Effects Of Medetomidine Research Articles

Effects of medetomidine, l–methadone, and their combination on arterial blood gases in dogs

ObjectiveTo investigate the influence of l–methadone on medetomidine–induced changes in arterial blood gases and clinical sedation in dogs. Study designProspective experimental cross–over study (Latin square design). AnimalsFive 1–year–old purpose bred laboratory beagle dogs of both sexes. MethodsEach dog was treated three times: medetomidine (20 μg kg−1 IV), l–methadone (0.1 mg kg−1 IV) and their combination. Arterial blood was collected for blood gas analysis. Heart and respiratory rates were recorded, and clinical sedation and reaction to a painful stimulus were scored before drug administration and at various time points for 30 minutes thereafter. ResultsArterial partial pressure of oxygen decreased slightly after medetomidine administration and further after medetomidine/l–methadone administration (range 55.2–86.7 mmHg, 7.4–11.6 kPa, at 5 minutes). A slight increase was detected in arterial partial pressure of carbon dioxide after administration of l–methadone and medetomidine/l–methadone (42.6 ± 2.9 and 44.7 ± 2.4 mmHg, 5.7 ± 0.4 and 6.0 ± 0.3 kPa, 30 minutes after drug administration, respectively). Arterial pH decreased slightly after administration of l–methadone and medetomidine/l–methadone. Heart and respiratory rates decreased after administration of medetomidine and medetomidine/l–methadone, and no differences were detected between the two treatments. Most dogs panted after administration of l–methadone and there was slight sedation. Medetomidine induced moderate or deep sedation, and all dogs were deeply sedated after administration of medetomidine/l–methadone. Reaction to a noxious stimulus was strong or moderate after administration of methadone, moderate or absent after administration of medetomidine, and absent after administration of medetomidine/l–methadone. Conclusions and clinical relevanceAt the doses used in this study, l–methadone potentiated the sedative and analgesic effects and the decrease in arterial oxygenation induced by medetomidine in dogs, which limits the clinical use of this combination.

The effect of the novel alpha–2–adrenoceptor agonist naphthylmedetomidine on pulse rate, arterial blood pressure and sedation in rabbits

ObjectiveThe aim of this study was to investigate the effect of a novel alpha–2–adrenoceptor (α2–AR) agonist, naphthylmedetomidine, on cardiorespiratory function and sedation in rabbits in comparison with medetomidine. Study designProspective, randomized, experimental trial. AnimalsForty–two chinchilla rabbits of both sexes, weighing 2.5–4.5 kg. MethodsThe rabbits received 350 μg kg−1 naphthylmedetomidine (n = 21) or medetomidine (n = 21) intramuscularly according to a randomization scheme. Arterial blood pressure (AP), oxygen saturation of haemoglobin (SpO2), pulse rate (PR) and righting reflex were monitored for 20 minutes after injection. ResultsBoth drugs significantly decreased PR. The effect of medetomidine was significantly greater than that of naphthylmedetomidine and was evident within 1 minute. The decrease in PR after naphthylmedetomidine administration first appeared after 4 minutes. Medetomidine decreased the SpO2 after 3 minutes but there was no effect after naphthylmedetomidine. Medetomidine decreased the mean, systolic and diastolic AP within 5 minutes of administration but naphthylmedetomidine had no effect. The mean time to loss of righting reflex was 185 and 714 seconds after the administration of medetomidine and naphthylmedetomidine respectively. Conclusions and clinical relevanceThese results provide the first description of the effects of naphthylmedetomidine on cardiovascular and psychomotor functions in rabbits. Further work is required to reveal the anaesthetic sparing, analgesic or sedative effect of partial naphthylmedetomidine.

Electrocardiographic changes in rats undergoing thoracic surgery under combined parenteral anesthesia

To compare two protocols of combined parenteral general anesthesia, the authors analyzed electrocardiographic changes in anesthetized rats undergoing left pneumonectomy. One group of rats was anesthetized with a combination of medetomidine and ketamine (group 1, n = 10), and the other was injected with diazepam and ketamine (group 2, n = 10). Investigators obtained two electrocardiograms from each rat, one before surgery (5 min after anesthesia) and one after surgery (60 min after anesthesia). Anesthetic induction was quick for all rats, though four rats in group 2 died before surgery. Mean cardiac frequency and R-wave amplitude were significantly lower in rats in group 1 than in rats in group 2. Rats in group 1 received injections of atipamezole about 60 min after surgery, which reversed the effects of medetomidine; these rats regained voluntary respiratory movement more quickly than did rats in group 2. Two additional rats in group 2 died during postsurgical recovery. These results suggest that for thoracic surgery in rats, medetomidine-ketamine is an appropriate anesthetic combination, may be safer than diazepam-ketamine and yields a shorter recovery time.

