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PubMed1989

Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs.

Phencyclidine (PCP), a dissociative anesthetic and widely abused psychotomimetic drug, and MK-801, a potent PCP receptor ligand, have neuroprotective properties stemming from their ability to antagonize the excitotoxic actions of endogenous excitatory amino acids such as glutamate and aspartate. There is growing interest in the potential application of these compounds in the treatment of neurological disorders. However, there is an apparent neurotoxic effect of PCP and related agents (MK-801, tiletamine, and ketamine), which has heretofore been overlooked: these drugs induce acute pathomorphological changes in specific populations of brain neurons when administered subcutaneously to adult rats in relatively low doses. These findings raise new questions regarding the safety of these agents in the clinical management of neurodegenerative diseases and reinforce concerns about the potential risks associated with illicit use of PCP.

Animals↗
PubMed1982

Stereoselective antagonism of phencyclidine's discriminative properties by adenosine receptor agonists.

Rats trained to discriminate between phencyclidine and saline vehicle were used to test various agents for their ability to mimic or block the phencyclidine cue. ketamine, dexoxadrol, tiletamine, and phencyclidine analogs were found to mimic phencyclidine's behavioral effects. Treatment with the adenosime receptor agonists N6-cyclohexyladenosine and L-phenylisopropyladenosine blocked the discriminative properties of phencyclidine. These results suggest that adenosine receptor agonists might be useful in treating phencyclidine-induced psychosis.

Adenosine↗
PubMed1991

Immobilisation of southern elephant seals and leopard seals with cyclohexamine anaesthetics and xylazine.

Ketamine and xylazine were given to 55 southern elephant seals (Mirounga leonina) for stomach lavaging, and to three leopard seals (Hydrurga leptonyx). The elephant seals showed prolonged apnoea and two of them died owing to aspiration of stomach contents. Two of the leopard seals died from unknown causes. Tiletamine and zolazepam were given to five elephant seals and one leopard seal. Two of the elephant seals and the leopard seal died from unknown causes. Xylazine alone was administered to 34 leopard seals. Sedation was poor at low dose rates (less than 1.7 mg/kg) but four of the seals given higher dose rates died owing to the aspiration of stomach contents.

Anesthetics↗
PubMed1980

Thermoregulation in Telazol (CI-744)-anesthetized rhesus monkey (Macaca mulatta).

Seven Telazol (CI-744)-[Telazol is an experimental drug (Parke, Davis) composed of two ingredients in equal amounts by weight: tiletamine HCl, designated chemically as 2-(ethylamino)-2-(2-thienyl)cyclohexanone-HCl, and zolazepam HCl, designated as 4-(o-fluorophenyl)-6,8-dihydro-1,3,8-trimethylpyrazolo-3,4-e 1,4 diazepin-7(IH)-one monohydrochloride] anesthetized rhesus monkeys (Macaca mulatta) were exposed to ambient temperatures (Ta) of 15, 23, 29, 35, and 38 degrees C to evaluate the effect of this dissociative anesthetic agent on thermoregulation. Thermal equilibrium in both anesthetized and control animals at Ta 15 degrees C was through peripheral vasoconstriction and metabolic heat production (M); shivering increased M in the anesthetized group to 1.7 times the resting M of 41.4 W x m-2. Both groups at Ta 38 degrees C regulated body temperature by vasodilation and increased skin evaporative heat loss (Esk) due to sweating. Anesthetized animals increased Esk from 6.4 W x m-2 at Ta 29 degrees C to 32.5 W x m-2 at Ta 38 degrees C. Panting was not observed in either group. Effective tissue thermal conductance was lowest at Ta 15 and 23 degrees C (6.9 and 7.6 W x m2 x degrees C-1, respectively), and increased with Ta's above 23 degrees C (45.0 W x m-2 at Ta 38 degrees C). These results indicate that Telazol-anesthetized monkeys maintain thermal balance at ambient temperatures from 15 to 38 degrees C, and that Telazol induces little or no impairment of thermoregulation in rhesus monkeys.

Anesthesia↗
PubMed1995

Slow and saccadic eye movements evoked by microstimulation in the supplementary eye field of the cebus monkey.

