Inhibition of the activity of sympathetic preganglionic neurones and neurones activated by visceral afferents, by alpha-methylnoradrenaline and endogenous catecholamines.

The responses of electrophysiologically identified sympathetic preganglionic neurones (SPGN) and neurones activated by visceral afferents (VA) to iontophoretic application of: (1) the intraneuronal metabolites of alpha-methyl-DOPA (alpha-MD): alpha-methylnoradrenaline (alpha-MNA) and alpha-methyldopamine (alpha-MDA); (2) noradrenaline (NA) and adrenaline (Ad); and (3) N-methyl-beta-hydroxy-phenylethylamine (NMPEA), were tested in the upper and lower segments of the thoracic spinal cord of the cat. alpha-Methylnoradrenaline, NA and Ad had an inhibitory action on the majority of spontaneously firing neurones. Inhibition of the activity of preganglionic neurones and neurones activated by visceral afferents induced by alpha-MNA was usually equal to the effect of NA, but in some neurones alpha-MNA was more potent. The transport numbers of both amines are similar. The alpha adrenoceptor antagonists, thymoxamine, piperoxan and yohimbine, antagonized the inhibitory effects of alpha-MNA in spontaneously-active preganglionic neurones and neurones activated by visceral afferents. Piperoxan antagonized also the inhibitory effects of NA. The inhibitory effect of alpha-MDA was weaker and that of NMPEA was much weaker than that of alpha-MNA and NA. The inhibitory effects of alpha-MNA and NA in the cerveau isolé preparation resembled those observed in anaesthetized animals. In reserpinized cats, with catecholamine levels in brain stem and spinal cord reduced by 98-99%, the inhibitory effects of alpha-MNA were preserved. It is postulated that alpha-MNA modulates the activity of preganglionic neurones and that this action, leading to a decrease in sympathetic output and mediated by alpha 1 and alpha 2 adrenoceptors, could be the most important factor in the antihypertensive effect of alpha-MD. The inhibition of the activity of neurones activated by visceral afferents by alpha-MNA indicates that alpha-MD may also attenuate the response of the central nervous system to the input from the heart and other organs.