Reversal of sympathetic nerve blockade: a comparison of dopa, dopamine, and norepinephrine with their alpha-methylated analogues.

Abstract

Norepinephrine, α-methyl-norepinephrine, dopamine, α-methyl-dopamine, dopa, and α-methyl-dopa were compared over wide and equivalent dose ranges for their ability to reverse the accelerator nerve blockade produced in dogs by reserpine. In addition, the chronotropic and pressor effects of these compounds were compared. (1) NE and M-NE were equipotent and equieffective with respect to their chronotropic and pressor effects. Similarly, these compounds reversed adrenergic nerve blockade to the same degree in 5 out of 6 doses tested. (2) The chronotropic and pressor effects of dopamine and α-methyl-dopamine were similar and the degree of reversal of adrenergic nerve blockade produced by these drugs was the same. (3) Dopa produced significantly greater chronotropic and pressor effects than α-methyl-dopa and also produced significantly greater reversal of adrenergic nerve blockade than α-methyl-dopa, or any other compound tested. (4) NSD 1024 prevented or reduced the reversal of adrenergic nerve blockade by α-methyl-dopa or dopa and also prevented the chronotropic and pressor effects of dopa. NSD 1024 did not prevent any of the effects of dopamine or α-methyldopamine, norepinephrine, or α-methyl-norepinephrine. These observations indicate that M-NE and NE function equally well as sympathetic transmitters in time reserpine-treated dog heart and suggest that α-methyl-dopa is less readily utilized than dopa as a transmitter substrate. In addition, it appears that NSD 1024 was acting as a decarboxylase inhibitor in these experiments.