Effects Of Atipamezole Research Articles

Effects of atipamezole and flumazenil on stress-related hormonal and metabolic responses in cats anesthetized with medetomidine, midazolam, ketamine and isoflurane undergoing ovariohysterectomy and castration

Effects of atipamezole and flumazenil on stress-related hormonal and metabolic responses in cats anesthetized with medetomidine, midazolam, ketamine and isoflurane undergoing ovariohysterectomy and castration

Effects of an anesthetic mixture of medetomidine, midazolam, and butorphanol and antagonism by atipamezole in rabbits

Medetomidine (MED), midazolam (MID), and butorphanol (BUT) mixed anesthetic (MMB) has been used in laboratory animals since ketamine (KET) was designated as a narcotic in Japan in 2007. We previously reported that MMB produced anesthetic effects in mice and rats. We also demonstrated the efficacy of atipamezole (ATI), an antagonist of MED produced a quick recovery from anesthesia. Anesthetics have various anesthetic effects among different animal species. However, there is little information regarding its effects in rabbits. In the present study, we examined anesthetic effects of MMB compared to KET and xylazine mixed anesthetic (KX). We examined the antagonistic effects of ATI by intramuscular (IM) or intravenous (IV) injection in rabbits. We used the anesthetic score to measure surgical anesthetic duration and recovery time from anesthesia. During the experiments, we measured heart rate, respiratory rate, O2-saturation, and blood pressure. We found there were no significant differences in anesthetic duration and recovery time between MMB and KX. There were no significant differences in heart rate after administration of MMB or KX. Systolic blood pressure at 10 min after administration of MMB was higher than that of KX. The antagonistic effect of ATI by IV injection worked faster than that by IM injection. Overall, MMB is a useful drug that can induce similar anesthetic effects to KX and has an antagonist of ATI that makes rabbits quickly recover from anesthesia. These results may contribute to the welfare of laboratory animals, especially rabbits.

Effects of an anesthetic mixture of medetomidine, midazolam, and butorphanol in rats-strain difference and antagonism by atipamezole.

An anesthetic mixture of medetomidine (MED), midazolam (MID), and butorphanol (BUT) has been used in laboratory animals. We previously reported that this anesthetic mixture produced closely similar anesthetic effects in BALB/c and C57BL/6J strains. We also demonstrated the efficacy of atipamezole (ATI), an antagonist of MED that produced quick recovery from anesthesia in mice. Anesthetics have various anesthetic effects among animal strains. However, the differences in the effects of anesthetic mixtures in rats are unclear. In the present study, we first examined effects of the abovementioned anesthetic mixture using three different rat strains: Wistar (WST), Sprague-Dawley (SD), and Fischer 344 (F344). Second, we examined how different dosages and optimum injection timing of ATI affected recovery from anesthesia in rats. We used the anesthetic score to measure anesthetic duration and a pulse oximeter to monitor vital signs. We found no significant differences in anesthetic duration among the three different strains. However, recovery from anesthesia in the SD strain took significantly longer than in the other strains. The antagonistic effects of ATI (0.15 mg/kg and 0.75 mg/kg) were equivalent when administered at 30 min after anesthetic mixture administration. The antagonistic effects of ATI 0.75 mg/kg were stronger than those of ATI 0.15 mg/kg at 10 min after anesthetic mixture administration. This anesthetic mixture is a useful drug that can induce similar anesthetic effects in three different strains and has an antagonist, ATI, that makes rats quickly recover from anesthesia. These results may contribute to the welfare of laboratory animals.

