[¹⁴C]‐β‐phenethylamine, its distribution after administration by various routes to cats, and the effects of monoamine oxidase inhibitors

Abstract

[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.

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“…The differences between the results ofthe present investigation and those described previously might be due to differences in doses employed and routes of PEA administration. Recent studies indicate dose-dependent non-linear pharmacokinetics (Shannon et al, 1982) and route of administration-dependent kinetics of elimination for PEA (Garcha et al, 1985).…”