The effects of medetomidine on the action of vecuronium in dogs anaesthetized with halothane and nitrous oxide

ObjectiveTo quantify the effects of medetomidine on the onset and duration of vecuronium-induced neuromuscular blockade in dogs. Study designRandomized, prospective clinical study. AnimalsTwenty-four, healthy, client-owned dogs of different breeds, aged between 6 months and 10 years and weighing between 5.0 and 40.0 kg undergoing elective surgery. MethodsDogs were randomly allocated to two groups. Pre-anaesthetic medication in group M+ was intramuscular acepromazine (ACP) 25 μg kg−1, morphine 0.5 mg kg−1 and medetomidine 5 μg kg−1. Group M− received ACP and morphine only, at the same dose rate. After induction with thiopental, anaesthesia was maintained with halothane in oxygen and nitrous oxide. End-tidal halothane concentration was maintained at 1.1%. Neuromuscular blockade was produced with intravenous vecuronium (50 μg kg−1) and monitored using a train of four stimulus applied at the ulnar nerve. The times taken for loss and reappearance of the four evoked responses (twitches [T]) were recorded. Normal and nonparametric data were analysed with an independent t-test and Mann-Whitney's U-test, respectively. ResultsThe fourth twitch (T4) disappeared at similar times in each group: 107 ± 19; [72–132] (mean ± SD; [range]) seconds in M+ and 98 ± 17 [72–120] seconds in M− dogs. The first twitch (T1) was lost at 116 ± 15; [96–132] seconds in group M+ and 109 ± 19; [72–132] seconds in M−. The fourth twitch returned significantly earlier in M+ dogs: 20.8 ± 3.8 [14–28] minutes compared with 23.8 ± 2.7 [20–27] minutes (p = 0.032). The duration of drug effect (T4 absent) was significantly shorter (p = 0.027) in M+ (18.9 ± 3.7 minutes) compared with M− dogs (22.2 ± 2.9 minutes). The recovery rate (interval between reappearance of T1 and T4) was significantly more rapid (p = 0.0003) in medetomidine recipients (3.0 ± 1.2 versus 5.2 ± 1.3 minutes).Conclusion and clinical relevance Medetomidine 5 μg kg−1 as pre-anaesthetic medication shortened the duration of effect of vecuronium in halothane-anaesthetized dogs and accelerated recovery, but did not affect the onset time. These changes are of limited clinical significance.

The effects of medetomidine hydrochloride on the electroretinogram of normal dogs

To determine the effects of a standardized intravenous dose of an alpha-2 agonist (Domitor, Orion Pharma, distributed by Pfizer Animal Health, Exton, PA) on the electroretinogram (ERG) response in normal dogs. Twenty-five normal dogs were used to collect ERG responses including a- and b-wave implicit times (IT) and amplitudes (AMP) before and after administration of medetomidine. Dogs were dark adapted for 20 min and ERGs were obtained using the HMsERG (RetVetCorp Inc., Columbia, MO). The QuickRetCheck protocol (Narfström) was employed to provide the following flash intensities: 10 mcd s/m(2), 3 cd s/m(2), and 10 cd s/m(2). ERGs were repeated after 375 microg/m(2) of medetomidine intravenously. Statistical analysis of the difference between the responses before and after medetomidine at all flash intensities was performed using a mixed effects model for anova. The P value for the effect of medetomidine on each of the ERG responses was < 0.01. The estimates of the effect of medetomidine were (+)1.35 ms, (-)23 microV, (+)3.16 ms, and (-)47 microV for the a-wave IT, a-wave AMP, b-wave IT, and the b-wave AMP, respectively. Medetomidine significantly prolongs the implicit time and lowers the amplitude response of both the a- and b-waves in normal dogs at all flash intensities examined. Clinically, however, medetomidine only minimally affects the retinal responses and is a viable choice for use in dog ERGs.

