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1.
α2-Adrenergic receptor agonists are widely used in veterinary medicine as sedative/hypnotic agents. Four pharmacological subtypes of the α2-adrenergic receptor (A, B, C and D) have been identified based primarily on differences in affinity for several drugs. The purpose of this study was to examine the affinities of the sedative agents, xylazine, detomidine and medetomidine at the four α2-adrenergic receptor subtypes. Saturation and inhibition binding curves were performed in membranes of tissues containing only one subtype of a2-adrenergic receptor. The KD for the α2-adrenergic receptor radioligand, [3H]-MK-912, in HT29 cells (α2A-), neonatal rat lung (α2B-), OK cells (α2C-) and PC12 cells transfected with RG20 (α2D-) were 0.38 ± 0.08 n m , 0.70 ± 0.5 n m , 0.07 ± 0.02 n m and 0.87 ± 0.03 n m , respectively. Detomidine and medetomidine had approximately a 100 fold higher affinity for all the α2-adrenergic receptors compared to xylazine but neither agonist displayed selectivity for the α2-adrenergic receptor subtypes. These data suggest that available sedative/hypnotic α2-adrenergic receptor agonists can not discriminate between the four known α2-adrenergic receptor subtypes.  相似文献   

2.
Amitraz, an acaricide used to control ectoparasites in animals has a complex pharmacological activity, including α2-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 α2-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.  相似文献   

3.
The effect of xylazine on the isolated sheep trachea and its possible interactions with the α2-adrenergic antagonist, atipamezole, and the anticholinergic agent, atropine, was studied. The mechanical responses of the tracheal preparations were recorded after exposing each one to cumulatively increasing concentrations of xylazine alone or in the presence of atipamezole or atropine.
Xylazine exerted a concentration-dependent contractile effect, with a threshold concentration of 10--7M while the maximum activity was produced at a concentration of 10--5M (EC50= 2.3 × 10--7). This xylazine-induced contractile effect was inhibited by atipamezole, but not significantly modified by atropine. Thus, it is concluded that α2-adrenoceptors exist in the sheep trachea and it is suggested that α2-adrenoceptor agonists may act on airways in sheep directly through stimulation of peripheral α2-adrenergic receptors and indirectly via central α2-adrenergic receptor activation of parasympathetic tone.  相似文献   

4.
Pupillary response to xylazine (10-300 micrograms/kg, i.v.) norepinephrine (1-30 micrograms/kg. i.v.) and atropine (3-100 micrograms/kg, i.v.) were observed in rats anaesthetized with pentobarbital. Xylazine caused a dose-dependent mydriasis which was antagonized by a selective alpha 2-adrenergic blocking agent, yohimbine (2.5 mg/kg, i.v.). was less effective in antagonizing this effect of xylazine. A selective alpha 1-adrenergic blocking agent, prazosin (2.5 mg/kg, i.v.) was ineffective in reducing the xylazine-induced mydriasis. In contrast, both phentolamine and prazosin blocked the pupillary dilation produced by norepinephrine, while yohimbine was much less effective in antagonizing norepinephrine-induced mydriasis. Atropine also induced a dose-dependent mydriasis which was not affected by yohimbine pretreatment. The present study suggests that the mydriatic effect of xylazine in the rat is mediated by an adrenergic mechanism, possibly by stimulating the alpha 2-adrenergic receptors in the iris and CNS.  相似文献   

5.
Effects of medetomidine on intestinal and colonic motility in the dog   总被引：1，自引：0，他引：1  
The motor responses of the jejunum and colon to stimulation of α2-adrenoceptors by medetomidine and clonidine were investigated in four dogs. In fasting dogs, medetomidine, at a dose rate of 30 μg/kg i.v., disrupted the migrating myoelectric complex (MMC) pattern of the small intestine for about 2 h. Similar, but shorter-lasting effects were also induced by clonidine (30 μg/kg i.v.) on the jejunum. The administration of α2-agonists inhibited colonic motility in fasting dogs, although medetomidine-induced inhibition was preceded by a short period of increased muscle tone. All these effects were reversed by the α2-antagonists atipamezole (0.15 mg/kg i.v.) and yohimbine (0.20 mg/kg i.v.). In fed dogs, medetomidine (30 μg/kg i.v.) induced a strong increase of the tone on the proximal colon, while the activity of the medium and distal colon was completely suppressed. Yohimbine (0.50 mg/kg i.v.) immediately restored the activity of the colon and induced a propagated giant contraction and defaecation by the animal. These data confirm the importance of a2-adrenergic receptors in the control of intestinal and colonic motility in the dog.  相似文献   

