Actions of noradrenaline, other sympathomimetic amines and antagonists on neurones in the brain stem of the cat.

1. The effects of (-)-noradrenaline ((-)-NA) and related compounds on brain stem neurones in decerebrate unanaesthetized cats have been investigated using the technique of iontophoretic application from micropipettes.2. Four types of response to (-)-NA have been described. These were short lasting inhibition, long lasting inhibition, excitation, and a biphasic response consisting of short lasting inhibition followed by excitation. A variable amount of desensitization of the excitatory response, but not of inhibitory responses, was observed.3. Experiments in which small currents were used to pass (-)-NA from pipettes with smaller tips did not lead to any appreciable change in the proportions of neurones excited or inhibited.4. A variety of sympathomimetic agonists was tested. Short lasting inhibition was less sensitive than excitation to changes in molecular structure. Long lasting inhibition was more sensitive to molecular change and was not mimicked by some of the agonists which mimicked short lasting inhibition.5. Although agonists without one ring hydroxyl had weaker effects than those with both, compounds in which both ring hydroxyl groups were absent (beta-hydroxyphenylethylamine, ephedrine and amphetamine) mimicked excitation strongly. It is possible that the compounds without both ring hydroxyl groups had some effect other than simple agonistic activity.6. A dissociation was observed between responses to dopamine and (-)-NA. p-Tyramine mimicked dopamine, rather than (-)-NA.7. Neither the alpha-agonist, phenylephrine nor the beta-agonist, isoprenaline mimicked neuronal responses to (-)-NA. The alpha-antagonists phentolamine and phenoxybenzamine and the beta-antagonists dichloroisoprenaline, propranolol and D(-)-INPEA and combinations of propranolol with phentolamine or phenoxybenzamine were ineffective in blocking either excitation or inhibition. Thus, the central receptors appear to be different from peripheral alpha- and beta-receptors.8. The most effective antagonist of excitation was (-)-alpha-methylnoradrenaline. Metaraminol and dihydroergotamine also had some antagonistic activity. None of the compounds tested blocked inhibition. The effects of (-)-alpha-methylnoradrenaline have been discussed in relation to the hypotensive action of alpha-methyldopa.