The effects of medetomidine and its reversal with atipamezole on plasma glucose, cortisol and noradrenaline in cattle and sheep

In the present study, we report the effect of medetomidine followed by atipamezole on plasma glucose, cortisol and noradrenaline in calves, cows and sheep. Eight calves, eight lactating dairy cows and eight adult female sheep were included in a crossover trial. The animals were injected i.v. with medetomidine (40 μg/kg), followed 60 min later by atipamezole i.v. (200 μg/kg) or saline. The wash-out period between experiments was 1 or 2 weeks. In every animal, medetomidine induced a marked hyperglycaemia, which was reversed by atipamezole. Cortisol levels increased significantly in cows and sheep, reaching levels 4–8-fold higher than the baseline levels 25–45 min after injection of medetomidine. Atipamezole did not affect the cortisol levels, except in sheep where an increase was observed. Plasma levels of noradrenaline decreased in cows and sheep after medetomidine injection, reflecting the inhibition of sympathetic activity by the drug. After injection of the antagonist, there was a large increase in noradrenaline levels. In conclusion, a high dose of medetomidine does not seem to reduce the overall endocrine stress response in cattle and sheep, which has previously been reported in other species.

Sedative and cardiopulmonary effects of medetomidine hydrochloride and xylazine hydrochloride and their reversal with atipamezole hydrochloride in calves

To assess the sedative and cardiopulmonary effects of medetomidine and xylazine and their reversal with atipamezole in calves. 25 calves. A 2-phase (7-day interval) study was performed. Sedative characteristics (phase I) and cardiopulmonary effects (phase II) of medetomidine hydrochloride and xylazine hydrochloride administration followed by atipamezole hydrochloride administration were evaluated. In both phases, calves were randomly allocated to receive 1 of 4 treatments IV: medetomidine (0.03 mg/kg) followed by atipamezole (0.1 mg/kg; n = 6), xylazine (0.3 mg/kg) followed by atipamezole (0.04 mg/kg; 7), medetomidine (0.03 mg/kg) followed by saline (0.9% NaCl; 6) solution (10 mL), and xylazine (0.3 mg/kg) followed by saline solution (10 mL; 6). Atipamezole or saline solution was administered 20 minutes after the first injection. Cardiopulmonary variables were recorded at intervals for 35 minutes after medetomidine or xylazine administration. At the doses evaluated, xylazine and medetomidine induced a similar degree of sedation in calves; however, the duration of medetomidine-associated sedation was longer. Compared with pretreatment values, heart rate, cardiac index, and PaO(2) decreased, whereas central venous pressure, PaCO(2), and pulmonary artery pressures increased with medetomidine or xylazine. Systemic arterial blood pressures and vascular resistance increased with medetomidine and decreased with xylazine. Atipamezole reversed the sedative and most of the cardiopulmonary effects of both drugs. At these doses, xylazine and medetomidine induced similar degrees of sedation and cardiopulmonary depression in calves, although medetomidine administration resulted in increases in systemic arterial blood pressures. Atipamezole effectively reversed medetomidine- and xylazine-associated sedative and cardiopulmonary effects in calves.

