Differential effects of yohimbine and phenoxybenzamine on norepinephrine metabolites in rat brain

The effects of yohimbine (YOH) and phenoxybenzamine (PB) on the concentrations of norepinephrine (NE) metabolites were compared. In contrast to the large effects of YOH, PB caused only small, nonsignificant increases in brain 3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxyphenylglycol (DHPG). The effects of YOH were unaltered when rats were pretreated with PB. Tyrosine failed to enhance the effect of either YOH or PB except for somewhat augmenting the increase in DHPG induced by YOH. The results rule out the possibility that the small effect of PB on MHPG levels is due to inhibition of NE metabolism, postsynaptic alpha-receptor blockade or to a deficiency in the amino acid precursor tyrosine. Rather, the large effect of YOH is likely due only partly to blockade of presynaptic autoreceptors and partly to another, reserpine-like action. It is also possible that the presynaptic receptors are incompletely blocked by even high doses of PB.