Atipamezole Hydrochloride Research Articles

Cloridrato de dexmedetomidina como medicação pré- anestésica ou sedativo em cães

Relata-se, dois casos, sendo que no primeiro, realizou-se cirurgia de OVH eletiva. Como MPA,utilizou-se 2,5 mcg/kg de cloridrato de dexmedetomidina e 0,2 mg/kg de cloridrato de metadonaIM. A recuperação anestésica foi tranquila e sem complicações e o animal foi extubado apóscinco minutos, recebendo alta do centro cirúrgico 30 minutos depois. No segundo caso,realizou-se cirurgia de sepultamento da glândula da terceira pálpebra. Como sedativo, utilizouse 3,5 mcg/kg de cloridrato de dexmedetomidina e, como analgésico, 0,2 mg/kg de cloridratode metadona IM. Ao término do procedimento cirúrgico, administrou-se 0,4 mcg/kg decloridrato de atipamezole IM. Decorridos 15 minutos o paciente recuperou-se completamente,podendo ser encaminhado para alta cirúrgica. Os dois procedimentos transcorreram comvalores de PAS e bradicardia elevados,efeitos característicos do uso da dexmedetomidina. Noprimeiro caso a PAS se manteve entre 150 e 180 mmHg, no segundo, entre 160 e 180 mmHg.A partir dos casos relatados, conclui-se que o emprego da dexmedetomidina foi benéfico,proporcionando adequada medicação pré-anestésica e sedação nos referidos pacientes.

Puppy survival and vigor associated with the use of low dose medetomidine premedication, propofol induction and maintenance of anesthesia using sevoflurane gas-inhalation for cesarean section in the bitch

The safety of an anesthetic protocol consisting of medetomidine hydrochloride (7 μg/kg iv) as premedicant, propofol, (1–2 mg/kg iv) as induction agent and sevoflurane, at 2% in oxygen for maintenance of anesthesia was studied in 292 cesarean sections (CSs) and 2232 puppies delivered. Medetomidine effects were reversed using atipamezole hydrochloride at 50 μg/puppy sc immediately following delivery and in the bitch iv immediately following surgery. The protocol's safety for puppies was expressed using survival immediately, 2 h and 7 d after delivery, and Apgar scores (measurement starting 15 min after delivery of the last puppy). The maternal survival rate was established immediately, 2 h and 7 d after cesarean section (CS). The CSs included 148 on Boerboel, 84 on English bulldog and 60 on other purebred bitches, which resulted in 1378, 541 and 313 puppies, respectively. Boerboel, English bulldog and other purebred bitches yielded 97.39%, 96.67% and 91.69% live puppies at delivery, 95.43%, 88.35% and 89.78% alive by 2 h and 89.19%, 79.11% and 84.03% alive by 7 d. Sixteen (1.16%), 32 (5.59%) and 4 (1.28%) malformed Boerboel, English bulldog and other purebred puppies were euthanized. Thirty five, 18 and 26, Boerboel, English bulldog and other purebred puppies were stillborn respectively, of which 12, 9 and 15, respectively had been discovered dead upon ultrasound examination immediately before CS. After correction for fetuses found dead on ultrasound examination and malformed euthanized puppies, 98.21%, 95.60% and 94.30% of Boerboel, English bulldog and other purebred puppies survived until 2 h and 91.78%, 87.17% and 88.26% until 7 d. Two-hour survival rates are negatively correlated to the proportion of puppies in a litter with scores of 8 or below (r = 0.14, P = 0.01, n = 292 litters) and tends to be positively correlated to the lowest Apgar score in a litter (r = 0.11, P = 0.05, n = 292 litters). This study shows that medetomidine hydrochloride in the protocol used is a safe premedicant in bitches prior to cesarean section and is associated with good puppy vigor as well as 2 h and 7 d puppy survival rates. The use of medetomidine as premedicant permitted use of less than half the dose of propofol usually required as induction agent.

Effects of alpha-adrenergic agonists on pain modulation in diffuse noxious inhibitory control.

