Comparison of the effects of methoxamine with those of noradrenaline and phenylephrine on single cerebral cortical neurones.

1 The technique of microelectrophoresis was used to compare the actions of methoxamine, noradrenaline and phenylephrine on single neurones in the somatosensory cerebral cortex of the rat.2 Methoxamine evoked only excitatory responses on cortical neurones. The methoxamine-sensitive cells were also excited by phenylephrine; cells excited by methoxamine could either be excited or depressed by noradrenaline.3 Methoxamine appeared to be less potent than either noradrenaline or phenylephrine in evoking excitatory responses.4 Responses to methoxamine had a slower time course than responses to either noradrenaline or phenylephrine, both the latencies to onset and the recovery times being longer for responses to methoxamine than for responses to noradrenaline or phenylephrine.5 When the absolute mobilities of methoxamine, noradrenaline and phenylephrine were compared using an in vitro method, no significant differences were found between the mobilities of the three ionic species, suggesting that the three drugs have similar transport numbers. Thus the differences in potency between methoxamine and the other two drugs, and the difference between the time courses of responses to methoxamine and the other two drugs, are presumably of biological origin.6 The alpha-adrenoceptor antagonist, phenoxybenzamine, antagonized equally excitatory responses to methoxamine and noradrenaline, and responses to methoxamine and phenylephrine, without affecting responses to acetylcholine.7 When responses to methoxamine and noradrenaline and responses to methoxamine and acetylcholine were summated on the same cells, the net responses were smaller than those expected on the basis of additive effects; the deviation from additivity was greater in the case of the summation of responses to methoxamine and noradrenaline than in the case of summation of responses to methoxamine and acetylcholine. This observation is consistent with the hypothesis that the interaction between methoxamine and noradrenaline follows the model of competitive dualism, whereas the interaction between methoxamine and acetylcholine follows the model of functional synergism.8 The results suggest that methoxamine may act as a partial agonist at excitatory alpha-adrenoceptors on cerebral cortical neurones.