1. Intracortical microstimulation was used to map the supplementary eye field (SEF) in eight hemispheres of five Cebus apella monkeys. Monkeys were immobilized during experiments with Telazol (tiletamine HCl and zolazepam HCl), a dissociative anesthetic agent that was demonstrated to have no significant effect on microstimulation-induced eye movement parameters compared with similar experiments in alert, behaviorally trained monkeys. The functional subregions were defined with the use of low-threshold current (< or = 50 microA). Electrically elicited eye movements were videotaped and quantified. Both slow and saccadic eye movements were reliably evoked at low threshold by microstimulation in each of eight hemispheres studied. The two types of eye movements were clearly distinguished by their significantly different duration and velocity (P < 0.0001) and their different responses to long stimulus trains. The results strongly support the proposal that the SEF produces not only saccadic eye movements as previously reported but also slow (pursuit) eye movements.

Anesthetics↗
PubMed2003

Radiographic and electrocardiographic evaluation of cardiac morphology and function in captive cheetahs (Acinonyx jubatus).

In a prospective study, eight (four males and four females) healthy, adult captive cheetahs (Acinonyx jubatus) were immobilized with a combination of tiletamine-zolazepam (4 mg/kg, i.m.), administered with a remote drug delivery system, to define normal cardiac morphology and function. Standard lateral and ventrodorsal (VD) radiographs were then taken to measure heart and thorax using a metric and vertebral scale system. Standard six-lead electrocardiograms were obtained with the animals in right lateral recumbency under isoflurane anesthesia. Mean chest depth and width was 18.7 +/- 1.3 cm and 13.0 +/- 0.6 cm, respectively. The mean lateral cardiac short axis (X) was 9.1 +/- 0.6 cm. the mean cardiac long axis (Y) was 13.6 +/- 0.7 cm, and the mean lateral heart sum (X + Y) was 22.6 +/- 1.2 cm. In the VD projection, mean cardiac short axis (V) was 10.1 +/- 0.7 cm, mean cardiac long axis (W) was 14.9 +/- 1.2 cm, and the heart sum (V + W) was 24.9 +/- 1.8 cm. The vertebral heart size was 8.2 +/- 0.9. All cheetahs had sinus rhythm, and no arrhythmias were noted. Mean heart rate was 126 +/- 15 beats/min, and the mean electrical axis was 82 + 5 degrees. P waves were always positive on lead II and had a width of 0.04 +/- 0.01 sec and a height between 0.1 and 0.3 mV. PR intervals were 0.11 +/- 0.01 sec. The height of the QRS complex was 1.25 +/- 0.24 mV and the width 0.06 +/- 0.01 sec. The ST segment was 0.04 sec, and the T wave (height: 0.25 +/- 0.05 mV) was positive in all cheetahs examined. Although these cardiac and thoracic measurements were larger than those of domestic cats (Felis catus), ratios of cardiac parameters were similar in both species. Electrocardiographic findings were similar to those reported from domestic cats.

Acinonyx↗
PubMed2004

Four preanesthetic oral sedation protocols for rhesus macaques (Macaca mulatta).

The efficacies and ease of administration of four oral preanesthetic sedation protocols were compared in 18 adult, male rhesus macaques (Macaca mulatta) to achieve heavy sedation and alleviate anxiety, agitation, and potential trauma associated with remote anesthesia induction. The macaques, with average age and weight of 10 yr and 12.5 kg, respectively, were randomly assigned to one of four groups. Group 1 was given 10 mg/kg tiletaminezolazepam and 0.05 mg/kg medetomidine p.o., group 2 was given 1 mg/kg midazolam and 20 mg/kg ketamine p.o., group 3 was given 20 mg/kg ketamine and 0.05 mg/kg medetomidine p.o., and group 4 was given 3 mg/kg midazolam p.o. All protocols produced effects ranging from mild sedation to no response to noxious stimuli, depending on the success of administration. The mean interval to peak effect was 27-43 min in all groups. Ketamine and medetomidine provided significantly better sedation than midazolam alone; there were no other statistically significant differences among the four protocols. Oral tiletamine-zolazepam and medetomidine provided smooth, mild to moderate sedation with few side effects. The midazolam and ketamine combination resulted in severe ataxia. Orally administered ketamine and medetomidine provided smooth, easily reversible, heavy sedation leading to no response to noxious stimuli. Midazolam alone provided only mild sedation. No statistically significant differences in palatability of the four protocols were identified. Orally administered ketamine and medetomidine (group 3) provided the most consistently heavy sedation. A compounding pharmacy may be able to increase the palatability and level of acceptance of these combinations. Alternatively, oral midazolam syrup is well accepted by some animals and provides a mild sedative and calming effect, which may decrease stress associated with the induction of anesthesia via darting, pole syringes, etc.