6.
Acute pharmacodynamic effects of the α2-adrenoceptor agonists, xylazine and guanfacine, were investigated in nine healthy calves in an open crossover trial. Xylazine (100 μg/kg body weight intravenously (i.v.)) and guanfacine (20 μg/kg body weight i.v.) were equi-effective in lowering heart rate by 25–30% at 5 min. Under these conditions, xylazine induced strong sedation and increased plasma growth hormone levels, indicating central nervous system mediated actions, whereas guanfacine was not sedative and did not induce release of growth hormone. Oxygen consumption was decreased by both drugs, but respiratory exchange ratio decreased only in response to xylazine. However, in response to both drugs, plasma levels of noradrenaline, adrenaline, insulin and non esterified fatty acids decreased similarly and glucose increased comparably. These results demonstrate marked differences in the central nervous system-mediated effects of the two α2-adrenoceptor agonists, whereas peripheral actions are similar.  相似文献   

7.
α2-adrenoceptor agonist drugs can cause respiratory changes leading to a short period of hypoxaemia in sheep. It has been suggested that this is due to transient platelet aggregation and pulmonary microembolism. If platelet aggregation were to follow platelet activation in response to the administration of α2 agonists, plasma thromboxane levels would be expected to rise. This study was carried out to measure plasma thromboxane B2 concentrations before and after the intravenous administration of the α2-agonist drug xylazine at a dose of 0.1 mg/kg. It was found that the plasma thromboxane concentration rose by 320% and, furthermore, the rise was prevented by the prior administration of atipamezole hydrochloride (0.125 mg/kg), an α2-adrenoceptor antagonist.  相似文献   

8.
The effects of intravenous (i.v.), intramuscular (i.m.) and oral administration of lysine-acetylsalicylate (Lys-ASA) on gastro-intestinal motility were investigated in sheep using electromyography. A dose of 20 mg/kg Lys-ASA intravenously reduced the frequency of reticular contractions for 86 ± 18 min, produced abomasal hypomotility and caused a disruption of the cyclical pattern of intestinal motility for at least 120 min. The frequency of reticular contractions measured from 20 to 30 min after Lys-ASA administration was negatively correlated (ß= 0.97; PΔ0.01) to the log of the dose used for doses varying from 10 to 40 mg/kg. Similar effects were observed with intramuscular and oral dose rates of 40 and 80 mg/kg, respectively. Previous i.v. administration of phentolamine (0.1 mg/kg) or tolazoline (2 mg/kg) abolished the effects of Lys-ASA (20 mg/kg) administered intravenously on both reticular contractions and abomaso-intestinal motility.
It was concluded that Lys-ASA administered at therapeutic doses in sheep produced gastro-intestinal motor disturbances and that α-and α2-adrenergic antagonists are able to block them.  相似文献   

9.
A radioreceptor assay technique is described for the measurement of xylazine and medetomidine in sheep plasma. The assay was based on the displacement of tritiated clonidine from a 2-adrenoceptors in a rat brain homogenate by xylazine or medetomidine extracted from plasma. Plasma samples from sheep which had been given xylazine and medetomidine were treated with alumina to remove endogenous catecholamines which would otherwise have bound to α2-- adrenoceptors and interfered with the assay. The drugs were then extracted using chloroform, reconstituted in buffer and used to displace [3H]clonidine. The concentration of α2-agonist was calculated by reference to standard curves. The method had a detection limit of 2.5 ng/mL for xylazine and 0.24 ng/mL for medetomidine. The assay could also be used to detect metabolites capable of binding to α2-receptors.  相似文献   

10.
The effect of medetomidine, a potent and highly selective α2-adrenoceptor agonist, on the motility of the gastric antrum, duodenum, mid-jejunum and ileum was investigated in ten dogs. Its effect on the release of gastrin was also determined. Administration of medetomidine intramuscularly (i.m.) at a dose of 40 μg/kg inhibited the motility of the gastric antrum, duodenum, mid-jejunum and ileum significantly, in comparison to administration of xylazine intramuscularly at a dose of 2.0 mg/kg. The release of gastrin was also significantly decreased in dogs receiving medetomidine. It was found to inhibit the motility in the gastric antrum and duodenum longer than in the mid-jejunum and ileum, presumably by acting specifically on α2-adrenoceptors, likely at the peripheral level. Medetomidine also inhibited the gastric contraction associated with gastrin secretion.  相似文献   