The effects of medetomidine on radial nerve blockade with mepivacaine in dogs

ObjectiveTo compare the sensory and motor effects of adding medetomidine to mepivicaine, administered either perineurally or systemically, for radial nerve block in dogs. Study designProspective randomized cross-over study. AnimalsSix healthy Beagles, aged 18.7 ± 6.3 months and weighing 10.4 ± 1.3 kg. MethodsDogs were anesthetized briefly with sevoflurane on three separate occasions and received each treatment administered in random order: mepivacaine 5 mg kg−1 perineurally around the radial nerve with saline 0.01 mL kg−1 intramuscularly (CONTROL); mepivacaine 5 mg kg−1 and medetomidine 0.01 mg kg−1 combined, perineurally with saline 0.01 mL kg−1 intramuscularly (MEDPN); mepivacaine 5 mg kg−1 perineurally around the radial nerve with medetomidine 0.01 mg kg−1 intramuscularly (MEDIM). All nerve blocks were performed with the aid of a nerve locator. Motor effects were evaluated based on the ability to bear weight. Sensory effects were evaluated by the response to a graded-electrical stimulus. These were evaluated at 5-minute intervals for the first hour, and at 10-minute intervals thereafter. Mean intervals were calculated as follows: time to motor block onset, duration of motor block, time to peak sensory block, duration of peak sensory block (i.e. period of no response to maximal stimulus intensity), and duration of residual sensory block (i.e. time to return to baseline sensory function). Treatment means were compared using a one-way analysis of variance for repeated measures and, where significant differences were noted, a Student–Newman–Keuls test was applied; p < 0.05 was considered significant. ResultsMedetomidine, administered either systemically or perineurally, significantly prolonged duration of peak motor block, peak sensory block, and residual sensory block compared with CONTROL. ConclusionMedetomidine prolonged sensory and motor blockade after radial nerve block with mepivacaine in dogs. Clinical relevanceMedetomidine may prove to be a useful adjunct to peripheral nerve blockade with local anesthetics.

Effects of medetomidine on doppler variables of major abdominal arteries in normal dogs

The purpose of this study was to evaluate the effects of medetomidine administration on the Doppler variables of abdominal arteries. The study population consisted of 20 healthy dogs. The haemodynamic effects of the medetomidine were defined using Doppler variables of the abdominal aorta, renal arteries, cranial mesenteric artery and celiac artery. The dogs were monitored continuously and different measurements were performed before medetomidine injection, at 10, 40 and 80 minutes after medetomidine medication and after atipamezole administration. Changes in the characteristic Doppler spectra of different vessels were more marked in the abdominal aorta, in which a greater reverse flow was found. There was a significant decrease in peak systolic velocity (PSV), end diastolic velocity (EDV), and mean velocity (MV) at ten minutes in every vessel studied and this effect persisted until atipamezole administration. Pulsatility index (PI) increased significantly in the abdominal aorta at ten minutes and persisted during the study until atipamezole administration. Resistive index (RI) did not vary significantly in any vessel. A significant decrease was found in flow volume of the abdominal aorta, the cranial mesenteric artery and the celiac artery at ten minutes, persisting until atipamezole administration. We conclude that medetomidine can be a good sedative in aiding sonographic evaluation of RI in all the abdominal vessels studied. On the other hand, the changes in other Doppler variables suggest that medetomidine administration causes significant hemodynamic differences between sedated and non-sedated dogs.

Effects of ketamine or medetomidine administration on quality of electroejaculated sperm and on sperm flow in the domestic cat

The effects of two commonly used drugs for anaesthesia in the domestic cat, ketamine and medetomidine, on features of electroejaculated semen and on sperm flow in this species were evaluated performing three experiments. This is the first study about these topics in the domestic cat. In Experiment 1, ketamine or medetomidine effects on cat sperm quality after collection by electroejaculation (E.E.) have been assessed in nine animals. Results showed that mean sperm concentration was significantly higher ( p < 0.01) after medetomidine than after ketamine administration. In Experiment 2, ketamine or medetomidine effects on sperm flow in 12 electroejaculated cats were studied. Mean sperm concentration and mean total number of spermatozoa resulted significantly higher ( p < 0.01) in medetomidine than in ketamine treated animals. The number of spermatozoa displaced in urethra was significantly higher ( p < 0.01) using medetomidine. No significant differences were observed in percentages of retrograde flow. In Experiment 3, ketamine or medetomidine effects on urethral sperm flow, without any stimulation for sperm collection, were evaluated. Data obtained showed a significantly higher ( p < 0.05) number of spermatozoa displaced in urethra after medetomidine than after ketamine injection. In conclusion, E.E. in the cat after medetomidine administration determined a higher number of spermatozoa per ejaculate than after ketamine administration, with a good pharmacological restriction and without increasing sperm retrograde flow.