Administration, Oral↗
PubMed2000

Evaluation of semen collected by electroejaculation from captive lesser Malay chevrotain (Tragulus javanicus).

Thirteen sexually mature captive male lesser Malay chevrotains (Tragulus javanicus) were each anesthetized twice with tiletamine-zolazepam for electroejaculation. Viable spermatozoa were collected from all animals. The semen was creamy, milky, pale yellowish, or watery. The mean values for ejaculate volume, sperm concentration, and percentages of sperm motility, normality and viability were 23.7 +/- 2.5 microl, 366.9 +/- 127.8 x 10(6) spermatozoa/ml, 40.0% +/- 3.1%, 71.4% +/- 1.6%, and 59.6% +/- 2.1%, respectively. Semen pH was 7-8. No adverse effects of electroejaculation were noted. These are the first reported values for semen of lesser Malay chevrotain. Electroejaculation should be usable for routine semen collection in this species.

Anesthetics, Dissociative↗
PubMed2000

Anesthetic, cardiorespiratory, and metabolic effects of four intravenous anesthetic regimens induced in horses immediately after maximal exercise.

OBJECTIVE: To determine the anesthetic, cardiorespiratory, and metabolic effects of 4 IV anesthetic regimens in Thoroughbred horses recuperating from a brief period of maximal exercise. ANIMALS: 6 adult Thoroughbreds. PROCEDURE: Horses were preconditioned by exercising them on a treadmill. Each horse ran 4 simulated races, with a minimum of 14 days between races. Races were run at a treadmill speed that caused horses to exercise at 120% of their maximal oxygen consumption. Horses ran until fatigued or for a maximum of 2 minutes. Two minutes after exercise, horses received a combination of xylazine hydrochloride (2.2 mg/kg of body weight) and acepromazine maleate (0.04 mg/kg) IV. Five minutes after exercise, horses received 1 of the following 4 IV anesthetic regimens: ketamine hydrochloride (2.2 mg/kg); ketamine (2.2 mg/kg) and diazepam (0.1 mg/kg); tiletamine hydrochloride-zolazepam hydrochloride (1 mg/kg); and guaifenesin (50 mg/kg) and thiopental sodium (5 mg/kg). Treatments were randomized. Cardiopulmonary indices were measured, and samples of blood were collected before and at specific times for 90 minutes after each race. RESULTS: Each regimen induced lateral recumbency. The quality of induction and anesthesia after ketamine administration was significantly worse than after other regimens, and the duration of anesthesia was significantly shorter. Time to lateral recumbency was significantly longer after ketamine or guaifenesin-thiopental administration than after ketaminediazepam or tilet-amine-zolazepam administration. Arterial blood pressures after guaifenesin-thiopental administration were significantly lower than after the other regimens. CONCLUSIONS AND CLINICAL RELEVANCE: Anesthesia can be safely induced in sedated horses immediately after maximal exercise. Ketamine-diazepam and tilet-amine-zolazepam induced good quality anesthesia with acceptable perturbations in cardiopulmonary and metabolic indices. Ketamine alone and guaifenesin-thiopental regimens are not recommended.

Acepromazine↗
PubMed2000

Comparison of four drug combinations for total intravenous anesthesia of horses undergoing surgical removal of an abdominal testis.

