Antinociceptive effects and farmacokinetics in horses treated with different low doses of methadone and detomidine

Abstract

Pain interferes with different organic functions and its prevention and treatment is very important in veterinary medicine. The use of intravenous (IV) opioids in the equine has limitations, mainly due to their adverse effects. Methadone is a µ synthetic agonist, with similar properties as morphine, being also antagonist at the N-methyl-D aspartate (NMDA) receptors. Although its farmacokinetics have been reported in horses, the use of methadone may cause hyperesthesia and ataxia when used alone. Alpha-2-agonists such as detomidine, produce analgesia whereas producing cardiorespiratory depression. The hypothesis of this project is that the association of low doses of detomidine with normal doses of methadone will produce analgesia and small adverse effects. In this context, it will be determined the lower doses of detomidine that would allow the clinical use of methadone. In order to do that, eight adult horses will receive five IV treatments randomly: CONTROL (saline), M (methadone), MDB (methadone with low dose of detomidine), MDM (methadone with medium dose) and MDA (methadone with high dose), with a washout period of one week. The antinociceptive activity will be evaluated by the use of electrical, temperature and pressure stimuli. Heart and respiratory frequencies, sedation levels, gastrointestinal motility, non invasive blood pressure, farmacokinetics and farmacodynamics will be measured. With this project it is expected to determine the minimal doses of alpha-2-agonists in combination with normal doses of methadone that will produce antinociception, with no adverse effects and minimal degree of sedation. In a further phase of the project, and according with the results obtained, the use of constant rate infusions of different combinations of detomidine and methadone will be studied.