Low doses of α2‐adrenoceptor antagonists augment spinal morphine analgesia and inhibit development of acute and chronic tolerance

Ultra-low doses of opioid receptor antagonists augment spinal morphine antinociception and block the induction of tolerance. Considering the evidence demonstrating functional and physical interactions between the opioid and alpha(2)-adrenoceptors, this study investigated whether ultra-low doses of alpha(2)-adrenoceptor antagonists also influence spinal morphine analgesia and tolerance. Effects of low doses of the competitive alpha(2)-adrenoceptor antagonists-atipamezole (0.08, 0.8 ng), yohimbine (0.02, 2 ng), mirtazapine (0.02 ng) and idazoxan (0.08 ng) were investigated on intrathecal morphine analgesia, as well as acute and chronic morphine antinociceptive tolerance using the rat tail flick and paw pressure tests. At doses markedly lower than those producing alpha(2)-adrenoceptor blockade, atipamezole, yohimbine, mirtazapine and idazoxan, prolonged the antinociceptive effects of morphine. When co-administered with repeated acute spinal injections of morphine, all four agents blocked the induction of acute tolerance. Co-injection of atipamezole with morphine for 5 days inhibited the development of tolerance in a chronic treatment paradigm. Spinal administration of atipamezole also reversed established antinociceptive tolerance to morphine as indicated by the restoration of morphine antinociceptive potency. The effects of atipamezole on spinal morphine tolerance were not influenced by treatment with 6-hydroxydopamine. Low doses of competitive alpha(2)-adrenoceptor antagonists can augment acute morphine analgesia and block or reverse tolerance to spinal administration of morphine. These actions are interpreted in terms of their interaction with an opioid-alpha(2)-adrenoceptor complex, whose activity may have a function in the genesis of analgesic tolerance.

Effects of Atipamezole and Naloxone on Electroencephalographic Spectral Edge Frequency 95 in Dogs Sedated by Acupuncture at GV20 and Yintang Point

The purpose of this study was to evaluate the antagonism of acupuncture-induced sedation by electroencephalographic spectral edge frequency (SEF) 95 in 10 healthy intact male Miniature Schnauzer dogs (4.2-6.1kg; 2-3 years old) without neurological disorder. The GV20 and Yintang acupoints were administered for 20 min. While the dogs were conscious, SEF 95 baseline values were recorded at 2-min intervals for 4 min. Then acupuncture was administered at the GV20 and Yintang acupoints. During the acupuncture procedure, the SEF 95 values were recorded at 2-min intervals for 10 min. Subsequently, antagonist drugs, naloxone and atipamezole, were administered through the cephalic vein. The SEF 95 values were then measured again at 2-min intervals for 10 min. Those values were found to be significantly increased after administration of atipamezole in dogs sedated by acupuncture at the GV20 and Yintang acupoints (p<0.05). However, the SEF 95 values in the naloxone groups did not show any significant changes before and after administration of the antagonist. It was concluded that sedation induced by acupuncture at the GV20 and Yintang acupoints might be partially associated with the alpha(2)-adrenergic system.

Effects of atipamezole — a selective α2‐adrenoceptor antagonist — on cardiac parasympathetic regulation in human subjects

1 This double-blind, cross-over, placebo-controlled study on six healthy male volunteers was designed to evaluate the effects of alpha2-adrenoceptor antagonism on cardiac parasympathetic regulation. 2 The subjects received atipamezole intravenously as a three-step infusion, which aimed at steady-state serum concentrations of 10, 30 and 90 ng ml(-1) at 50-min intervals. 3 Drug effects were assessed with repeated recordings of blood pressure and electrocardiogram, in which the high-frequency (0.15-0.40 Hz) R-R interval variation is supposed to reflect cardiac parasympathetic efferent neuronal activity. 4 At the end of the three steps of the infusion, the mean (+/-SD) concentrations of atipamezole were 10.5 (3.9), 26.8 (5.6) and 81.3 (21.1) ng ml(-1). 5 Within this concentration range, atipamezole appeared to reduce slightly the high-frequency R-R interval fluctuations, indicating a minor vagolytic effect in the heart. 6 Atipamezole increased systolic and diastolic arterial pressure, on average by 20 and 14 mmHg (maxima at the second step of the infusion), which evidently reflects an overall sympathetic augmentation.

