Hordenine: pharmacology, pharmacokinetics and behavioural effects in the horse

Abstract

Summary Hordenine is an alkaloid occurring naturally in grains, sprouting barley, and certain grasses. It is occasionally found in post race urine samples, and therefore we investigated its pharmacological actions in the horse. Hordenine (2.0 mg/kg bodyweight [bwt]) was administered by rapid intravenous (iv) injection to 10 horses. Typically, dosed horses showed a flehmen response and defecated within 60 secs. All horses showed substantial respiratory distress. Respiratory rates increased about 250 per cent and heart rates were approximately double that of resting values. All animals broke out in a sweat shortly after iv injection, but basal body temperature was not affected. These effects were transient, and the animals appeared normal within 30 mins of dosing. Treated horses were tested in a variable interval responding apparatus 30 mins after dosing and no residual stimulation or depressant effects of hordenine were apparent. Animals dosed orally with 2.0 mg/kg bwt of hordenine showed no changes in heart rate, respiratory rate, basal body temperature or behaviour. After iv injection of hordenine, (2.0 mg/kg bwt) plasma reached a maximum value of about 1.0 μg/ml, and declined thereafter in a biexponential fashion. Kinetics of plasma concentration satisfied the concept of a two compartment open system, with an α‐phase half‐life of about 3 mins, and a ß‐phase half‐life of about 35 mins. Total urinary concentrations of hordenine (free and conjugated) peaked at about 400 μg/ml, and then declined exponentially to background levels by 24 h after dosing. Oral administration of hordenine (2.0 mg/kg bwt) showed peak plasma levels of about 0.15 μg/ml 1 h after dosing, followed by a slow multi‐exponential decline in blood levels of the drug. Total urinary concentrations of hordenine (free and conjugated) peaked at about 200 μg/ml, remained at this level for about 8 h, and then declined to background levels. Plasma levels of hordenine were reflected by a kinetic model which assumed very slow absorption of hordenine from the gastrointestinal tract and no effect on behaviour, heart rate or respiratory rate were noted after oral administration. Because of the low plasma levels, it would appear to be particularly difficult to obtain a pharmacological effect of hordenine after oral administration.

Label-free target identification using in-gel fluorescence difference via thermal stability shift

“…17 Hordenine has several bioactivities such as the stimulation of gastrin release in rats, 18 the inhibition of norepinephrine uptake in isolated vasa deferentia, 19 and the increases in respiratory and heart rates when intravenously injected into horses. 20 From screening of small-molecule libraries to identify compounds affecting in vitro protein translation, hordenine was found to increase the translation of the luciferase reporter gene (Fig. 4b).…”

At a Supra-Physiological Concentration, Human Sexual Hormones Act as Quorum-Sensing Inhibitors

“…Hordenin (CAS# 3595-05-9) is a natural alkaloid of the phenethylamine class exhibiting a widespread occurrence in plants (ornamentals, fruits and vegetables), including those that are used for human and animal consumption [22]–[23]. Following injection, hordenine stimulates the release of norepinephrine in mammals hence acting indirectly as an adrenergic drug [24]–[25]. In the literature, alkaloid compounds have been less frequently reported as acting as QSI than aromatic or polyaromatic compounds [1].…”

Alkaloids of the Cactaceae — The Classics

“…The intravenous and oral administration of 2.0 mg/kg hordenine was studied in horses. Although the intravenous dose caused a short-lived variety of effects including respiratory distress, none of these effects were seen after oral administration, apparently because of the alkaloid's poor absorption, attaining a peak plasma value of 0.15 g/mL one hour after dosing [36,37]. However, a significant hypertensive effect was observed in rats after oral administration of 1.0 mg/kg of hordenine and of several of its glycosides [38].…”