Effect of Deuterium Substitution in Sympathomimetic Amines on Adrenergic Responses

It was discovered that replacement of the alpha-hydrogens of tyramine and tryptamine by deuterium produces a marked intensification of the blood pressure effects and nictitating membrane contraction normally produced by these amines. The results are interpreted on the basis of kinetic isotope effects at the level of monoamine oxidase and clearly establish the importance of this enzyme in the limitation of responses when tyramine and tryptamine are involved. The observed deuterium isotope effects with alpha,alpha-bisdeuterotyramine (alpha,alpha-D(2)-tyramine) have been reproduced with only one of the optical isomers of monodeuterotyramine. This establishes that the enzyme displays a high degree of optical specificity. The use of l-bisdeuteronorepinephrine revealed that norepinephrine cannot be attacked by the enzyme at the effector cell level.