Diffuse noxious inhibitory control (DNIC) is thought to be mediated by neural networks in supraspinal brain structures. The descending antinociceptive system (DAS) is an important component of the DNIC neural network, but the precise structure of the neural network and the related neurotransmitters have not been examined. The study was designed to examine whether systemic administration of the adrenergic agonists dexmedetomidine (DEX) and phenylephrine (PE) influences DNIC in the rat. Changes in the C-fiber reflex evoked by electromyographic activity were recorded following noxious tail immersion in hot water. Inhibition of the C-fiber reflex by the conditioning stimuli was reduced from 77.1 +/- 22.6% to 26.6 +/- 38.2% with continuous administration of DEX, and restored to 58.3 +/- 29.2% by intramuscular injection of atipamezole hydrochloride(APZ), a selective alpha 2-adrenoceptor antagonist. Inhibition of the C-fiber reflex was reduced from 75.6 +/- 25.8% to 22.7 +/- 38.9% with continuous administration of PE, and restored to 84.9 +/- 9.7% by intramuscular injection of phentolamine mesylate (PT), an alpha-adrenoceptor antagonist. The results show that clinical doses of DEX and PE inhibit DNIC, thereby affecting and modulating the intrinsic pain inhibition system. These findings suggest that adrenergic neurons are involved in DNIC.

The use of ketamine-xylazine and ketamine-medetomidine with and without their antagonists, yohimbine and atipamezole hydrochloride to immobilize Raccoons (<em>Procyon lotor</em>) in Ontario, Canada

This study was undertaken to identify a drug combination that provided a suitable plane of anesthesia and pain suppression and reduced recovery time for minor surgical procedures in raccoons. In fall 2004, 40 wild Raccoons (Procyon lotor) were chemically immobilized using ketamine hydrochloride combined with either xylazine or medetomidine hydrochloride. Immobilizing treatments within and between drug types were compared in terms of induction, arousal and recovery times. The ketamine-xylazine (KX) group (n = 20) was given a combination of 20 mg/kg ketamine hydrochloride and 2 mg/kg xylazine hydrochloride by body weight, and the effects on induction, arousal and recovery time were recorded with and without the antagonist yohimbine hydrochloride. The ketamine-medetomidine (KM) group (n = 20) was given a combination of 5 mg/kg ketamine hydrochloride and 0.05 mg/kg medetomidine hydrochloride by body weight, and induction, arousal and recovery times were recorded with and without the use of the antagonist atipamezole hydrochloride. Administration of yohimbine hydrochloride at 0.1 mg/kg body weight to the KX group and atipamezole hydrochloride at 0.25 mg/kg body weight to the KM group produced considerably shorter arousal and recovery times in the KM group (P = 0.016). Mean arousal and recovery time with standard deviations ± ( SD ) for the KX group with yohimbine hydrochloride antagonist were 36.10 ± 10.69 and 94.2 ± 23.18 minutes; for the KM group with atipamezole hydrochloride antagonist, they were 7.95 ± 3.94 and 65.58 ± 14.75 respectively. At these doses, the KM combination reversed with atipamezole hydrochloride significantly reduced arousal and recovery times and resulted in a quality of anesthesia that would allow safe tooth and blood extraction in Raccoons.

Application of fast-track surgery principles to evaluate effects of atipamezole on recovery and analgesia following ovariohysterectomy in cats anesthetized with dexmedetomidine-ketamine-hydromorphone.

