Effect of drugs on the noradrenaline content of brain and peripheral tissues and its significance.

Large single doses of methoserpidine (12 mg/kg) given to rabbits lowered the noradrenaline content of sympathetic ganglia but not that of brain; no sedation was observed. Cats responded to doses ranging from 12 to 0.5 mg/kg with loss of noradrenaline from ganglia as well as from brain, and were sedated by the drug. The effect in man resembles that in the rabbit. Only within the group of reserpine-like drugs do sedation and loss in hypothalamic noradrenaline run parallel. These effects are therefore not causally related. Guanethidine lowers the noradrenaline content of sympathetic ganglia (cats and rabbits), but this effect does not explain the blocking action of the drug on the adrenergic nerve. Effects on the noradrenaline of the brain are variable and may be caused reflexly rather than by direct central action of guanethidine. Repeated intravenous injections of dimethylphenylpiperazinium iodide for a period of 4 hr did not produce any significant change in the noradrenaline content of ganglia or brain of rabbits. In contrast, dexamphetamine (20 mg/kg) produced a small but significant mean fall in noradrenaline content of the superior cervical ganglia and in that of the brain, but the effects were not seen in every rabbit. Prolonged administration of the mono-amine oxidase inhibitors pheniprazine and phenylhydrazinobutane raised the noradrenaline content of the brain of rabbits but not that of cats, whereas it raised the noradrenaline of the ganglia of cats but not (or rarely) that of rabbits. The question of correlation between a rise in the noradrenaline content of the brain and certain clinical signs is discussed. Finally, a comparison is made in rabbits between the changes produced by drugs in the noradrenaline content of the heart and of the superior cervical ganglion. The changes run parallel and are only occasionally more pronounced in the heart.