Atipamezole, an α 2-adrenoceptor antagonist, augments the effects of l-DOPA on evoked dopamine release in rat striatum

The effects of atipamezole, an α 2-adrenoceptor antagonist, l-3,4-dihydroxyphenylalanine ( l-DOPA) and the combination of these drugs on dopamine overflow were studied in dopaminergic presynaptic terminals of rat caudate and nucleus accumbens. Dopamine overflow evoked by 100 pulses of electrical stimulation of the medial forebrain bundle at a low (20 Hz) and high (50 Hz) frequency was measured by in vivo voltammetry. l-DOPA (15 mg/kg) increased dopamine overflow in the caudate nucleus, but this dose had no effects in the nucleus accumbens. Atipamezole (300 μg/kg) had no effects on its own on dopamine overflow, but it did increase the size of the readily releasable storage pool and the effects of l-DOPA treatment in both structures. The combination of the drugs increased dopamine overflow to a larger extent at high compared to low stimulation frequencies. We conclude that the rat caudate nucleus is more sensitive than the nucleus accumbens to the effects of l-DOPA, and the effects of l-DOPA treatment might be effectively enhanced by antagonism of α 2-adrenoceptors.

Effects of atipamezole, detomidine and medetomidine on release of steroid hormones by porcine adrenocortical cells in vitro.

The 4-substituted imidazole type alpha2-adrenoceptor ligands atipamezole, detomidine, and medetomidine were screened for actions on the release of aldosterone by a suspension of porcine adrenocortical cells with deoxycorticosterone (1 microM) as substrate. Progesterone, pregnenolone or corticosterone (all at 1 microM) were also used as substrates. With pregnenolone as substrate, drug-induced effects on the output of nine steroids (aldosterone, corticosterone, cortisol, deoxycortisol, testosterone, progesterone, 17alpha-hydroxyprogesterone, androstenedione, dehydroepiandrosterone) were monitored simultaneously. The alpha2-adrenoceptor antagonist atipamezole was a potent inhibitor of aldosterone release (range 10-1000 nM). The sedative alpha2-adrenoceptor agonists medetomidine and detomidine also inhibited aldosterone release (range 10-1000 nM). With pregnenolone as substrate, the inhibition induced by 4-substituted imidazoles of the release of corticosterone and cortisol was more pronounced than that of aldosterone. Androstenedione and deoxycortisol release was enhanced. The 4-substituted imidazoles atipamezole, detomidine, and medetomidine inhibited mitochondrial cytochrome P450(11beta/18) in vitro. This inhibition was unrelated to their alpha2-adrenoceptor actions. The 4-substituted imidazole type alpha2-adrenoceptor ligands used to control sedation/anaesthesia can alter the steroid-based defence mechanisms of the body.

Effects of atipamezole and yohimbine on medetomidine-induced central nervous system depression and cardiorespiratory changes in lambs

SUMMARY We compared the ability of 2 α2-adrenergic receptor antagonists, atipamezole and yohimbine, to reverse medetomidine-induced CNS depression and cardiorespiratory changes in lambs. Twenty lambs (7.8 ± 2.6 kg) were randomly allotted to 4 treatment groups (n = 5). Each lamb was given medetomidine (30 μg/kg of body weight, IV), followed in 15 minutes by IV administration of atipamezole (30 or 60 μg/kg), yohimbine (1 mg/kg), or 0.9% NaCl (saline) solution. Medetomidine caused lateral recumbency in 1 to 2 minutes in all treated lambs. Medetomidine significantly (P &lt; 0.05) decreased heart rate at 5 and 10 minutes after its administration. Heart rate remained above 120 beats/min, and severe bradycardia (≤ 70 beats/min) and other arrhythmias did riot occur throughout the study. Medetomidine also induced tachypnea in all treated lambs. The tachypnea was abolished by atipamezole and yohimbine, but not by saline solution administration. The medetomidine-induced tachypnea did not significantly affect arterial pH and Paco2. Arterial oxygen tension was within acceptable range (Pao2, = 71 to 62 mm of Hg), but was lower than expected. Administration of atipamezole, yohimbine, or saline solution did not change Pao2, significantly. Lambs treated with 30 or 60 μg of atipa- mezole/kg were able to walk unassisted in 2.4 ± 0.4 and 2.3 ± 0.7 minutes, respectively, whereas yohimbine- and saline-treated lambs did not walk unassisted until 15.6 ± 2.7 and 73.0 ± 6.8 minutes later, respectively. Results of this study indicated that medetomidine is a potent CNS depressant in lambs. Atipamezole at dosage of 30 or 60 μg/kg was equally effective, and was more effective in antagonizing medetomidine-induced CNS depression than was yohimbine.

