Trimetoquinol Hydrochloride Hydrate

Isoprenaline, salbutamol, soterenol, and orciprenaline produced dose-dependent decreases in the response of isolated guinea pig trachea to elec. stimulation, the slope of the dose-effect curve and maximum response achieved being similar for each drug.Trimetoquinol produced a plateau effect at the 75% level of inhibition, probably attributable to its β-adrenergic activity.The dose ratios for 50% inhibition were: isoprenaline 1, trimetoquinol 2, soterenol 5, salbutamol 6, and orciprenaline 144.On isolated guinea pig atria preparations, only isoprenaline and orciprenaline had dose-effect curves of similar slope and magnitude on both the rate and force of contractions.Soterenol was a full agonist with respect to rate but a partial agonist with respect to force.Salbutamol and trimethoquinol were partial agonists with respect to both force and rate, although salbutamol had greater agonist activity on rate than did trimetoquinol.The dose ratios with respect to rate (50% maximum) were: isoprenaline 1, soterenol 3.3, orciprenaline 125, and salbutamol 500.A dose ratio for trimetoquinol could not be calculatedThe dose ratios with respect to force were: isoprenaline 1, orciprenaline 63, salbutamol 2500, and soterenol and trimetoquinol <10,000.Salbutamol and trimetoquinol show selectivity for the β-2 type receptors in the trachea, while soterenol has high activity on β-2 type as well as β-1 type (rate) but not β-1 type (force) of the atria, suggesting that β-1 type receptors are not homogeneous.Orciprenaline is not selective and has equal but low activity on both types of receptors.The activities described for these new compounds further substantiate the classification proposed by Lands (1967) for β-receptors in cardiac and bronchial muscle.

Trimetoquinol (TMQ) is a very potent and fast acting bronchodilator in horses with heaves. This study assessed the plasma and urinary concentrations of TMQ in horses with heaves following administration via the intravenous (IV, 0.2 μg/kg) and intra‐tracheal (IT, 2 μg/kg) routes. TMQ was administered to six horses affected with heaves (RAO – Recurrent Airway Obstruction, used interchangeably) by the above routes and plasma and urine samples collected and stored at −20 °C until analyzed. Solid Phase Extraction (SPE) of TMQ was followed by highly sensitive ESI(+)‐LC‐MS‐MS (ElectroSpray Ionization, positive mode – Liquid Chromatography – Mass Spectrometry – Mass Spectrometry); with a Limit of Detection (LOD) estimated at 1 pg/mL. Following IV administration, TMQ plasma levels peaked at 1 min at 707 pg/mL, and at 9 min at 306 pg/mL following IT administration. Our results show that TMQ plasma concentrations decline rapidly following IV administration, which is consistent with the fast onset and short duration of TMQ effect that was observed in our previous studies. On the other hand, IT administration showed a very unique plasma concentration pattern. From a regulatory standpoint, the current available TMQ ELISA kit was also used in an attempt to detect TMQ from the plasma and urine samples. We report that the ELISA kit was unable to detect TMQ from any of the samples generated in these studies.