The pharmacological actions of 3,4-dihydroxyphenyl-alpha-methylalanine (alpha-methyldopa), an inhibitor of 5-hydroxytryptophan decarboxylase.
alpha-Methyldopa (3,4-dihydroxyphenyl-alpha-methylalanine) is an inhibitor of 5-hydroxytryptophan decarboxylase which is effective in vitro and in vivo. The inhibition is complex and shows coenzyme reversal. Evidence is presented that it acts by coenzyme inactivation. Its administration to mice reduced brain 5-hydroxytryptamine but had no effect on noradrenaline. After repeated doses, intestinal 5-hydroxytryptamine concentrations were also reduced. Co-ordinated activity was diminished coincidently with the enzyme inhibition and the reduction in brain 5-hydroxytryptamine. Rectal temperatures were reduced and the possibility that this resulted from inactivity is discussed. Treated animals showed miosis and narrowing of the palpebral fissures. A comparison is drawn between the actions of alpha-methyldopa and reserpine. The present results support the idea that the sedative effects of both drugs are due to the fall in brain 5-hydroxytryptamine concentration that they produce.