OBJECTIVE: To evaluate anesthetic effects of 4 drug combinations used for total intravenous anesthesia of horses undergoing surgical removal of an abdominal testis. DESIGN: Clinical trial. ANIMALS: 32 healthy cryptorchid horses. PROCEDURE: Horses were sedated with xylazine and butorphanol and were randomly assigned to 1 of 4 groups: induction of anesthesia with ketamine and diazepam and maintenance with bolus administration of ketamine and xylazine (KD/KX); induction and maintenance of anesthesia with bolus administration of tiletamine-zolazepam, ketamine, and detomidine (TKD); induction and maintenance of anesthesia with continuous infusion of xylazine, guaifenesin, and ketamine; and induction and maintenance of anesthesia with continuous infusion of guaifenesin and thiopental. Horses that moved 3 consecutive times in response to surgical stimulation or for which surgery time was > 60 minutes were administered an inhalant anesthetic, and data from these horses were excluded from analysis. RESULTS: Quality of induction was not significantly different among groups. Muscle relaxation and analgesia scores were lowest for horses given KD/KX, but significant differences among groups were not detected. Horses anesthetized with TKD had a significantly greater number of attempts to stand, compared with the other groups, and mean quality of recovery from anesthesia for horses in the TKD group was significantly worse than for the other groups. Anesthesia, surgery, and recovery times were not significantly different among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that all 4 drug combinations can be used to induce short-term anesthesia for abdominal cryptorchidectomy in horses. However, horses receiving TKD had a poorer recovery from anesthesia, often requiring assistance to stand.

Adrenergic alpha-Agonists↗
PubMed1996

Field immobilization of Ethiopian wolves (Canis simensis).

Telazol (tiletamine hydrochloride and zolazepam hydrochloride combination) and a combination of ketamine hydrochloride and acepromazine were used to immobilize wild Ethiopian wolves (Canis simensis) in Ethiopia from 1988 to 1992. Telazol doses of 2.1 to 6.5 mg/kg resulted in a mean (+/- SD) induction time of 2.3 +/- 0.9 min and a mean (+/- SD) immobilization time of 82.2 +/- 28.6 min. Induction time did not differ by dose, wolf weight, or age, but was significantly longer for females. Immobilization time differed with dose, but not by wolf weight, age, or sex. Total recovery times ranged from 50 to 158 min. There were no apparent side effects on immobilized animals. Wolves immobilized using a combination of ketamine hydrochloride and acetylpromazine had longer induction time (3.0 +/- 0.8 min) and recovery time (114.7 +/- 29.2 min). Telazol is an effective and safe agent for immobilizing Ethiopian wolves and is preferred to ketamine/acetylpromazine.

Acepromazine↗
PubMed2000

A Zoletil-Rompun mixture as an alternative to the use of opioids for immobilization of feral red deer.

Sixty chemical immobilizations of red deer (Cervus elaphus hippelaphus) have been carried out during an etho-ecological study from August 1994 to December 1996 in a 35 ha pen in the district of Nitra (Slovac Republic). Our objective was to determine the efficacy and standard dosages of Zoletil and Rompun for the immobilization of adult red deer in feral conditions as an alternative to the use of the highly toxic opioids. We therefore compared an Immobilon-Rompun combination (ImRo) with a 1:1 mixture of Zoletil and Rompun (ZoRo) as an injectable solution. Use of both combinations led to the immobilization of >92% of deer with an injection volume <3 ml. Mean (SD) dose to achieve immobilization was 35 (14) microg/kg ethorphine + 0.14 (0.056) mg/kg acepromazine + 0.36 (0.14) mg/kg xylazine compared to 1.2 (0.8) mg/kg tiletamine + 1.2 (0.8) mg/kg zolazepam + 2.3 (1.6) mg/kg xylazine. This corresponds to a volume of 1.8 (0.7) ml/100 kg body mass (BM) for ImRo (range = 1.0 to 4.6) and to 2.3 (1.6) ml/100 kg BM for ZoRo (range = 0.7 to 4.0), respectively. Heart rate, respiratory rate and oxyhaemoglobin saturation values did not differ significantly between the two groups during immobilization. Three deer (5%) died during immobilization, but fatalities could not be directly associated with the drug effect. Mean (SD) time from darting to complete immobilization was 5.5 (4.2) min for ImRo and 7.5 (6.1) min for ZoRo, respectively. Differences were not statistically significant. Anesthesia with both combinations of immobilizing agents could be reversed within 2 min using sarmazenile-yohimbine for ZoRo and diprenorphine-yohimbine for ImXy immobilizations, respectively. We conclude that the 1:1 combination of Zoletil and xylazine is a valuable alternative to the use of opioids for the immobilization of adult red deer including feral adult animals.