To evaluate the effects of atipamezole hydrochloride on recovery and analgesia following ovariohysterectomy in cats anesthetized with a dexmedetomidine hydrochloride, ketamine hydrochloride, and hydromorphone hydrochloride combination, in accordance with fast-track surgery principles. Prospective, randomized, clinical trial. 44 cats. Cats were anesthetized with a combination of dexmedetomidine (15 μg/kg [6.8 μg/lb]), ketamine (5 mg/kg [2.3 mg/lb]), and hydromorphone (0.05 mg/kg [0.023 mg/lb]), IM, supplemented with isoflurane in oxygen. Immediately after ovariohysterectomy, cats received meloxicam (0.2 mg/kg [0.09 mg/lb]) SC and either atipamezole (75 μg/kg [34.1 μg/lb]) or an equivalent volume of saline (0.9% NaCl) solution IM. Pain and sedation were scored at baseline (prior to surgery) and at predetermined intervals after surgery. Time to sternal recumbency was recorded. The atipamezole group recovered to sternal recumbency faster (median, 15 minutes; range, 5 to 60 minutes) than the saline solution group (median, 60 minutes; range, 15 to 90 minutes]). Pain scores did not differ between groups or at any time, compared with baseline, and were below the intervention threshold for most cats. Sedation scores were significantly greater in the saline solution group (median, 0; range, 0 to 2) at 2 hours after surgery, compared with the atipamezole group (median, 0; range, 0 to 0). Results indicated that administration of atipamezole, compared with saline solution, allowed for a faster recovery from anesthesia with dexmedetomidine-ketamine-hydromorphone in cats following ovariohysterectomy without compromising analgesia. These findings have implications for the provision of appropriate postoperative analgesia following ovariohysterectomy in cats.

The Crystal and Molecular Structure of Atipamezole Base and Atipamezole Hydrochloride

Crystal structures of alpha2-adrenergic antagonist atipamezole base (1) and its hydrochloric acid salt (2) have been determined using X-ray diffraction methods. Atipamezole base crystallized in the monoclinic space group P21, with unit cell parameters a = 13.238(4), b = 9.747(4), c = 14.609(5) A, β = 107.75(4)o, V = 1,795.3(12) A3 and Z = 6 (three independent molecules of 1). Atipamezole hydrochloride crystallized in the monoclinic space group Cc, with unit cell parameters a = 12.052(1), b = 32.561(9), c = 13.668(5) A, β = 102.64(1)o, V = 5,233(2) A3 and Z = 16 (four independent molecules of 2). Each of the three atipamezole moieties in 1 has an intramolecular C–H···N H-bond. In both structures the molecules are H-bonded to form extended chains. Crystal structures of alpha2-adrenergic antagonist atipamezole base and its hydrochloric acid salt have been determined using X-ray diffraction methods.

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

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

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.

Anaesthesia of nyala (Tragelaphus angasi) with a combination of thiafentanil (A3080), medetomidine and ketamine

A combination of thiafentanil (A3080), medetomidine hydrochloride (MED) and ketamine hydrochloride (KET) was evaluated in 19 boma-habituated (12 female and 7 males) and 9 free-ranging nyala (7 male and 2 females) (Tragelaphus angasi) to develop a safe and reliable anaesthesia protocol. Wide dosages were used safely during this study with ranges for A3080 of 45 +/- 8 microg/kg with MED of 69 +/- 19 microg/kg and KET of 3.7 +/- 1.0 mg/kg (200 mg/ animal). The dosages developed on boma-habituated nyala proved to be equally effective in 9 adult free-ranging nyala (7 males and 2 females). The optimum dosage for nyala was a combination of A3080 (40-50 microg/kg), MED (60-80 microg/kg) plus 200 mg of KET/animal. The anaesthesia was characterised by a short induction, good muscle relaxation and mild hypoxaemia during monitoring the anaesthesia was rapidly and completely reversed by naltrexone hydrochloride (30 mg/mg of A3080) and atipamezole hydrochloride (5 mg/mg of MED) given intramuscularly. There was no mortality or morbidity associated with this protocol.

Immobilisation of impala (Aepyceros melampus) with a ketamine hydrochloride/medetomidine hydrochloride combination, and reversal with atipamezole hydrochloride.

