Alpha-methyltyrosine

QUESTION Do you get bigger effects on some of the behavioral parameters after the amphetamine treatments if you pretreat the animals with a low dose of alpha methyltyrosine during that period, during the postamphetamine period In the old days, when we had a partial lesion, we gave a low dose of AMFT, and it would reexpose the lesion. Have you tried that ... 

Commins, D.L., and Seiden, L.S. Alpha-methyltyrosine blocks methylamphetamine-induced degeneration in the rat somatosensory cortex. Brain Res 365 15-20, 1986. 

QUESTION How do you imagine that both a receptor antagonist and an uptake inhibitor would block the effects It would seem that if dopamine is involved, it would either be acting on a membrane receptor or inside, but not both. I would also like to ask a more specific question. You showed that the alpha MT protected effect could be reversed by dopa. And I think you imagined that that was because of dopamine formation. But have you tried dopamine agonists to see if they would antagonize either the protective effect of alpha methyltyrosine or, particularly, the protective effect of the dopamine antagonists to try to verily that those protective effects really have to do with blockade of a dopamine receptor as opposed to some other possibility ... 

Green KN, Larsson SK, Beevers DG, Bevan PG, Hayes B. Alpha-methyltyrosine in the management of phaeochromo-cytoma. Thorax 1982 37(8) 632-3. 

Ram CV, Meese R, HiU SC. Failure of alpha-methyltyrosine to prevent hypertensive crisis in pheochromocytoma. Arch Intern Med 1985 145(11) 2114-15. 

During the past year several studies have appeared in the literature bearing on the relationship of 5-HT and/or its precursor to depression. Shopsin et al., in two studies, were able to show that the positive therapeutic response of depressed patients to imipramine 25 or tranylcyromine 28 could be reversed by co-administration of the tryptophan hydroxylase inhibitor PCPA (p-chlorophenylalanine). These same investigators could not show any effect of alpha-methyltyrosine, a tyrosine hydroxylase inhibitor, on the positive clinical response to imipramine. 25 These data seem to indicate that serotonin, rather than catecholamines, is involved in depression. 

Tyrosine is converted to dopa by the rate-limiting enzyme, tyrosine hydroxylase, which reqnires tetrahydro-biopterin and is inhibited by alpha-methyltyrosine. Dopa is decarboxylated to dopamine by L-aromatic amino acid decarboxylase, which reqnires pyridoxal phosphate (vitamin Bg) as a coenzyme. Carbidopa, which is used with l-dopa in the treatment of parkinsonism, inhibits this enzyme (see Figure 37). Dopamine is converted to norepinephrine by dopamine beta-hydroxylase, which requires ascorbic acid (vitamin C), and is inhibited by diethyldithiocarbamate. Norepinephrine is converted to epinephrine by phenyletha-nolamineN-melhyltransferase (PNMT), requiring S-adenosyl-methionine. The activity of PNMT is stimulated by corticosteroids. 

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