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 mgkg bodyweight [bwt]) was administered by rapid intravenous (iv) injection to 10 horses. Typically, dosed horses showed a tlehmen 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. Tkeated 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 mgkg bwt of hordenine showed no changes in heart rate, respiratory rate, basal body temperature or behaviour. After iv injection of hordenine, (2.0 mgkg bwt) plasma reached a maximum value of about 1.0 pglml, and declined thereafter in a biexponential fashion. Kinetics of plasma concentration satisfied the concept of a two compartment open system, with an a-phase half-life of about 3 mins, and a P-phase half-life of about 35 mins. Total urinary concentrations of hordenine (free and conjugated) peaked at about 400 pg/ml, and then declined exponentially to background levels by 24 h after dosing. Oral administration of hordenine (2.0 mgkg bwt) showed peak plasma levels of about 0.15 pg/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 pg/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.
This study was supported by a grant from the Kentucky Equine Drug Research Council and the Kentucky State Racing and Hamess Racing Commissions.
Frank, M.; Weckman, T. J.; Wood, T.; Woods, W. E.; Tai, Chen L.; Chang, Shih-Ling; Ewing, A.; Blake, J. W.; and Tobin, Thomas, "Hordenine : pharmacology, pharmacokinetics and behavioural effects in the horse" (1991). Maxwell H. Gluck Equine Research Center Faculty Publications. 91.