A combination of medetomidine hydrochloride (medetomidine) and ketamine hydrochloride (ketamine) was evaluated in 16 boma-confined and 19 free-ranging impalas (Aepyceros melampus) to develop a non-opiate immobilisation protocol. In free-ranging impala a dose of 220 +/- 34 microg/kg medetomidine and 4.4 +/- 0.7 mg/kg ketamine combined with 7500 IU of hyaluronidase induced recumbency within 4.5 +/- 1.5 min, with good muscle relaxation, a stable heart rate and blood pH. PaCO2 was maintained within acceptable ranges. The animals were hypoxic with reduced oxygen saturation and low PaO2 in the presence of an elevated respiration rate, therefore methods for respiratory support are indicated. The depth of sedation was adequate for minor manipulations but additional anaesthesia is indicated for painful manipulations. Immobilisation was reversed by 467 +/- 108 microg/kg atipamezole hydrochloride (atipamezole) intramuscularly, but re-sedation was observed several hours later, possibly due to a low atipamezole:medetomidine ratio of 2:1. Therefore, this immobilisation and reversal protocol would subject impalas to possible predation or conspecific aggression following reversal if they were released into the wild. If the protocol is used on free-ranging impala, an atipamezole:medetomidine ratio of 5:1 should probably be used to prevent re-sedation.

Experimental comparison of ketamine with a combination of ketamine, butorphanol and medetomidine for general anaesthesia of the Eurasian badger ( Meles meles L.)

The refinement of anaesthetic regimes is central to improving the welfare of captured wildlife. The Eurasian badger ( Meles meles) has been the subject of an intensive long-term ecological and epidemiological study at Woodchester Park, Gloucestershire, England. During routine trapping operations (June 21st, 2000–January 23rd, 2001) an experimental trial was conducted on 89 badgers to compare the physiological effects of anaesthesia using ketamine hydrochloride alone, and in conjunction with medetomidine hydrochloride and butorphanol tartrate. The mixture induced a significantly longer period of anaesthesia, and either substantially reduced or eliminated the adverse effects associated with ketamine anaesthesia (e.g., excessive salivation, bouts of sneezing, rough recoveries, and muscle rigidity). In a sub-sample of badgers given the mixture, anaesthesia was reversed using atipamezole hydrochloride. Under ketamine anaesthesia, heart rates were initially significantly higher and respiration rates were consistently higher, than in badgers given the mixture. In all badgers heart rates declined and respiration rates increased during anaesthesia, but the rate of change was greatest in animals given only ketamine. Overall, the mixture provided a more balanced anaesthesia characterised by muscle relaxation and complete unconsciousness.

Immobilization of free-ranging moose (Alces alces) with medetomidine-ketamine and remobilization with atipamezole

Seventeen free-ranging moose {Alces alces) (2 adult males, 13 adult females and 2 female calves) were immobilized with a combination of medetomidine hydochloride (MED) and ketamine hydrochloride (KET) in early autumn (August-September). Drugs were administrated with plastic projectile syringes fired from a dart gun, either from a car or by approaching the animals on foot. MED at 30 mg/adult and 15 mg/calf in combination with KET at 400 mg/adult and 200 mg/calf induced complete immobilization with sternal or lateral recumbency and loss of the corneal reflex in all individuals. The mean ± SD time from darting to when the animals were found was 18.3 ± 8.7 min for adults and the mean distance covered by these animals between darting and recumbency was 320 + 200 m. No side effects of clinical significance were detected and registration of the rectal temperature (38.8 ± 0.5°C), heart rate (44 ± 7 beats/min), respiratory rate (31 ±20 breaths/min) and relative arterial oxygen saturation (89 ± 3 %, n=8) during immobilization in adults showed that these physiological parameters were within the safe ranges established for moose. Blood samples from adults were analyzed for 17 haematological and 33 serum biochemical constituents and the results were compared to corresponding values found in moose immobilized with etorphine (ETO). Although the lower levels (p<0.05) found for haematocrit, red blood cells, haemoglobin and Cortisol in the MED-KET group may indicate a difference in the stress response, the low muscle enzyme levels in both groups show that these immobilizing drugs and capture methods induce very little physical stress in moose. A hyperglycaemic response was found in MED-KET treated animals. Atipamezole hydrochloride (ATI) rapidly remobilized all animals and the time elapsing from ATI administration to standing was 3-9 ± 1.8 min after i.v./s.c. treatment (n=7) and 6.9 ± 3.4 min after i.m./s.c. injection (n=8). No side effects were detected after reversal. In conclusion, medetomidine-ketamine and atipamezole can be recommended for reversible immobilization of free-ranging moose in early autumn.