Acepromazine↗
PubMed2003

Evaluation of three combinations of anesthetics for use in free-ranging alpine marmots (Marmota marmota).

From April 1998 to September 2000, 241 free-ranging alpine marmots (Marmota marmota) were anesthetized in the course of a field project using either xylazine plus ketamine (XK), medetomidine plus ketamine (MK), or xylazine plus a 1:1 mixture of zolazepam and tiletamine (XZT). For each of the combinations, the respective doses for short term and long-term surgery were established and seasonal variations in the amount of drugs needed were assessed. No fatalities occurred, and doses for efficient and safe anesthesia in spring were as follows (XK, MK, and XZT, respectively, in mg/kg body mass): short term surgery 3 + 40, 0.25 + 35, and 3 + 15; long term surgery 20 + 80, 0.5 + 70, and 10 + 20. In late summer/autumn, higher doses (20 + 60, 0.2 + 60, and 10 + 15 for short term surgery) had to be administered, probably due to increase of marmots' body fat content. Heart rate, respiratory rate, rectal temperature, palpebral reflex, muscle relaxation, and analgesia were monitored to evaluate the animals' responses to each of the drug combinations. Hypothermia was induced by all combinations and heart rate significantly decreased during anesthesia, especially in marmots receiving MK. Respiratory rate was highly variable and no significant differences between the drugs were found. Muscle relaxation was rather poor in marmots anesthetized with XK. The XZT combination tended to have a longer induction period but was found to subsequently depress the palpebral reflex and induce muscle relaxation and analgesia very efficiently. We conclude that, regardless of the anesthetics used, doses should always be adjusted to the planned manipulations, the marmots' nutritional state, and to the time of year. Furthermore, close monitoring of physiologic parameters, especially body temperature, should be guaranteed. On the basis of physiologic and behavioral responses, XZT is the most effective drug combination for anesthetizing alpine marmots, especially for long term, potentially painful procedures.

Anesthesia↗
PubMed2003

A comparison of carfentanil/xylazine and Telazol/xylazine for immobilization of white-tailed deer.

October 2001 to January 2002, captive free-ranging white-tailed deer (Odocoileus virginianus) were immobilized with a combination of carfentanil citrate and xylazine hydrochloride. From this study, we selected a dose of carfentanil/xylazine for the purpose of comparing immobilization parameters and physiologic effects with those of a combination of tiletamine and zolazepam (Telazol) and xylazine. Animals were initially given intramuscular injections of 10 mg xylazine and one of four doses of carfentanil (i.e., 0.5, 1.0, 1.5, and 2.0 mg). A carfentanil dose of 1.2 mg (x +/- SD = 23.5 +/- 3.2 microg/kg) and 10 mg xylazine (0.2 +/- 0.03 mg/kg) were selected, based on induction times and previously published reports, to compare with a combination of 230 mg of Telazol (4.5 +/- 0.6 mg/kg) and 120 mg xylazine (2.3 +/- 0.3 mg/kg). Time to first observable drug effects and to induction were significantly longer for deer treated with carfentanil/xylazine than with Telazol/xylazine (P < 0.01). Hyperthermia was common in deer immobilized with carfentanil/xylazine, but heart rate, respiration rate, and hemoglobin saturation were within acceptable levels. Degree of anesthesia of deer immobilized with Telazol/xylazine was superior to deer immobilized with carfentanil/xylazine. The combination of 120 mg of naltrexone hydrochloride and 6.5 mg of yohimbine hydrochloride provided rapid and complete reversal (1.9 +/- 1.1 min) of carfentanil/xylazine immobilization. Animals immobilized with Telazol/xylazine had long recovery times with occasional resedation after antagonism with 6.5 mg of yohimbine. The combination of carfentanil and xylazine at the doses tested did not provide reliable induction or immobilization of white-tailel (leer even though drug reversal was rapid and safe using naltrexone and yohimbine.

Adrenergic alpha-Agonists↗
PubMed2004

Comparative immobilization of wild felids in Thailand.

