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. 1992 Jan;105(1):107–112. doi: 10.1111/j.1476-5381.1992.tb14219.x

Actions of methoctramine, a muscarinic M2 receptor antagonist, on muscarinic and nicotinic cholinoceptors in guinea-pig airways in vivo and in vitro.

N Watson 1, P J Barnes 1, J Maclagan 1
PMCID: PMC1908607  PMID: 1596672

Abstract

1. The effects of the muscarinic M2 receptor antagonist methoctramine, on contractions of airway smooth muscle induced by cholinergic nerve stimulation and by exogenously applied acetylcholine (ACh), have been investigated in vivo and in vitro in guinea-pigs. 2. Stimulation of the preganglionic cervical vagus nerve in anaesthetized guinea-pigs, caused bronchoconstriction and bradycardia which were mimicked by an intravenous dose of ACh. The muscarinic M2 antagonist, methoctramine (7-240 nmol kg-1), inhibited the bradycardia induced by both vagal stimulation and ACh (ED50: 38 +/- 5 and 38 +/- 9 nmol kg-1, respectively). In this dose-range, methoctramine facilitated vagally-induced bronchoconstriction (ED50: 58 +/- 5 nmol kg-1), despite some inhibition of ACh-induced bronchoconstriction (ED50: 81 +/- 11 nmol kg-1). The inhibition of ACh-induced bronchoconstriction and hypotension was dose-dependent, but was not statistically significant until doses of 120 nmol kg-1 and 240 nmol kg-1 respectively. 3. In the guinea-pig isolated, innervated tracheal tube preparation, methoctramine (0.01-1 microM) caused facilitation of contractions induced by both pre- and postganglionic nerve stimulation, whereas contractions induced by exogenously applied ACh were unaffected. Higher concentrations of methoctramine (greater than or equal to 10 microM), reduced responses to both nerve stimulation and exogenous ACh, indicating blockade of post-junctional muscarinic M3 receptors. 4 ACh caused a slow maintained increase in tone of the tracheal tube and at the same time reduced the contractions induced by nerve stimulation. This inhibitory effect of ACh on neuronally mediated responses was antagonized by methoctramine (0.01-1 microM) in a concentration-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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