The Treatment with Dextromethorphan of Heroin Addicts

Abstract

In our previous studies, L-aspartic acid (L-ASP) was found to antagonize the inhibitory effects of acute and chronic morphine (M) administration on brain L-asparaginase activity, the developement of physical dependence on M and the manifestation of M abstinence syndrome (19, 21, 24, 26). As a result of these experimental data, we hypothesized that the mechanisms underlying the development of physical dependence on opiates and the abstinence syndrome upon withdrawal from opiates are the inhibition by opiates of the brain L-asparaginase and glutaminase activities, and the disequilibrium due to the inhibitory effect of opiates between L-asparaginase and asparagine synthetase +L-glutaminase and glutamine synthetase (14, 20, 40). As a consequence, the inhibition of the brain L-asparaginase and glutaminase activities, and the subsequent relative hyperactivities of asparagine and synthetases result in less production of the excitatory neurotransmitter amino acids (EAAs), namely ASP and L-glutamic acid (L-GLU), and prompt adaptation of the organism to this newly created state. The similar effects of another L-asparaginase inhibitor D-ASP (30) to those of M (15, 17), the intensification or attenuation by D-ASP administered at the beginning of the M physical dependence development or just before the naloxone precipitated abstinence syndrome (22), and the successful treatment with L-ASP (14, 40) of opiate addicted people have been considered to be supporting evidence for the hypothesis.