The effect of xylazine on plasma thromboxane B2 concentration in sheep.

alpha 2-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 alpha 2 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 alpha 2-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 alpha 2-adrenoceptor antagonist.

Buccal delivery of an α2-adrenergic receptor antagonist, atipamezole, in humans*

To evaluate the pharmacokinetics, systemic effects and clinical applicability of buccally administered atipamezole in healthy volunteers. The study was carried out in two parts. In the first part, spray preparations of atipamezole hydrochloride in water/alcohol (50/50) solution were applied on buccal mucosa of six volunteers. Single doses of 5, 10, 20, and 40 mg atipamezole hydrochloride were administered in ascending order during separate sessions. In the second part, nine subjects received single 20 mg doses as buccal spray, intravenous infusion, or oral solution in randomized order. Values for area under the concentration-time curve for atipamezole (mean +/- SD) ranged from 26 +/- 4 ng x hr/ml after 5 mg to 112 +/- 21 ng x hr/ml after 40 mg and peak concentrations ranged from 11 +/- 3 ng/ml after 5 mg to 38 +/- 9 ng/ml after 40 mg. Individual peak concentrations were mainly measured at 30 and 60 minutes after administration. Mean elimination half-lives were approximately 1 1/2 hours after every treatment. In part two, a mean bioavailability of 33% was calculated for buccal administration (compared with intravenous), whereas systemic availability after an oral dose was < 2%. After intravenous administration the mean total clearance, apparent volume of distribution, and elimination half-life were 1.2 L/hr/kg, 2.9 L/kg, and 1.8 hours, respectively. The intravenous administration of 20 mg atipamezole hydrochloride produced a fivefold elevation in mean plasma norepinephrine concentration, a slight and short-lasting elevation in blood pressure and, in most subjects, increased tension, alertness and restlessness, and sweating. After buccal administration, some subjects reported short-lasting restlessness or tension after the 20 and 40 mg doses. No significant changes in heart rate, blood pressure, or plasma catecholamines were observed. No effects were observed after swallowing of 20 mg atipamezole hydrochloride. The spray caused local reactions at buccal mucosa. Superficial white spots or areas were observed for several hours; these disappeared gradually. Subjects also reported transient numbness at the application site. Atipamezole hydrochloride is well absorbed systemically through oral mucosa. The oral bio-availability of atipamezole is negligible, probably because of extensive first-pass metabolism.

Chemical capture of free-ranging red deer (Cervus elaphus) with medetomidine-ketamine

Seventeen free-ranging red deer (Cervus elaphus) (12 calves and 5 yearling hinds) were immobilized with a combination of medetomidine hydrochloride (MED) and ketamine hydrochloride (KET) in winter (January-March). Immobilizations were performed with plastic projectile syringes fired from a dart gun. Mean (SD) doses of 0.147 (0.024) mg MED/kg and 2.5 (0.4) mg KET/kg induced recumbency in 5.0 (2.0) minutes in the calves and all of them were completely immobilized. The initial doses in the yearling hinds were 0.099 (0.016) mg MED/kg and 1.9 (0.2) mg KET/kg but three of them required addirional dosing for induction of reliable restraint. The distance covered by the animals between darting and recumbency ranged from 40-250 m for calves and 100-300 m for yearling hinds. The animals were translocated to deer farms for breeding purposes and were given 12.5-25.0 mg of atipamezole hydrochloride before transportation. All animals recovered completely. Haematological and serum biochemical comparisons between free-ranging calves immobilized with medetomidine-ketamine (n=3) and captive unmedicated calves (n=4) showed that chemical capture induce very little stress in red deer.