Food intake and rumen motility in dwarf goats. Effects of atipamezole on the inhibitory effects induced by detomidine, medetomidine and romifidine.

The effects of some alpha 2-adrenoceptor agonists and of the alpha 2-adrenoceptor antagonist atipamezole on food intake and ruminal contractions were studied in dwarf goats. Detomidine, 0.2 microgram/kg per min for 10 min, failed to modify food intake during either the first or second observation period (0-30 min and 180-210 min after drug infusion, respectively). Given at a higher dose rate (0.4 microgram/kg per min for 10 min), the drug inhibited food consumption during the first observation period, but stimulated food intake during the second period. A similar pattern was observed after IV infusion with medetomidine (0.2 microgram/kg per min for 10 min), romifidine (0.4 microgram/kg per min for 10 min) or xylazine (1 microgram/kg per min for 10 min). The alpha 2-antagonist atipamezole (2 micrograms/kg per min for 10 min) failed to modify food intake during either the first or second observation period. After treatment with atipamezole, the effects of alpha 2-agonists on feeding behaviour were completely antagonized. The alpha 2-agonists administered at similar dose rates to those used in the food intake experiments induced bradycardia, decreases in body temperature and inhibition of ruminal contractions. The inhibition of ruminal contractions induced by romifidine was partly antagonized by atipamezole pre-treatment. These findings demonstrate that the alpha 2-agonist-induced changes in ruminal contractions do not simply cause changes in feeding behaviour. The drop in body temperature induced by alpha 2-agonists was prevented by atipamezole pre-treatment, whereas the induced bradycardia was not modified by this alpha 2-antagonist.

犬のメデトミジン鎮静効果に対するアチパメゾールおよびヨヒンビンのきっ抗効果

犬のメデトミジン鎮静効果に対するアチパメゾールおよびヨヒンビンのきっ抗効果

Comparison of dexmedetomidine and midazolam sedation and antagonism of dexmedetomidine with atipamezole

Study Objective: To evaluate the effects of dexmedetomidine, an alpha-2 agonist, as an intravenous sedative drug and the effects of atipamezole, an alpha.-2 antagonist, on recovery. Design: Randomized, double-blind study with three parallel groups. An open dose-finding study preceded it to optimize the atipamezole dose. Setting: Outpatient operating room at the gynecologic and obstetric university hospital in Helsinki, Finland. Patients: Seventy-two healthy women scheduled for legal termination of pregnancy. Interventions: Patients were assigned to one of three groups of 24 patients each to receive either dexmedetomidine 2 μg/kg and atipamezole 50 μg/kg; dexmedetomidine 2 μg/kg and saline; or midazolam 0.15 mg/kg and saline. In addition to paracervical block, each patient received two different study drugs: study drug 1 was a sedative agent (either dexmedetomidine or midazolam), administered before the procedure. If the sedation was not deep enough and the patient reacted to the procedure, a low dose of propofol was administered. Study drug 2 was a reversing agent or a placebo, administered following the procedure. Measurements and Main Results: The mean time to regain consciousness was shorter in the dexmedetomidine-atipamezole and the dexmedetomidine-saline groups compared with the midazolam group. Postoperative sedation, tested both by subjective and objective assessments, decreased more quickly in the dexmedetomidine-atipamezole group compared with the dexmedetomidine-saline and the midazolam groups. Conclusion: Atipamezole is an effective antagonist for reversing psychomotor impairment following dexmedetomidine sedation.

