Inhibition of Dopamine-B-Hydroxylase in Manic Patients

Treatment Approaches to Mania

“…In other words, because in animals ex cessive psychomotor activity is related to increase in brain DA (Snyder, 1973) and in the light of the findings of Post et al (1973), the increased psychomotor activity may be related to the DA increase in the brain and an increase of speech and elevated mood related to the NE level. Inhibition of dopamine-Bhydroxylase in manic by the administration of fusaric acid, which can selectively deplete NE and not DA, did not produce any significant effect (Sack and Goodwin, 1974). The ambiguous results of this study needs further scrutiny.…”

Double‐blind comparative clinical trial of pimozide and chlorpromazine in mania

“…while generally supporting the catecholamine hypothesis, implicate an increased activity of dopaminergic (DA) rather than noradrenergic (NA) pathways in this condition (Sack & Goodwin (1974), Cookson & Silverstone (1976), Gerner et al (1976)). Correspondingly, central DA overactivity has been proposed as a significant factor in the pathogenesis of manic symptomatology (Goodwin et al (1970), Bunney et a2.…”

A Second Generation Catecholamine Hypothesis

“…In addition, withdrawal of alpha-methyl-para-tyrosine (AMPT), a specific inhibitor of the rate-limiting step in the synthesis of NE and DA, has been associated with the onset of hypomanic episodes. However, fusaric acid, which is a dopamine-beta-hydroxylase inhibitor, was not effective in decreasing manie symptoms (Sack and Goodwin, 1974). This suggests that dopamine, rather than norepinephrine, may be involved in mania since blockade of the synthesis of dopamine and norepinephrine is effective in decreasing mania while blocking synthesis following the formation of dopamine and prior to the formation of norepinephrine is ineffective in decreasing mania.…”