Differences in response to anaesthetics and analgesics between inbred rat strains

Differences in response to analgesic and anaesthetic drugs can partly be attributed to variations in the genetic background of experimental animals. This study was carried out to determine differences in the response of inbred rat strains to a selection of analgesics and drugs used in anaesthetic protocols. A cross between the most contrasting strains can then be phenotyped in future studies in order to localize quantitative trait loci (QTLs) involved in analgesic/anaesthetic drug sensitivity. Eight inbred strains (n = 6 rats/strain) were selected for the study: the pigmented ACI, BN and COP strains and the albino F344, LEW, SHR, WAG and WKY strains. Each rat was injected intravenously with two analgesics (buprenorphine 0.05 mg/kg and nalbuphine 1 mg/kg) and three drugs used in anaesthetic protocols (propofol 25 mg/kg, medetomidine 50 microg/kg and ketamine 10 mg/kg), respectively, using a crossover design. Analgesic responses were assessed using an analgesiometric procedure. The sleep time of the rat and, where applicable, the interval between injection and loss of righting reflex were used to determine the anaesthetic response. Six out of eight strains responded significantly different from each other to the analgesic effect of buprenorphine with the ACI strain as hyper-responder. The tail withdrawal latency at 55 degrees C of the F344 and WKY rats using buprenorphine was not significantly different from baseline tail withdrawal latencies. In this study, all strains were non-responsive to the analgesic effects of nalbuphine. The response to all three drugs used in anaesthetic protocols differed significantly among the strains. The F344 and BN strains were relatively resistant to the sedative effects of medetomidine. Use of ketamine was abandoned in the ACI and BN strains when the first two animals of both strains died soon after induction. With all three drugs the sleep time of albino rats was significantly longer compared with that of the pigmented ones. We conclude that the results from this study can be used in future studies where QTLs for the sensitivity to anaesthetic/analgesic drugs are localized.

Effects of medetomidine on hepatic EROD activity in three species of fish

Medetomidine, an antifouling candidate, was investigated for its effects on cytochrome P4501A (CYP1A) activity in fish. Rainbow trout ( Oncorhynchus mykiss), turbot ( Psetta maxima), and Atlantic cod ( Gadus morhua) were exposed to medetomidine either via i.p. injection (<5 μmol (1 mg)/kg) or via water (<50 nM). Enzyme activity was measured as ethoxyresorufin- O-deethylase (EROD) activity in liver microsomes. There was a small (2–7-fold) increase in EROD activity in rainbow trout. In turbot, EROD activity increased (4-fold) after injection, while a non-significant (50%) decrease was observed after water exposure. No effects on EROD activities were observed in Atlantic cod. In vitro inhibition studies of EROD activities in liver microsomes from all three species showed that medetomidine was a very potent CYP1A inhibitor. Thus, median inhibition values (IC 50) were 35±10 nM for rainbow trout, 47±17 nM for turbot, and 111±70 nM for Atlantic cod. These observed effects suggest that medetomidine interferes with CYP1A-dependent metabolism of xenobiotics in these fish species.

α2‐Adrenoceptor subtypes involved in the regulation of catecholamine release from the adrenal medulla of mice

This study was carried out to elucidate which alpha(2)-adrenoceptor subtypes mediated the inhibition of noradrenaline and adrenaline release from the adrenal medulla of mice. Isolated adrenal medullae from wild-type and alpha(2A), alpha(2B) and alpha(2C)-adrenoceptor knockout (KO) mice were placed in superfusion chambers. Catecholamine overflow was evoked by 1,1-dimethyl-4-phenylpiperazinium (500 microM) in absence or in presence of the alpha(2)-adrenoceptor agonist medetomidine. The effect of medetomidine was tested in presence of the alpha-adrenoceptor antagonists rauwolscine, WB 4101, spiroxatrine, phentolamine and prazosin. In wild-type mice, medetomidine reduced noradrenaline and adrenaline overflow in a concentration-dependent manner (EC(50) in nM: 1.54 and 1.92; E(max) in % of inhibition: 91 and 94, for noradrenaline and adrenaline, respectively). The pK (D) values of the antagonists for noradrenaline overflow did not correlate with pK(D) values at alpha(2A), alpha(2B), or alpha(2C) binding sites. The pK (D) values of the antagonists for adrenaline overflow correlated positively with pK(D) values at alpha(2C) binding sites (opossum kidney cells). The effect of medetomidine (100 nM) on noradrenaline overflow was significantly reduced in all three alpha(2)KO mice (57, 54, 44 % inhibition, for alpha(2A), alpha(2B), and alpha(2C), respectively), whereas the effect of medetomidine on adrenaline overflow was greatly reduced in alpha(2C)KO mice (14 % inhibition). In the adrenal medulla of mice, all three alpha(2)-adrenoceptor subtypes (alpha(2A), alpha(2B), and alpha(2C)) play an equal role in the inhibition of noradrenaline overflow, whereas the alpha(2C)-adrenoceptor is the predominant alpha(2)-adrenoceptor subtype involved in the inhibitory mechanism controlling adrenaline overflow.