Dose- and parameter-dependent effects of atipamezole, an α2-antagonist, on the performance of rats in a five-choice serial reaction time task

The present study investigated whether atipamezole (ATI), a potent α 2-adrenoceptor antagonist that increases the release of noradrenaline in brain, improves attention in rats. Thus, the effects of ATI on the performance of adult male rats in the five-choice serial reaction time task were studied. Food-deprived rats were trained to detect and respond to brief flashes of light presented randomly in one of five spatially diverse locations. The effects of single-dose administration of ATI (0.03–3.0 mg/kg) on the performance of rats under different parametric manipulations of the task were tested: 1) the visual stimuli were presented at unpredictable intertrial intervals (ITIs) or b) the intensity (brightness) of visual stimuli was reduced, thus placing an additional load on attentional processing for animals. Presenting the stimuli earlier than normally or reducing its intensity markedly impaired the choice accuracy of rats. At doses of 0.03, 0.3, and 1.0 mg/kg, ATI improved the choice accuracy of rats when tested using reduced stimulus intensity. ATI 3.0 mg/kg did not affect accuracy performance when tested using reduced stimulus intensity but impaired it when tested using unpredictable ITIs. The other doses of ATI (0.03, 0.3, and 1.0 mg/kg) did not markedly affect choice accuracy of rats tested using unpredictable ITI. Our results could be explained by the assumption that an acute, systemic administration of ATI affects arousal mechanisms and facilities the processing of visual stimuli related to reward.

Effects of Atipamezole, an ??-Adrenoceptor Antagonist, on the Anesthesia Induced by Barbiturates and Medetomidine

Effects of Atipamezole, an ??-Adrenoceptor Antagonist, on the Anesthesia Induced by Barbiturates and Medetomidine

Effects of atipamezole, an α2-adrenoceptor antagonist, on the performance of rats in a five-choice serial reaction time task

The present study investigates whether pharmacological activation of the noradrenergic system improves attention. The effects of atipamezole, a potent α2-adrenoceptor antagonist, on the performance of adult male rats in the five-choice serial reaction time task were studied. Before drug testings, food-deprived rats were trained to detect and respond to brief flashes of light presented randomly by the computer in one of five spatially diverse locations until a stable level of performance had been reached (about 3 months). Single-dose administration of atipamezole (0.03–3.0 mg/kg) slightly increased the number of premature and preservative responses during the intertrial interval and slightly decreased the reaction times to incorrect responses, indicating increased behavioral activation. Atipamezole did not affect discriminative accuracy. However, in a subpopulation of rats with the poorest discriminative accuracy according to pretest performance seven of eight rats improved their discriminative accuracy when treated with 0.3 mg/kg atipamezole as compared to controls. At the other doses tested, no improvement was found. The present results suggest that acute administration of atipamezole, an α2-adrenoceptor antagonist, slightly increases behavioral activation, although the effects on baseline performance in the task measuring selective attention are modest.

Effects of atipamezole on xylazine sedation in ponies.

Atipamezole antagonism of xylazine sedation was evaluated in six ponies. Atipamezole (0.15 mg/kg) or saline was injected intravenously 15 minutes after the ponies had been sedated with xylazine (1.0 mg/kg). Arterial blood pressure and gases, pulse and respiratory rates, the electrocardiogram, nose-to-ground distance and a subjective sedation score were recorded. The pretreatment nose-to-ground distance and PaO2 returned to normal sooner after atipamezole than after saline and the ponies' appetite and normal locomotion also recovered sooner. No significant differences were observed between the effects of saline and atipamezole on the other measurements.

