Liberation of α-methyldopamine as a “false” sympathetic transmitter after pretreatment of cats with α-methyldopa and disulfiram

Summary Pretreatment of cats with -methyldopa (3×200 mg/kg i.p. given over a period of 28 hrs) and simultaneous inhibition of dopamine -hydroxylase by disulfiram (4×400 mg/kg p.o. given over a period of 44 hrs) diminished the norepinephrine content of the heart to 31% and of the spleen to 15% of control levels. The missing norepinephrine was only partially replaced by -methyldopamine and the total catecholamine content of spleen and heart amounted to 51 and 70% respectively of untreated controls. In spinal cats the response of the nictitating membrane to sympathetic nerve stimulation was markedly diminished, whereas the effect of intravenously injected norepinephrine on blood pressure and nictitating membrane was considerably potentiated. In the isolated perfused spleen the contractile response to sympathetic nerve stimulation was also diminished and the pressor activity (expressed in terms of norepinephrine) of the venous effluent was reduced to 40% at a stimulating rate of 6/sec and to 39% at 10/sec. Together with the diminished amounts of norepinephrine -methyldopamine appeared as a false sympathetic transmitter in the perfusion fluid. The two amines were liberated by sympathetic nerve stimulation in the same proportions in which they were stored in splenic tissue.From this and previous studies it becomes apparent that several aspects must be considered in correlating biochemical and functional findings: amounts of normal transmitter in tissues versus amounts liberated by sympathetic nerve stimulation, quantitative aspect of replacement of the physiological by the false transmitter in tissues and in the output from stimulated nerves, potency of the false transmitter at adrenergic receptors and its possible interference with transmitter inactivation.Preliminary results of this report have been communicated to the German Pharmacological Society in Mainz at the Spring meeting 1966.