11.
The pharmacokinetic properties of norfloxacin were determined in healthy pigs after single intramuscular (i.m.) and intravenous (i.v.) dosage of 8 mg/kg body weight After i.m. and i.v. administration, the plasma concentration-time graph was characteristic of a two-compartment open model. After single i.m. administration, norfloxacin was absorbed rapidly, with a t max of 1.46 ± 0.06 h. The elimination half-life ( t 1/2β) and the mean residence time of norfloxacin in plasma were 4.99 ± 0.28 and 6.05 ± 0.22 h, respectively, after i.m. administration and 3.65 ± 0.16 and 3.34 ± 0.16 h, respectively, after i.v. administration. Intramuscular bioavailability was found to be 53.7 ± 4.4%. Plasma concentrations greater than 0.2 μg/mL were achieved at 20 min and persisted up to 8 h post-administration. Maximal plasma concentration was 1.11 ± 0.03 μg/mL. Statistically significant differences between the two routes of administration were found for the half-lives of both distribution and elimination phases ( t 1/2α, t 1/2β) and apparent volume of distribution (Vd(area)). In pigs, norfloxacin was mainly converted to desethylenenorfloxacln and oxonorfloxacin. Considerable tissue concentrations of norfloxacin, desethylenenorfloxacin, and oxonorfloxacin were found when norfloxacin was administered intramuscularly (8 mg/kg on 4 consecutive days). The concentration of the parent fluoroquinolone in liver and kidney ranged between 0.015 and 0.017 μg/g on day 12 after the end of dosing.  相似文献   

12.
A high-performance liquid chromatographic method for the determination of the non-steroidal anti-inflammatory drug, oxindanac, in calf plasma is described. Recoveries over the concentration range 0.3 75 to 62.5 μg/ml were 90.2–107.8% with interassay coefficients of variation of 2.1–22.3%. The limit of detection was estimated as 0.10 μg/ml and the limit of quantification calculated to be 0.24 pg/ml in a 1 ml plasma sample. This method was used to establish the pharmacokinetics following intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administration to calves of oxindanac at a dose rate of 2 mg/kg. The elimination t 1/2, was long ( t 1/2 21.2 h after i.v. injection) and absorption was rapid (t1/2B 0.072 h) and complete ( F > 100%) following i.m. administration. Bioavailability was incomplete ( F = 66.6%) following p.o. administration to calves that had been fed on milk, and Wagner-Nelson analysis revealed twoabsorption phases ( t 1/2's 0.20 and 1.9 h). Oxindanac produced long-lasting inhibition of serum TxB2 production, with mean kmax values (% inhibition) of 96.8, 94.1 and 81.3 following i.v., i.m. and p.0. administration, respectively. A single i.v. or i.m. injection of 2 mg/kg oxindanac will probably be active in calves for at least 36–48 h.  相似文献   

13.
The cardiopulmonary effects of the intravenous administration of clonidine (15 μg/kg), ST-91 (30 μg/kg) and diazepam (0.4 mg/kg) were compared in five healthy sheep using a randomized cross-over design, to determine whether the hypoxaemic effects of α2 adrenoceptor agonists are due to sedation, or to peripheral α2 adrenoceptor stimulation. All three drugs significantly lowered arterial oxygen tension (PaO2) levels within 2 min of their administration; however, clonidine and ST-91 produced long lasting and severe hypoxaemia with mean PaO2 levels of ≈40 mm Hg and 50 mm Hg (5.3 kPa and 6.6 kPa), respectively. The fall in PaO2 was considerably less with diazepam (63 mm Hg or 8.4 kPa at 2 min) and by 15 min the values did not differ from placebo treated animals. None of the drugs increased arterial carbon dioxide tension (PaCO2) levels when compared to saline treatment and the acid base variables did not show any significant change. A significant increase was recorded in the packed cell volume of the ST-91 treated group throughout the study. Within 2 min of their administration, all drugs caused a significant increase in mean arterial pressure (MAP) as compared to the placebo treated group. The MAP remained significantly increased for 5 and 60 min after clonidine and ST-91 treatment, respectively. The study shows that ST-91 and clonidine produce a greater degree of hypoxaemia than occurs with diazepam sedation, and that the hypoxaemic effect of α2 adrenoceptor agonists in sheep are mainly mediated by peripheral α2 adrenoceptors.  相似文献   

