Sedative and antinociceptive effects of romifidine and xylazine in Thoroughbred mares

The sedative and antinociceptive effects of romifidine (0.1mg/kg) and of xylazine (1.0mg/kg) on Thoroughbred mares were studied. Sedation was evaluated by quantifying spontaneous locomotor activity (SLA) and head height (HH) in animals placed in automated individual behaviour stalls. Antinociception was determined utilizing a heat irradiation lamp recording the latency time for the hoof withdrawal reflex (HWRL) and the latency time for the skin twitch reflex (STRL) in a randomised block design with 10 replicates. Comparison of the sedative effects of romifidine and of xylazine on SLA showed a faster effect for xylazine. Regarding the sedative effect of the substances based on HH, romifidine caused a longer-lasting effect. Romifidine caused an increase in HWRL and STRL, and xylazine, an agent known for its analgesic effect, did not have an antinociceptive effect based on STRL result. The antinociceptive effect of romifidine was more pronounced than the xylazine effect.

Compararam-se os efeitos sedativos e antinociceptivos da romifidina (0,1mg/kg) e da xilazina (1,0mg/kg) em éguas da raça Puro Sangue Inglês. A sedação foi quantificada por meio da atividade locomotora espontânea (ALE) e altura da cabeça (AC) em baias individuais automatizadas para o estudo do comportamento. A antinocicepção foi avaliada utilizando uma lâmpada de irradiação de calor registrando-se a latência para o reflexo de retirada do membro (LRRM) e a latência para o reflexo do frêmito cutâneo (LRFC), em delineamento experimental em blocos ao acaso com 10 repetições. O efeito sedativo sobre a ALE foi de aparecimento mais rápido no grupo exposto à xilazina, ao passo que a ptose da cabeça foi mais prolongada no grupo que recebeu romifidina. A romifidina promoveu aumento da LRRM e LRFC e a xilazina não causou efeito antinociceptivo medido pela LRFC. O efeito antinociceptivo da romifidina foi mais pronunciado que o da xilazina.

Determination of the highest no-effect dose (HNED) and of the elimination pattern for cocaine in horses.

Cocaine is one of the most widespread illegal stimulants utilized by the human population throughout the world. The aim of this study was to establish the highest no-effect dose (HNED) of cocaine on the spontaneous locomotor activity (SLA) of horses in a behavior chamber, and thereby to determine the maximal acceptable threshold of the urinary drug concentration in horses. Twelve English thoroughbred mares received 0.02, 0.03, 0.04, 0.08 or 0.12 mg kg(-1) cocaine i.v. or saline solution (control). It was noted that doses above 0.04 mg kg(-1) induced a significant increase in SLA (P < 0.05, Tukey's test). No significant increase in SLA was seen in the mares that received 0.03 mg kg(-1), but the animals showed important behavioral changes that did not occur after the 0.02 mg kg(-1) dose. It was concluded that the HNED of cocaine for horses in a behavior chamber is 0.02 mg kg(-1). After injection of this dose in five horses, urine samples were collected at predetermined intervals through vesical catheterization. The concentrations of cocaine, norcocaine, benzoylecgonine and ecgonine methyl ester were quantified by liquid chromatography/electrospray ionization tandem mass spectrometry. Cocaine and norcocaine concentrations remained consistently below the level of detection. Benzoylecgonine reached a mean (+/- SEM) maximum concentration of 531.9 +/- 168.7 ng ml(-1) after 4 h, whereas ecgonine methyl ester peaked 2 h after injection at a concentration of 97.2 +/- 26.5 ng ml(-1). The maximum admissible concentration for cocaine and/or metabolites in the urine of horses is difficult to establish unequivocally because of the substantial individual variation in the drug elimination pattern observed in horses, which can be inferred by the large standard error of the means obtained.

Effects of caffeine on locomotor activity of horses: determination of the no-effect threshold.