Effects of a candidate antifouling compound (medetomidine) on pheromone induced mate search in the amphipod Corophium volutator

Environmental hazards associated with traditional, toxic antifouling coatings based on heavy metals calls for the development of alternative, environmentally acceptable antifouling compounds. Medetomidine ((±)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole) is a candidate antifouling biocide which impedes settlement of barnacles in the nanomolar range. Prior to introducing novel biocides it is of great importance to consider potential effects on non-target organisms. This study is the first to investigate the effects of medetomidine on the amphipod Corophium volutator, specifically effects on male mate search behaviour. In a laboratory, Y-maze bioassay, C. volutator males were allowed to follow female pheromones after 24 h exposure to 0 (control), 0.01 and 0.1 μg mL −1 medetomidine. We found that exposure to medetomidine at both concentrations significantly reduced pheromone induced mate search (by 42–71%), with fewer males crawling towards female odour. The results obtained indicate that medetomidine may impair the reproductive fitness of non-target crustaceans, an aspect that needs to be considered before further commercialisation.

Cerebral state monitoring in Beagle dogs sedated with medetomidine

ObjectiveTo provide experience of monitoring the level of hypnosis with the Cerebral State Monitor (CSM), a device extracting a single numerical variable between 0 and 100 from the electroencephalogram in dogs sedated with medetomidine during dental scale removal. Study designProspective observational study. Animals Nine female Beagle dogs weighing 13.3 ± 1.3 kg. MethodsCerebral state index (CSI) and burst suppression ratio (BSR) were recorded from sub-dermal needle electrodes in dogs sedated after subcutaneous injection of 114 ± 11 μg kg−1 medetomidine. Ten minutes after injection CSI monitoring began, and after 5 minutes, dental scale removal with an ultrasonic probe was started. After approximately 30 minutes, the effects of medetomidine were antagonized with atipamezole. ResultsThe CSI had a median value of 43 (range 40–56) in undisturbed sedated dogs. During dental scale removal, CSI increased to a median value of 99 (range 92–100). The BSR in undisturbed sedated dogs ranged from 2 to 15, but fell to zero during dental scale removal. ConclusionsStimulation during dental scale removal might be expected to reduce the level of sedation and hypnosis in dogs to which medetomidine had been administered. The concurrent increase in CSI and decrease in BSR suggested that a higher CSI was associated with arousal from sedation and a reduction in the depth of hypnosis. More studies are needed to validate CSI in order to better understand the functioning of this monitor. Clinical relevance The CSM shows promise for monitoring the degree of sedation and hypnosis during anaesthesia, and after adequate validation, could contribute to the refinement of anaesthetic techniques in animals.

Cardiopulmonary effects of medetomidine or midazolam in combination with ketamine or tiletamine / zolazepam for the immobilisation of captive cheetahs (Acinonyx jubatus)

Captive cheetah (Acinonyx jubatus) scheduled for either general health examination or dental surgery were immobilised with combinations of medetomidine-ketamine (K/DET, n = 19), midazolam-ketamine (K/MID, n = 4) or medetomidine-tiletamine-zolazepam (Z/DET, n = 5). Induction time and arterial blood pressure was not statistically significantly (P > 0.05) different between treatment groups. Transient seizures were observed in the K/DET treated animals during induction. Hypertension was present in all groups during anaesthesia with mean (+/- SD) systolic pressure of 30.7 +/- 5.0 kPa for the K/DET group, 27.7 +/- 2.7 kPa for the K/MID group, and 33.1 +/- 4.6 kPa for the Z/DET group. Heart rate was statistically significantly (P < 0.05) lower in the K/DET group (69 +/- 13.2 beats/min) compared to the K/MID group (97 +/- 22.6 beats/min), and ventilation rate was statistically significantly (P < 0.05) lower in the K/MID group (15 +/- 0.0 breaths/min) compared with the K/DET group (21 +/- 4.6). A metabolic acidosis and hypoxia were observed during anaesthesia when breathing air. Oxygen (O2) administration resulted in a statistically significant (P < 0.05) increase in the arterial partial pressure of carbon dioxide (hypercapnoea), arterial partial pressure of O2, and % oxyhaemoglobin saturation.