14.
The ectoparasiticide amitraz stimulates α2,-adrenoceptors to produce side-effects such as bradycardia and hypotension. The actions of amitraz on baroreceptor reflex responses were evaluated in mongrel dogs by occlusion of both carotid arteries for 30-s periods. Incremental doses of amitraz given intravenously showed that doses of 60 μg/kg and above significantly depressed pressor responses to carotid occlusion. By comparison, 2 μg/kg amitraz given by intracisterna magna (i.c.m.) injection significantly depressed both blood pressure and heart rate responses. Pretreatment of dogs with i.c.m. yohimbine (30 μg/kg) prevented the depressant effects of amitraz on the reflex, but prazosin (20 μg/kg), in separate experiments, had no effect.  相似文献   

15.
A comparison of i.v., i.m. and s.c. administration erythromycin base in polyethylene glycol at 15 mg/kg and 30 mg/kg body weight was carried out in beef-type calves of approximately 200 kg body weight. Additional evaluations were carried out with oral administration of erythromycin phosphate and erythromycin stearate. Absorption of erythromycin was very slow by both the i.m. and s.c. routes of administration with a Kab of 0.0135 min-1 and 0.0185 min-1 for i.m. and 0.0032 min-1 and 0.0074 min-1 for s.c. at 15 mg/kg and 30 mg/kg, respectively. The bioavailability (32–42%) and peak serum concentrations were much lower with s.c. than with i.m. (60–65%) administration. The disposition of erythromycin administered i.v. appeared to be representative of dose-dependent kinetics rather than dose-independent first-order kinetics inasmuch as the elimination half-time ( t 1/2B) increased from 174.5 ± 13 min for the 15 mg/kg dosage to 239 ± 10.8 min with 30 mg/kg dosage. An acute apparent cardiovascular effect accompanied i.v. administration of erythromycin at 30 mg/kg dosage but not at 15 mg/kg. Severe diarrhea followed oral administration of either erythromycin phosphate or erythromycin stearate.  相似文献   

16.
Strøm, H. & Krogsgaard Thomsen, M. Effects of non-steroidal anti-inflammatory drugs on canine neutrophil chemotaxis. J. vet. Pharmacol. Therap. 13, 186–191.
Non-steroidal anti-inflammatory drugs exhibit differences in their ability to suppress polymorphonuclear leucocyte (PMN) functions in different species. The present study investigated the in-vitro and ex-vivo effects of phenylbutazone and flunixin on leukotriene-B4-directed migration of canine PMN. Furthermore, in-vitro comparison was made to indomethacin and the 5-lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA). In vitro , flunixin and NDGA were the most potent inhibitors, with IC 50s of 13 and 7 μmol/l, respectively. Phenylbutazone had an IC 50 of 42 μmol/l whereas indomethacin did not achieve 50% inhibition at concentrations less than 100 μmol/l. Ex vivo , flunixin almost completely abolished the LTB4 response at 1h, and still possessed significant inhibitory activity 24 h after a dosage of 1mg/kg i.v. Phenylbutazone was less active ex vivo but did suppress chemotaxis by 23% (P<0.05) at 1h following an i.v. dose of 20mg/kg. It is suggested that part of the anti-inflammatory action of flunixin in dogs may be attributed to inhibition of PMN recruitment.
M. Krogsgaard Thomsen, Department of Pharmacology, Leo Pharmaceutical Products, DK-2750, Ballerup, Denmark.  相似文献   

17.
The effects of jingsongling (JSL) and xylazine on heart rate (HR) and mean arterial pressure (MAP) were studied in five conscious male dogs. An i.v. injection of xylazine (1 mg/kg) caused a bradycardia, an initial hypertension, and a subsequent hypotension. An i.v. injection of JSL (1 mg/kg) caused a bradycardia and a 20-min hypertension without a subsequent hypotension. Atropine sulfate (45 micrograms/kg, i.v.) increased HR for 30 min without changing MAP, and antagonized JSL-induced bradycardia for at least 60 min. There was a subsequent rebound bradycardia. Atropine sulfate potentiated JSL-induced hypertension in both magnitude and duration. Yohimbine (0.1 mg/kg, i.v.), an alpha 2-adrenoceptor antagonist, increased HR and MAP for 110 and 70 min, respectively. Yohimbine not only failed to potentiate but even reversed the pressor effect of JSL in a dose-dependent manner. Yohimbine also caused a dose-dependent reversal of JSL-induced bradycardia. Tolazoline (5 mg/kg, i.v.), a nonselective alpha-adrenoceptor antagonist, increased MAP for 20 min without changing HR. Tolazoline also reversed JSL-induced hypertension and bradycardia. Prazosin (1 mg/kg), an alpha 1-adrenoceptor antagonist, decreased MAP and increased HR for at least 110 min. Prazosin reversed JSL-induced hypertension but failed to affect JSL-induced bradycardia. These results indicated that: (1) JSL-induced bradycardia and hypertension are mediated by alpha 2-adrenoceptors; (2) yohimbine and tolazoline may be useful in antagonizing these untoward reactions associated with JSL administration, whereas prazosin and atropine were not found to be beneficial in this regard.  相似文献   