Caffeine is the legal stimulant consumed most extensively by the human world population and may be found eventually in the urine and/or blood of race horses. The fact that caffeine is in foods led us to determine the highest no-effect dose (HNED) of caffeine on the spontaneous locomotor activity of horses and then to quantify this substance in urine until it disappeared. We built two behavioural stalls equipped with juxtaposed photoelectric sensors that emit infrared beams that divide the stall into nine sectors in a 'tic-tac-toe' fashion. Each time a beam was interrupted by a leg of the horse, a pulse was generated; the pulses were counted at 5-min intervals and stored by a microcomputer. Environmental effects were minimized by installing exhaust fans producing white noise that obscured outside sounds. One-way observation windows prevented the animals from seeing outside. The sensors were turned on 45 min before drug administration (saline control or caffeine). The animals were observed for up to 8 h after i.v. administration of 2.0, 2.5, 3.0 or 5.0 mg caffeine kg(-1). The HNED of caffeine for stimulation of the spontaneous locomotor activity of horses was 2.0 mg kg(-1). The quantification of caffeine in urine and plasma samples was done by gradient HPLC with UV detection. The no-effect threshold should not be greater than 2.0 microg caffeine ml(-1) plasma or 5.0 microg caffeine ml(-1) urine.

Efeitos do amitraz e da xilazina sobre algumas características fisiológicas de cavalos / Effect of amitraz and xylazine on some physiological variables of horses

Avaliaram-se os efeitos das injeçöes intravenosa (iv) de amitraz (0,1mg/kg) e xilazina (1mg/kg), em cavalos, sobre a atividade cardíaca, freqüência respiratória, atividade motora intestinal, temperatura retal, sudorese e freqüência de apreensäo de alimentos. O amitraz causou diminuiçäo significativa da atividade cardíaca, da freqüência respiratória e da movimentaçäo intestinal, mas esses efeitos näo foram täo pronunciados quanto os causados pela xilazina. O amitraz causou, também, relaxamento significativo da musculatura lisa retal, e um aparente aumento da sudorese e da freqüência de cavalos flagrados mastigando feno. A temperatura retal näo foi influenciada pelo amitraz. Os resultados indicam que o amitraz, na dose utilizada, näo causou efeitos colaterais severos em cavalos

Characterization of the antinociceptive and sedative effect of amitraz in horses.

Amitraz, an acaricide used to control ectoparasites in animals has a complex pharmacological activity, including alpha2-adrenergic agonist action. The purpose of this research was to investigate the possible antinociceptive and/or sedative effect of amitraz in horses. The sedative effect of the intravenous (i.v.) injection of dimethylformamide (DMF, 5 mL, control) or amitraz (0.05, 0.10, 0.15 mg/kg), was investigated on the head ptosis test. The participation of alpha2-adrenergic receptors in the sedative effect provoked by amitraz was studied by dosing yohimbine (0.12 mg/kg, i.v.). To measure the antinociception, xylazine hydrochloride (1 mg/kg, i.v., positive control) and the same doses of amitraz and DMF were used. A focused radiant light/heat directed onto the fetlock and withers of a horse were used as a noxious stimulus to measure the hoof withdrawal reflex latency (HWRL) and the skin twitch reflex latency (STRL). The three doses of amitraz used (0.05, 0.10 and 0.15 mg/kg) provoked a dose-dependent relaxation of the cervical muscles. The experiments with amitraz and xylazine on the HWRL showed that after i.v. administration of all doses of amitraz there was a significant increase of HWRL up to 150 min after the injections. Additionally, there was a significant difference between control (DMF) and positive control (xylazine) values up to 30 min after drug injection. On the other hand, the experiments on the STRL show that after administration of amitraz at the dose of 0.15 mg/kg, a significant increase in STRL was observed when compared with the control group. This effect lasted up to 120 min after injection. However, no significant antinociceptive effect was observed with the 0.05 and 0.10 mg/kg doses of amitraz or at the 1.0 mg/kg dose of xylazine.