Evalution of hormonal metabolic and cardiorespiratory effects of medetomidine in one humped camels /

Evalution of hormonal metabolic and cardiorespiratory effects of medetomidine in one humped camels /

Effect of medetomidine on respiration and minimum alveolar concentration in halothane- and isoflurane-anesthetized dogs

To evaluate the effect of medetomidine on minimum alveolar concentration (MAC), respiratory rate, tidal volume, minute volume (V(M)), and maximum inspiratory occlusion pressure (IOCP(max)) in halothane- and isoflurane-anesthetized dogs. 6 healthy adult dogs (3 males and 3 females). The MAC of both inhalants was determined before and 5, 30, and 60 minutes after administration of medetomidine (5 microg/kg, IV). Dogs were subsequently anesthetized by administration of halothane or isoflurane and administered saline (0.9% NaCl) solution IV or medetomidine (5 microg/kg, IV). Respiratory variables and IOCP(max) were measured at specific MAC values 15 minutes before and 5, 30, and 60 minutes after IV administration of medetomidine while dogs breathed 0% and 10% fractional inspired carbon dioxide (FICO2). Slopes of the lines for VM/FICO2 and IOCP(max)/FICO2 were then calculated. Administration of medetomidine decreased MAC of both inhalants. Slope of V(M)/FICO2 increased in dogs anesthetized with halothane after administration of medetomidine, compared with corresponding values in dogs anesthetized with isoflurane. Administration of medetomidine with a simultaneous decrease in inhalant concentration significantly increased the slope for V(M)/FICO2, compared with values after administration of saline solution in dogs anesthetized with halothane but not isoflurane. Values for IOCP(max) did not differ significantly between groups. Equipotent doses of halothane and isoflurane have differing effects on respiration that are most likely attributable to differences in drug effects on central respiratory centers. Relatively low doses of medetomidine decrease the MAC of halothane and isoflurane in dogs.

Effects of medetomidine, a novel antifouling agent, on the burrowing bivalve Abra nitida (Müller)

The effects of medetomidine, a novel antifouling candidate, on the burrowing bivalve Abra nitida were studied. The burrowing behaviour, sediment reworking activity and faeces production were assessed after 24 h exposure of A. nitida to sublethal concentrations of medetomidine. Medetomidine caused a significant decrease in the burrowing response and in the sediment reworking activity. The median effective concentrations (EC 50) were 430 nM (86 μg/l) and 4.4 nM (0.9 μg/l), respectively. No effects on the faeces production were detected. Although significant effects of medetomidine on A. nitida were registered, a reversibility of the effects was observed when 24 h-exposed animals were incubated in clean seawater and sediment for 24 h. Considerations relating to the future commercialisation of medetomidine for antifouling purposes are discussed.

The influence of the time course of inflammation and spinalization on the antinociceptive activity of the α 2-adrenoceptor agonist medetomidine

The purpose of the present study was to investigate the influence of the time course of inflammation and the implication of spinal and supraspinal sites on the antihyperalgesic effects of the α 2-adrenoceptor agonist medetomidine. Behavioral experiments showed a more intense antihyperalgesia in the phase of maintenance of inflammation than in the early or resolution stages. Maximum effect, without sedation, was observed with a dose of 40 μg/kg (66 ± 12% and 76 ± 15% reduction of mechanical and thermal hyperalgesia). No change was observed in the paw swelling, indicating that its effects were not secondary to a reduction of inflammation. In electrophysiological experiments, the effect was more pronounced in animals with an intact spinal cord than in spinalized animals (max. effects of 2 ± 0.7% vs. 48 ± 11% of control, noxious mechanical stimulation). We conclude that the antihyperalgesic effect of medetomidine depends on the time course of inflammation and that it is mainly located supraspinally.