The effects of atipamezole, an Alpha-2 antagonist, on the performance of young and aged rats in the delayed nonmatching to position task

The present experiments were undertaken to study whether pharmacological activation of the noradrenergic system would improve age-related deficits in short-term memory. Thus, we investigated the effects the single dose administration (0.1, 0.3, 0.9 and 2.7 mg/kg, subcutaneously) or atipamezole, a specific alpha-2 adrenoceptor antagonist, had on the performance of young and aged rats in a delayed nonmatching to position task. After substantial training, aged rats made more errors at longer delays (4-30 seconds) than did young rats, although the percent correct responses at short delays (0-2 seconds) did not differ between young and aged rats. Atipamezole (0.1-0.9 mg/kg) did not improve the performance of young and aged rats in this task. Moreover, the highest dose (2.7 mg/kg) used increased the number of omissions and increased the latency to collect food pellets, indicating disruption of the performance of rats in this task. According to the present results, alpha-2 antagonist (administered peripherally at a single dose), which increases the release of noradrenaline, did not improve age-related deficit in short-term memory in rats.

Effects of atipamezole and tetrahydroaminoacridine on nucleus basalis lesion-induced EEG changes

In the present study the effect of combined anticholinesterase [tetrahydroaminoacridine (THA)] and alpha 2-antagonist (atipamezole) treatment were evaluated on nucleus basalis (NB, quisqualic acid) lesion-induced EEG activity changes. THA (1,3 and 6 mg/kg; an anticholinesterase) and atipamezole (Ati: 3 and 10 mg/kg; an alpha 2-antagonist) suppressed dose-dependently NB lesion-induced high-voltage spindle activity and increase in slow/fast activity ratio. A combination of THA (3 mg/kg) and Ati (3 or 10 mg/kg) more effectively suppressed NB lesion-induced HVS activity than either of the drugs alone did. The present results suggest that alpha 2-noradrenergic and NB cholinergic systems interact in the regulation of slow wave and HVS activity and that combined stimulation of these systems more effectively stabilize NB lesion-induced EEG changes.

Effects of atipamezole, an alpha-2 antagonist, on memory retrieval in the rat

Effects of atipamezole, an alpha-2 antagonist, on memory retrieval in the rat

Comparative Trial of Xylazine and Medetomidine as Preanaesthetics Prior to Na Pentobarbital Anaesthesia in Dogs

The effects of medetomidine [20 and 40 micrograms/kg of body weight (BWT) i.m.] followed by sodium pentobarbital were assessed and compared with the effects of xylazine (1 mg/kg of BWT i.m.) in three groups each of 6 dogs. The effects of atipamezole as a specific antidote after anaesthesia were also studied. Medetomidine produced a reliable sedation which was clinically comparable with the xylazine premedication. 40 micrograms/kg medetomidine induced lower induction (non-significantly), total (p less than 0.05), anaesthetic (non-significantly) and anaesthetic per hour (non-significantly) doses of Na pentobarbital compared to the 20 micrograms/kg medetomidine and the xylazine protocols. No significant differences in the total number of re-injections were found between the sedative protocols although a gradual increase in number of re-injections per hour was observed. Significant decreases in heart and respiration rates were noticed during anaesthesia in all groups (p less than 0.01). The heart and respiration rates during anaesthesia in the 40 micrograms/kg medetomidine group were always significantly lower compared to the xylazine group. Body temperature decreased gradually in time during anaesthesia in all groups (p less than 0.05 after 1 hour, p less than 0.01 after 2 and 3 hours) without significant differences between the groups. The extubation time in the medetomidine protocols without antagonisation was significantly greater (p less than 0.01) than the extubation time after antagonisation with atipamezole.