Effect of MB327 and oximes on rat intestinal smooth muscle function

Abstract

Organophosphorous compounds (OP) are highly toxic compounds. Great efforts have been undertaken in the last decades to develop new reactivators of OP-inhibited acetylcholinesterase. So far, a broad-spectrum oxime bearing efficacy against all OP is still missing and alternative approaches are presently under investigation. Previous experiments demonstrated that the bispyridinium non-oxime MB327 was able to improve OP-impaired muscle force in human, rat and guinea pig respiratory muscles and to increase survival in soman, sarin and tabun poisoned guinea pigs. Recent studies indicate that MB327 exhibits a high affinity to muscarinic acetylcholine receptors but up to now, only scarce information is available on the effects of MB327 in isolated organs. Now, the antimuscarinic effect of MB327 was compared to that of established oximes and atropine in a rat jejunum smooth muscle model. MB327 showed a fully reversible smooth muscle relaxing effect at lower concentrations (EC50≈6μM) than all tested oximes. In fact, MB327 exhibited an antimuscarinic smooth muscle relaxing effect at concentrations which were shown to improve OP-impaired skeletal muscle force. Hence, it may be assumed that the antimuscarinic potency of MB327 may contribute to its therapeutic effect in OP poisoning.