potent than Iso and other β-adrenergic stimulants (orciprenaline, salbutamol and terbutaline) in vivo, and 1000 times more active than disodium cromoglycate in vitro. In rat PCA, orally administered TMQ was fully effective as early as 5 min after administration and showed a longer duration of action than Iso. Furthermore, TMQ did not greatly affect the vascular permeability, unlike Iso, which markedly inhibited histamine-induced dye leakage on the rat skin, suggesting that the inhibition of PCA by Iso may be partly ascribed to this action on the capillary vessels, and therefore that the anti-anaphylactic activity of TMQ should be that much greater than that of Iso. When rat mast cells were incubated with TMQ, the cellular level of adenosine-3', 5'-cyclic monophosphate (cAMP) was elevated. The inhibition of in vitro histamine release by TMQ and the elevation of cAMP in the mast cells by TMQ and Iso were both antagonized by propranolol, but not by practolol. These results indicate that TMQ and Iso inhibit the anaphylactic reactions by β-adrenergic mechanisms, probably of a β2-type.