18.
The purpose of this study was to investigate the effects of some a and β sympathomimetic and sympatholytic drugs on respiratory impedance in healthy conscious calves. Ten Friesian calves were investigated in this study. The forced oscillation technique was used to measure the resistance ( R rs) and the reactance ( X rs) of the respiratory system at frequencies ranging from 4 to 26 Hz. Isoprenaline (1 μg/kg i.v.), propranolol (3 μg/kg i.v.), noradrenaline (2 μg/kg i.v.), xylazine (20 μg/kg i.v.) and yohimbine (0.25 mg/kg i.v.) were administered. Isoprenaline induced a significant decrease of R rs. An increase of R rs after administration of propranolol was observed but without any change of the frequency dependence of R rs. A small increase in the resonant frequency was also recorded. A decrease of R rs was recorded after yohimbine injection. Noradrenaline and xylazine administration increased the resistances and the resonant frequency and induced a negative frequency dependence of R rs. These results suggest that (1) the major effects of β adrenergic drugs are on the central airways, (2) the a adrenergic system may play a role on the regulation of bronchomotor tone in calves, (3) the effects of a adrenergic drugs are on both central and peripheral airways and (4) the forced oscillation technique allows the differentiation of calibre changes occurring in small and large airways.  相似文献   

19.
Plasma pharmacokinetics and urine concentrations of meropenem in ewes   总被引：1，自引：0，他引：1  
The pharmacokinetics of meropenem was studied in five ewes after single i.v. and i.m. dose of 20 mg/kg bw. Meropenem concentrations in plasma and urine were determined using microbiological assay method. A two-compartment open model was best described the decrease of meropenem concentration in plasma after an i.v. injection. The drug was rapidly eliminated with a half-life of elimination ( t 1/2 β ) of 0.39 ± 0.30 h. Meropenem showed a small steady-state volume of distribution [ V d(ss)] 0.055 ± 0.09 L/kg. Following i.m. injection, meropenem was rapidly absorbed with a t 1/2ab of 0.25 ± 0.04 h. The peak plasma concentration ( C max) was 48.79 ± 8.83  μ g/mL was attained after 0.57 ± 0.13 h ( t max). The elimination half-life ( t 1/2el) of meropenem was 0.71 ± 0.12 h and the mean residence time ( MRT ) was 1.38 ± 0.26 h. The systemic bioavailability (F) after i.m. injection was 112.67 ± 10.13%. In vitro protein-binding percentage of meropenem in ewe's plasma was 42.80%. The mean urinary recoveries of meropenem over 24 h were 83% and 91% of the administered dose after i.v. and i.m. injections respectively. Thus, meropenem is likely to be efficacious in the eradication of many urinary tract pathogens in sheep.  相似文献   

20.
This study was carried out to determine whether yohimbine antagonizes the retrograde flow of spermatozoa into the urinary bladder of dogs caused by xylazine. Adult dogs were assigned to one of four groups of six dogs each and treated as follows: saline control, xylazine (2.2 mg/kg, i.m.), yohimbine (0.2 mg/kg, im.), yohimbine/xylazine (yohimbine, 0.2 mg/kg, i.m., followed 10 min later by xylazine. 2.2 mg/kg, i.m.). Pre- and post-treatment urine were collected by cystocentesis from all dogs. The mean (± SD) adjusted total number of spermatozoa in the post-treatment urine of xylazine-treated dogs (141.02 ± 136.75 × 106) was 15 times higher ( P < 0.05) than the number in the post-treatment urine of control dogs (9.16 ± 20.26 × 106), 1763 times higher ( P < 0.05) than the number in the urine of yohimbine-treated dogs (0.08 ± 0.20 × 106), and 56 times higher ( P < 0.05) than the total number in the post-treatment urine of yohimbine/xylazine-treated dogs (2.54 ± 4.54 × 106). These results confirm that xylazine induces a significant ( P = 0.007) displacement of spermatozoa into the urinary bladder of dogs and demonstrate that pre-treatment with yohimbine prevents this effect.  相似文献   

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