4-imidazolyl-3-amino-2-butanone (McN-A-1293), a new specific inhibitor of histidine decarboxylase

4-Imidazolyl-3-amino-2-butanone (McN-A-1293) was shown to be an effective inhibitor of fetal rat histidine decarboxylase, but not guinea pig kidney aromatic l-amino acid decarboxylase in vitro. McN-A-1293 was a more potent inhibitor than α-methylhistidine, but less potent than brocresine (NSD-1055) and other aminooxyamines. Kinetic studies using fetal rat histidine decarboxylase indicated the inhibition to be reversible and competitive with histidine. McN-A-1293 in vitro was a less potent inhibitor of diamine oxidase than brocresine and was only a weak inhibitor of imidazole-N-methyltransferase. Administration of McN-A-1293 (200 mg/kg, i.p.) to fed rats resulted in 55 per cent inhibition of gastric histidine decarboxylase, while gastric aromatic l-amino acid decarboxylase was only slightly inhibited (17 per cent). Brocresine (200 mg/kg, i.p.) inhibited both gastric decarboxylases > 60 per cent. Doses of McN-A-1293 as low as 50 mg/kg, i.p., inhibited gastric histidine decarboxylase activity. In fasted rats, McN-A-1293 (200 mg/kg, i.p.) was found to inhibit the elevation in gastric histidine decarboxylase induced by gastrin or insulin. 4-Imidazolyl-3-amino-2-butanone (McN-A-1293) is an effective and specific inhibitor of histidine decarboxylase both in vitro and in vivo and should be a useful agent for studies on the role of histidine decarboxylase in histamine physiology.