Abstract
The decarboxylase-inhibiting effects of several drugs were studied in vitro. α-Methyl-dopa was slightly more potent than α-ethyl-dopa but less potent than NSD-1034, NSD-1039 or NSD- 1055 as a decarboxylase inhibitor. The decarboxylation of α-ethyl-dopa to α-ethyl-dopamine was not detected in a system which formed easily measurable quantities of α-methyl-dopamine from α-methyl-dopa. The decarboxylation of α-methyl-dopa was completely inhibited by low concentrations of NSD-1034, NSD-1039 or NSD-1055.
The same drugs were examined for in vivo effects on decarboxylase activity and norepinephrine levels in the brain and heart of the guinea pig. Inhibition of decarboxylase by α-methyl-dopa and by α-ethyl-dopa required large doses and was of short duration. NSD- 1039 and NSD-1055 were much more potent decarboxylase inhibitors; their effects diminished only slightly in 24 hours. Neither NSD- 1055 nor α-ethyl-dopa depleted norepinephrine from tissue. Norepinephrine depletion by α- methyl-dopa was prevented by pretreatment with suitable doses of NSD-1055. α-Ethyl-dopamine was found to be effective in depleting norepinephrine levels in the heart.
These findings support the belief that decarboxylase inhibition does not decrease tissue norepinephrine levels and that α-substituted amino acids are dependent upon decarboxylation to the corresponding amines for their pharmacologic and norepinephrine-depleting effects.
Footnotes
- Accepted June 17, 1964.
- The Williams & Wilkins Comapny
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|