A pharmacologic study on the histamine releasing effect of atracurium and other muscle relaxants in rat isolated ileum

Abstract

In this study, the effects of histamine, antihistamines (terfenadine and mepyramine), 5-hydroxytryptamine, and muscle relaxants, atracurium, vecuronium and gallamine, on the tone and contractility of rat ileum were studied and compared in vitro. The aim of the present investigation was to measure, pharmacologically, the histamine releasing effect of muscle relaxants, e.g atracurium, vecuronium and gallamine, by comparing their contractile response in the absence and presence of antihistamines and comparing their mechanical responses with those produced by histamine and 5-hydroxytryptamine (5-HT). The results showed that the antihistamines, triludan(terfenadine) and mepyramine produced opposite effects in rat ileum. Terfenadine (0.1-20 microM) produced concentration-dependent contractions in the rat ileum, whereas mepyramine (0.1-10 microM) relaxed the muscle, e.g. by 1.2 g tension. Atracurium (0.5-500 microM), vecuronium (0.2-200 microM), and gallamine (0.1-7.0 microM) produced marked contractions (1.5-4.0 g tension) in rat ileum, and these contractions were markedly reduced by mepyramine (1.3 microM) or terfenadine (5 microM), implicating histamine release in the generation of these contractions. However, there was some residual contraction which was not blocked by mepyramine, but by 5-HT antagonist, methysergide (1 microM), indicating that a mechanism other than histamine release may be responsible for the residual contraction, i.e. release of other mediators such as 5-HT, prostaglandins, or calcium. 5-HT (0.5-500 microM) and histamine (0.5-500 microM) produced contractions in the rat ileum, but 5-HT was more effective than histamine in producing these contractions. Similarly, gall amine was more effective than atracurium and vecuronium in contracting the rat ileum.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of the potentiation of neurally‐induced bronchoconstriction by gallamine in the guinea‐pig

“…Another possible action of gallamine that must be taken into account is histamine release. In fact, gallamine (0.1-7 .M) produces marked contractions of rat isolated ileum, which are reduced by antihistamines (Wali et al, 1987). Although it is unlikely that gallamine releases large amounts of histamine from the guinea-pig airways, since it does not cause, given alone, any bronchoconstriction (data not shown), it could release subthreshold quantities, acting synergistically with ACh released during vagal stimulation.…”

“…that the potentiating action of gallamine on the bronchoconstriction may be due to additional effects of this drug, such as the inhibition of the sympathetic nervous system (possibly due to its ganglion blocking activity, Bowman & Webb, 1972) and histamine release (Wali et al, 1987) or to an increased release of neuropeptides, which are known to be mobilized by vagal stimulation, under certain experimental conditions, from airway sensory neurones (Lundberg et al, 1983). In order to obtain a deeper insight into the mechanism and the physiopathological relevance of the potentiating action of gallamine, we also examined the effects of this agent on the bronchoconstriction induced by endogenous ACh accumulation as a result of acetylcholinesterase inhibition and anaphylactic challenge.…”