Some factors affecting the neuron blocking action of guanethidine, xylocholine, bretylium and debrisoquin.

The uptake of guanethidine (3.3×10-5 M), debrisoquin (8.4×10-4 M), bretyliun (5.0 10-4 M) and xylocholine (1.0×10-3 M) by adrenergic neuron was studied indirectly by testing the ability of noradrenaline (NA) regarding low temp. or sodium deprivation to prevent or reverse adrenergic neuron blocking action in the indirectly stimulated guinea-pig hypogastric nerve vas deferens preparations. NA (3.0×10-3 M) completely prevented the neuron blocking action of all the four blockers but re versed only that of bretylium. Exposure of preparations to a low temp. (0°C) pre vented the neuron blocking action of all the four blockers but did not reverse that of anv one blocker. The adrenergic neuron blocking action of guanethidine was partially prevented but was not reversed by sodium-deprivation. Sodium-depriva tion neither prevented nor reversed the neuron blocking action of the other three blockers. It is concluded that guanethidine shares the uptake mechanism of NA for transport across the neuron while debrisoquin, bretylium and xylocholine appear to be transported differently. The uptake of noradrenaline (NA) by the adrenergic neuron is energy dependent (1, 2, 3) and sodium dependent (4, 5, 6, 7, 8, 9). Guanethidine utilises this NA uptake me chanism for transport across the membrane of neurons (10, 11) and of human platelets (12) which can serve as convenient model for the neuron (13). Support for this common transport mechanism for NA and guanethidine is derived from observations of the ability of NA to block the uptake of guanethidine, and the failure of uptake of guanethidine in sodium-deficient medium and under conditions of reduced energy supply as at low temp. (12). Gulati and Jaykar (14) showed that in the Finkleman preparation (15), the neuron blocking action of guanethidine was prevented by NA, sodium-deprivation and at low temp. and concluded that guanethidine shares the uptake mechanism for NA. Since the neuron blocking action of a neuron blocker is consequential upon the uptake by the neuron, the prevention of neuron block by various procedures and drugs affecting uptake of NA should provide information about the uptake of a neuron blocker. Thus the present cotn munication is concerned with the investigation of the influence of NA, low temp. and so dium-deprivation in modifying the adrenergic neuron blocking action on Hukovic pre paration (16) Of guanethidine, xylocholine, bretylitun and debrisoquin. In addition the mechanisms ol' the utitake Of these neuron bloekers into the adrenergic neurons are dis