We immobilized individuals of four free-ranging felid species, leopard cat (Prionailurus bengalensis), clouded leopard (Neofelis nebulosa), Asiatic golden cat (Catopuma temminckii), and marbled cat (Pardofelis marmorata) with ketamine hydrochloride and xylazine hydrochloride (KH-XH) and with tiletamine hydrochloride and zolazepam hydrochloride (TH-ZH) between March 1998 and July 2002. Mean (+/-SD) dose of KH and XH was 26.51+/-5.71 mg/kg and 1.89+/-0.43 mg/kg, respectively (n=25), and mean dose of TH-ZH was 11.61+/-3.39 mg/kg (n=28). Dose was significantly correlated with induction time (P<0.001) and duration of anesthesia (P<0.05), but not with recovery time. There were significant differences between the drug combinations in time to induction (P<0.03) and time to anesthesia (P<0.01); recovery times were not significantly different. We conclude that immobilization of these felids with TH-ZH and KH-XH is effective and safe, but TH-ZH is preferred because of the smaller volume of drug necessary for sedation, faster time to induction, and absence of prolonged muscle rigidity during anesthesia.

Adrenergic alpha-Agonists↗
PubMed2004

Field immobilization of raccoons (Procyon lotor) with Telazol and xylazine.

The effectiveness of tiletamine plus zolazepam (Telazol) and xylazine was evaluated as an immobilizing combination for raccoons (Procyon lotor). Fifteen raccoons were injected intramuscularly with a 3:2 mixture of Telazol (3.2+/-0.6 mg/kg [mean+/-SD]) and xylazine (2.1+/-0.4 mg/kg) at Pictured Rocks National Lakeshore, Michigan, USA, during May-October, 2001-03. Mean induction time was 4.8+/-3.8 min; mean recovery time was 128.5+/-48.4 min. No linear relationships were found between the amount (mg/kg) of Telazol-xylazine injected and induction (r2 = 0.06, P = 0.40) or recovery times (r2 = 0.01, P = 0.78). Mean heart rate, respiratory rate, and body temperature declined through 20 min after induction (P< 0.05). No mortality occurred and no short-term adverse effects were observed in recaptured individuals. I conclude that a 3:2 mixture of Telazol-xylazine is a safe and effective immobilizing agent for raccoons when conducting nonsurgical field procedures. Immobilizing raccoons with Telazol at 3 mg/kg and xylazine at 2 mg/kg should provide up to 60 min of handling time and usually allow full recovery in about 120 min.

Adrenergic alpha-Agonists↗
PubMed2001

Optimization of intraperitoneal injection anesthesia in mice: drugs, dosages, adverse effects, and anesthesia depth.

PURPOSE: The goals of the study were to find a safe intraperitoneal injection anesthesia protocol for medium-duration surgery in mice (e.g., embryo transfer/vasectomy) coupled with a simple method to assess anesthesia depth under routine laboratory conditions. METHODS: Eight anesthetic protocols consisting of combinations of dissociative anesthetics (ketamine, tiletamine), alpha2-agonists (xylazine, medetomidine), and/or sedatives (acepromazine, azaperone, zolazepam) were compared for their safety and efficacy (death rate, surgical tolerance), using observations and reflex tests. The four best protocols were further evaluated during vasectomy: physiologic measurements (respiratory rate, electrocardiogram, arterial blood pressure, body temperature, blood gas tensions, and acid-base balance) were used to characterize the quality of anesthesia. The reactions of physiologic parameters to surgical stimuli were used to determine anesthesia depth, and were correlated with reflex test results. RESULTS: The protocol with the highest safety margin and the longest time of surgical tolerance (54 min) was ketamine/ xylazine/acepromazine. Three further anesthetic combinations were associated with surgical tolerance: ketamine/ xylazine, ketamine/xylazinelazaperone, and tiletamine/xylazine/zolazepam (Telazol/xylazine). The protocols consisting of ketamine/medetomidine and ketamine/azaperone were not associated with clearly detectable surgical tolerance. The most reliable parameter of surgical tolerance under routine laboratory conditions was the pedal withdrawal reflex. CONCLUSIONS: The best intraperitoneal injection anesthesia regimen consisted of ketamine/xylazine/acepromazine. The dose must be adapted to the particulars of each experimental design (mouse strain, sex, age, mutation). This is best done by measuring surgical tolerance, using the pedal withdrawal reflex.

Acepromazine↗