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1 The metabolism and disposition in blood and tissues of exogenous ["4C]-histamine was examined in cats.2 The principal metabolites in blood of histamine instilled into the small intestine (directly or by transfer from the stomach) and colon were imidazoleacetic acid and t-methylimidazoleacetic acid, being present in approximately equal amounts although in individual cats one or other acid could predominate. Only small amounts of histamine entered the circulation although in two of four cats given the largest dose (82 1imol/kg) large amounts were recovered. The amount of "4C radioactivity absorbed varied directly with the dose instilled. The chief metabolite in kidney and urine, whether histamine was instilled into the intestine or infused parenterally, was t-methylimidazoleacetic acid. Histamine was not absorbed from the stomach and its metabolism there was negligible. 3 In contrast, when histamine was infused into blood leaving the intestine (portal vein) the main metabolite in blood and tissues was t-methylimidazoleacetic acid being found in approximately 5-fold the concentration of imidazoleacetic acid. The small amount of histamine which eluded inactivation/uptake by liver, lungs, heart during the infusion was halved on circulation through the intestine. When histamine was infused into blood supplying the intestine, (cranial mesenteric artery) t-methylimidazoleacetic acid while still the major metabolite in blood was now only 1.4 times the concentration of imidazoleacetic acid. Additionally, the blood concentration of histamine during the infusion exceeded that of the metabolites. 4 t-Methylimidazoleacetic acid was also the principal metabolite in blood and tissues following histamine infusion into a cannula carrying a replacement venous blood supply to the liver of abdominally eviscerated cats. Imidazoleacetic acid and t-methylhistamine were present in equal concentrations and in one-quarter to one-third that of the methylated acid. The latter was also the principal metabolite following intra-arterial histamine infusion to abdominally eviscerated cats without a hepatic blood supply, although initially t-methylhistamine predominated: a large peak of histamine was present during the infusion period. When additionally the renal vessels were ligated, t-methylhistamine predominated throughout the experiment. 5 In conclusion, intraduodenally instilled histamine was metabolized equally by diamine oxidase and imidazole N-methyltransferase (followed by deamination by monoamine oxidase). In contrast, imidazole N-methyltransferase was the principal inactivator of parenterally infused histamine, deamination of t-methylhistamine by monoamine oxidase becoming progressively less efficient with the cumulative exclusion of the intestines, liver and kidney from the circulation.

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[14C]‐β‐phenethylamine ([14C]‐PEA) was instilled intragastrically, intraduodenally (i.d.) or infused into the portal vein or femoral artery of cats, anaesthetized with chloralose, to investigate its distribution in the body. [14C]‐PEA and phenylacetic acid (PAA) accounted for approximately 85% of radioactivity recovered in blood from control cats or those pretreated with deprenyl or mebanazine. Progressively greater portal venous (PV), cranial mesenteric arterial (CMA) and PV‐CMA concentrations of PEA and PAA were observed with increase in amount of PEA instilled intraduodenally (i.d.); PAA predominated over PEA, more so in CMA than PV blood. Radioactivity was not recovered from blood following intragastric instillation of PEA. When histamine 1.7 μmol kg−1, i.d., was combined with PEA 1.7 μmol kg−1, i.d., or tyramine 8.5 μmol kg−1, i.d., was combined with PEA 8.5 μmol kg−1, i.d., PV‐CMA values for PEA were significantly augmented. Arterial concentrations of PEA were increased 3.5 to 5 fold compared to controls by pretreatment with mebanazine or deprenyl plus clorgyline; arterial concentrations of PAA were reduced. PEA blood concentrations were not significantly altered by clorgyline or deprenyl pretreatment. Infusion of PEA 680, 1020 or 1360 nmol kg−1 min−1 for 20 min into the portal vein raised blood pressure 60 to 100 mmHg (at a PEA concentration of ca, 2 nmol ml−1) but lacked effect on the nictitating membrane despite peak arterial PEA concentrations of 20 nmol ml−1; in cats pretreated with mebanazine or clorgyline plus deprenyl, half‐maximum contraction of the nictitating membrane occurred with arterial PEA concentrations of 4.8 to 9 nmol ml−1. In cats pretreated with mebanazine or deprenyl plus clorgyline, half maximum contraction of the nictitating membrane was elicited also by intraduodenal PEA 8.5 μmol kg−1 at arterial PEA concentrations of ca. 2 nmol ml−1, despite lack of effect of PEA 17 μmol kg−1, i.d., in control cats with a peak arterial PEA concentration of 1.8 nmol ml−1. [14C]‐PEA and PAA were recovered from liver, kidney, distal small intestine, lung, arterial vessel walls, skeletal muscle, brain, foetus and amniotic liquor, after PEA instilled i.d., overall concentration of PEA exceeding that of PAA except in the kidney. The combined amount of PEA and PAA in kidney was 7 to 20 fold that in other tissues. PEA content of tissues was significantly elevated and that of PAA diminished by pretreatment with deprenyl plus clorgyline, and to a lesser extent after mebanazine.