Effects of 4-aminopyridine on the turnover of monoamines in the central nervous system of the rat.

The effects of 4-aminopyridine (4-AP) on the turnovers of 5-hydroxytryptamine, dopamine and noradrenaline in the central nervous system of rats were studied by means of amine disappearance following inhibition of tryptophan or tyrosin hydroxylase. 4-AP (3 mg/kg i.p.) did not change the utilizations of 5-hydroxytryptamine or dopamine but it markedly accelerated that of noradrenaline in the brain and in the spinal cord. This stimulatory effect of 4-AP was completely dependent on nerve impulses since no effect was observed following an acute section of the noradrenaline nerves to the spinal cord. The effect of 4-AP was blocked by the alpha-adrenoreceptor stimulating agent clonidine. Pentylenetetrazole, at a dose producing similar behavioural changes as 4-AP, caused only a slight stimulation of the noradrenaline turnover. 4-AP might enhance the flux of calcium ions into nerve terminals during depolarization, and thus increase the release of noradrenaline, whereas this process might be of less importance in the dopamine and the 5-hydroxytryptamine nerves.